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Last Updated: 3/25/2015  

Coronary Heart Disease

Prevention
  • Identify asymptomatic persons at high risk for coronary morbidity and mortality.

  • Modify risk factors for ASCVD, including diabetes mellitus, hypertension, dyslipidemia, obesity, physical inactivity, poor dietary habits, excessive alcohol consumption, and tobacco use.

  • Consider the use of aspirin for primary and secondary prevention in individuals at high risk for ASCVD events.

Screening
  • Do not screen for CHD in asymptomatic persons except in special circumstances.

Diagnosis
  • Use a risk stratification approach based on the estimated pretest probability of CAD.

  • Use exercise electrocardiographic testing as a primary modality in individuals with low pretest probabilities for CAD.

  • Consider the addition of stress radionuclide imaging, stress echocardiography, and invasive coronary angiography in individuals with higher pretest probabilities for CAD.

  • Consider additional testing to evaluate for causes of chest pain other than CAD and to look for cardiac and extracardiac conditions that can produce secondary angina in the absence of significant CAD.

Consultation
  • Consider consulting a cardiovascular disease specialist in the following settings: indeterminate results or high-risk features on noninvasive testing, new onset or newly recognized HF, new onset atrial fibrillation, ventricular arrhythmias, acute coronary syndromes, including MI, refractory angina, and survivors of sudden cardiac arrest.

Hospitalization
  • Evaluate and treat all patients with acute coronary syndromes in a monitored setting.

Therapy
  • Prescribe aspirin and/or dual antiplatelet therapy in all patients with CAD.

  • Implement risk-factor modification as recommended for prevention.

  • Use β-blockers, ACE inhibitors, or ARB therapy and calcium channel blockers as first-line antihypertensives.

  • Consider high-intensity statin therapy in individuals with CAD.

  • Treat angina medically with β-blockers, calcium channel blockers, and long-acting nitrates, and consider the addition of ranolazine in refractory cases.

  • Treat conditions producing secondary angina, such as anemia and HF.

  • Consider coronary revascularization in high-risk patients: those with left-main stenosis, three-vessel CAD, and low LVEF; sudden cardiac arrest survivors; and those with angina refractory to medical therapy.

  • Consider the addition of mineralocorticoid receptor antagonists and/or digitalis glycosides to existing therapy with β-blockers and ACE or ARB therapy in patients with CAD and CHF.

  • Refer specific subsets of patients with CAD and LVEF less than 40% for ICD or CRT implantation.

  • Refer patients with CAD and angina, acute coronary syndromes, and ischemic cardiomyopathy for cardiopulmonary rehabilitation.

  • Provide ongoing patient education, monitor for changes in clinical condition, and continue risk-factor modification during all follow-up visits.

Recommend smoking cessation to all active smokers, and advise limitation of exposure to secondhand smoke. 
  • Inquire about smoking status and exposure to secondhand smoke in all patients.

  • At each visit, quantify tobacco use and estimate secondhand smoke exposure.

  • Use the following approach to encourage smoking cessation, and provide psychological and pharmacologic support to all patients who want to quit smoking in the primary care setting:

    • Systematically identify all tobacco users.

    • Recommend smoking cessation at each visit to patients who smoke.

    • Identify patients who are willing to attempt to quit smoking.

    • Assist patients with the development of a cessation plan.

    • Encourage nicotine replacement or bupropion unless contraindicated.

    • Schedule follow-up contact (in person or by telephone).

  • See module Smoking Cessation.

Evidence
  • A 2013 meta-analysis of physician advice vs. standard care for smoking cessation included 42 RCTs from 1972 to 2012 involving 31,000 smokers. The analysis showed significant increases in quitting rates using simple advice (RR, 1.66 [CI, 1.42 to 1.94]) and intensive advice (RR, 1.37 [CI, 1.20 to 1.56]) (1).

  • A 1999 meta-analysis of 18 cohort and case-control studies showed that nonsmokers exposed to environmental smoke had an increased risk for CHD (RR, 1.25 [CI, 1.17 to 1.32]) compared with nonsmokers not exposed to smoke (2).

  • A population-based, prospective cohort study of 216,917 adults in the United States from 1997 to 2004 showed that smoking significantly increased the risk for death from ischemic heart disease in both women (HR, 3.5 [99% CI, 2.7 to 4.6]) and men (HR, 3.2 [99% CI, 2.5 to 4.1]) compared with nonsmokers. Smoking cessation at age 25 to 34, 35 to 44, 45 to 54, and 55 to 64 years resulted in a gain of 10, 9, 6, and 4 years of life, respectively. However, a small excess risk for mortality from ever having smoked persisted after cessation (3).

Rationale
  • Cigarette smoking and exposure to secondhand smoke are among the leading modifiable causes of cardiac death in the United States.

Comments
  • A clinical practice guideline for treating tobacco use and dependence has been published by the Agency for Healthcare Research and Quality (4).

  • Three RCTs in primary prevention of cardiovascular disease showed that smoking cessation reduced cardiac events by 7% to 47% (5; 6; 7).

  • A 1989 review article indicated that physician counseling against smoking is cost-effective (8).

Prescribe statins to individuals at high risk for ASCVD events. 
  • Measure a fasting lipid panel to determine the need for and intensity of statin therapy in individuals between ages 20 to 79 years who are not taking statins.

  • Start statin therapy in individuals with any of the following:

    • LDL cholesterol level ≥190 mg/dL (screen for genetic hyperlipidemias)

    • Diabetes mellitus with LDL cholesterol level between 70 to 190 mg/dL

    • LDL cholesterol level between 70 and 190 mg/dL, with a 10-year ASCVD risk 7.5% or greater

  • Consider statin therapy in persons with an LDL cholesterol level between 70 and 190 mg/dL, with a 10-year ASCVD risk score between 5% and 7.5%, after an informed discussion about the risk-benefit ratio.

  • Prescribe high-intensity statin therapy (atorvastatin, 40 to 80 mg/d, or rosuvastatin, 10 to 20 mg/d) unless limited by intolerance or other extenuating factors such as age.

  • Know that the selection of statin dose or titration of statin intensity based on LDL cholesterol is not recommended.

  • See module Lipid Disorders.

Evidence
  • A 2013 ACC/AHA guideline on the assessment of cardiovascular risk stated that it is reasonable to assess cardiovascular risk factors, including cholesterol level, every 4 to 6 years in adults age 20 to 79 years who do not have known cardiovascular disease (9).

  • A 2010 Cholesterol Treatment Trialists' Collaboration meta-analysis of data from 170,000 patients across 26 RCTs of statins for primary and secondary prevention showed an overall proportional risk reduction in major vascular events (coronary death, nonfatal infarction, coronary revascularization, and ischemic stroke) of 25% (99% CI, 18 to 31; P<0.0001) per 1.0 mmol/L reduction in LDL cholesterol in participants with no previous history of vascular disease. The study also showed significant reductions of 17% (99% CI, 10 to 24; P<0.0001) among women and of 16% (99% CI, 3 to 27; P=0·002) among people older than 75 years at entry. There was no LDL cholesterol level below which risk reduction was not seen. Taking all 26 trials together, there was a proportional reduction in all-cause mortality of 10% (CI, 7 to 13; P<0.0001) per 1.0 mmol/L reduction in LDL cholesterol level, which consisted of a highly significant reduction in vascular mortality of 14% (CI, 10 to 18; P<0.0001) and a marginally significant reduction in mortality from unknown causes of 13% (CI, 1 to 24; P=0.04), with no apparent effect on nonvascular mortality (RR, 0.97 [CI, 0.92 to 1.03; P=0.3). Analysis of more vs less intensive statin therapy showed further reduction in LDL cholesterol levels by approximately 19 mg/dL, with a reduction in major vascular events by 15% and separate significant reductions in coronary death and nonfatal MI (P<0.0001), coronary revascularization (P<0001), and ischemic stroke (p=0.005) (10).

Rationale
  • Hyperlipidemia is an important modifiable risk factor for the development and progression of ASCVD.

Comments
  • Existing data do not support the titration of lipid-lowering therapy based on LDL cholesterol levels (as previously recommended by 2002 NCEP Adult Treatment Panel III guidelines) (11) but do show that high-intensity statin therapy is better than low-intensity statin therapy.

  • During treatment, obtaining periodic lipid panels may be useful for assessing patient adherence to statin therapy.

  • No benefit of statin therapy has been documented in patients on hemodialysis and patients with advanced HF.

  • The efficacy of statin therapy in patients with solid organ transplants and HIV infection is unclear, given the lack of data on hard long-term outcomes from existing clinical trials.

Identify and treat hypertension to a goal blood pressure of less than 140/90 mm Hg for most patients younger than 60 years.  
  • Routinely measure blood pressure in asymptomatic persons during office visits.

  • Initiate lifestyle modifications in hypertensive patients with an average blood pressure of 140 to 159 mm Hg systolic and 90 to 99 mm Hg diastolic (stage I hypertension) in order to lower blood pressure, and consider one-drug therapy if this fails.

  • Initiate lifestyle modifications and concomitant drug therapy with a two-drug regimen in hypertensive patients with an average blood pressure of >160 mm Hg systolic and >100 mm Hg diastolic (stage II and higher), as follows:

    • Use ACE inhibitors, ARBs, thiazide diuretics, or calcium-channel blockers as first-line agents in non-black patients, including those with diabetes.

    • Use calcium-channel blockers or thiazide diuretics as first-line agents in black patients.

    • Use ACE inhibitor or ARB therapy as first-line antihypertensive agents in patients with diabetes mellitus or chronic kidney disease.

  • Modify selection of antihypertensive agents from guideline recommendations based on patient-specific contraindications to classes of medications.

  • Treat to a goal blood pressure of <140/90 mm Hg in patients age 18 to 59 years and a goal of <150/90 mm Hg in patients age 60 years or older.

  • See module Essential Hypertension.

Evidence
  • A 2014 guideline from the JNC 8 panel members recommended a target blood pressure of <140/90 mm Hg for patients younger than 60 years and <150/90 mm Hg for patients age 60 years or older, regardless of the presence of diabetes. The guideline recommended using ACE inhibitors, ARBs, calcium-channel blockers, or thiazide diuretics as first-line agents in diabetic and nondiabetic, non-black populations, and recommended calcium-channel blockers and thiazide diuretics as first-line agents in diabetic and nondiabetic black patients (12).

  • A 2013 ACC/AHA science advisory on an effective approach to controlling high blood pressure recommended initiation of lifestyle modifications before adding one-drug therapy in patients with stage I hypertension and directly initiating two-drug therapy along with lifestyle modification in patients with stage II hypertension and higher (13).

  • A 2013 guideline from the European Society of Hypertension and the European Society of Cardiology on the management of arterial hypertension recommended initial therapy with thiazide diuretics, calcium-channel blockers, ACE inhibitors, ARB therapy, or β-blockers, and stated that choice of therapy should depend on individual patient factors (14).

  • A 2011 NICE guideline on the clinical management of primary hypertension in adults recommended using an ACE inhibitor or ARB as the first-line agent in patients younger than 55 years, using a calcium-channel blocker as the first-line agent in patients of African or Caribbean descent and in patients older than 55 years, and using a combination of an angiotensin and a calcium-channel blocker in patients requiring more than one drug. The guideline recommended thiazide diuretics, such as chlorthalidone or indapamide, as third-line agents (15).

  • A 2012 systematic review of β-blockers compared with other therapies for hypertension included 13 randomized trials comparing β-blockers with placebo or other agents. Most studies used atenolol. Compared with placebo, β-blockers reduced total cardiovascular disease (RR, 0.88 [CI, 0.79 to 0.97]) and stroke (RR, 0.80 [CI, 0.66 to 0.96]) but not cardiac events. Compared with calcium-channel blockers, β-blockers were associated with a higher risk for cardiovascular disease (RR, 1.18 [CI, 1.08 to 1.29]) and stroke (RR, 1.24 [CI, 1.11 to 1.40]). Compared with angiotensin agents, β-blockers were associated with a higher risk for stroke (RR, 1.30 [CI, 1.11 to 1.53]) but an equivalent risk for cardiovascular disease. Diuretics and β-blockers did not differ in rates of clinical outcomes. Patients on β-blockers were more likely than those on angiotensin agents to discontinue drug use due to adverse events (RR, 1.14 [CI, 1.29 to 1.54]), but discontinuation rates compared with diuretics and calcium-channel blockers were similar (16).

  • A 2009 systematic review of the effect of blood pressure-lowering medications in the prevention of cardiovascular disease included 147 studies. Overall, in patients without known preexisting heart disease, each 10 mm Hg reduction in systolic blood pressure or 5 mm Hg reduction in diastolic blood pressure led to a reduction in CHD events (RR, 0.78 [CI, 0.73 to 0.83]) and strokes (RR, 0.59 [CI, 0.52 to 0.57]) (17).

Rationale
  • Treatment of hypertension significantly reduces the risk for primary cardiovascular events.

Comments
  • Review blood pressure readings every 2 to 4 weeks after initiation of a new drug, and continue clinic visits as otherwise appropriate once adequate control has been achieved.

  • Screening for secondary etiologies is recommended in patients with onset at young ages, accelerated or uncontrolled hypertension despite adequate dosing of three antihypertensive medications including one diuretic, hypertension with rapidly progressing end-organ damage, or recurrent episodes of flash pulmonary edema or CHF.

Test patients for diabetes mellitus according to existing guidelines. 
  • Screen for diabetes mellitus individuals of any age with obesity and one additional risk factor:

    • Physical inactivity

    • First-degree relative with diabetes

    • High-risk ethnicity (black, Asian American, Pacific Islander)

    • Delivery of a baby >9 lb

    • Hypertension

    • Dyslipidemia

    • Polycystic ovarian syndrome

    • ASCVD

    • Previously diagnosed A1C level higher than 5.7% or IFG/IGT

    • Other conditions associated with insulin resistance

  • Screen routinely for diabetes mellitus in all individuals beginning at age 45 years, looking for one or more of the following results:

    • Random plasma glucose level >200 mg/dL in individuals with symptoms of diabetes mellitus or those presenting with a hyperglycemic crisis

    • 2-hour oral glucose tolerance test plasma glucose level >200 mg/dL

    • Fasting plasma glucose level >126 mg/dL

    • Measurement of hemoglobin A1C level higher than 6.5%

  • See module Diabetes Mellitus, Type 2.

Evidence
  • A 2014 ADA guideline on the standards of care in diabetes provided recommendations for screening and treatment of individuals with diabetes mellitus (18).

  • A population study involving all 3.3 million individuals older than 30 years in Denmark showed that patients with diabetes exhibited a risk for ASCVD events comparable to that of patients with known ASCVD, regardless of increasing age or specific sex. Regardless of age, age-adjusted Cox proportional-hazard ratios for cardiovascular death were 2.42 (CI, 2.35 to 2.49) in men with diabetes mellitus without a previous MI and 2.44 (CI, 2.39 to 2.49) in nondiabetic men with a previous MI (P=0.60), with nondiabetics without a previous MI as the reference. Results for women were 2.45 (CI, 2.38 to 2.51) and 2.62 (CI, 2.55 to 2.69) (P=0.001), respectively. For the composite of MI, stroke, and cardiovascular death, the HRs in men with diabetes only were 2.32 (CI, 2.27 to 2.38) and 2.48 (CI, 2.43 to 2.54) in those with a previous MI only (P=0.001). Results for women were 2.48 (95% CI, 2.43 to 2.54) and 2.71 (95% CI, 2.65 to 2.78) (P=0.001), respectively (19).

Rationale
  • Persons with diabetes are at an elevated risk for the development of ASCVD, which is the major cause of morbidity and mortality for individuals with diabetes. The common conditions associated with diabetes (e.g., hypertension and dyslipidemia) are additional risk factors for ASCVD and contribute to a further rise in ASCVD incidence in diabetics. Numerous studies have shown the efficacy of aggressively controlling individual cardiovascular risk factors in preventing or slowing ASCVD in people with diabetes.

Comments
  • A cohort study analyzing Framingham Heart Study participants showed that while the incidence of ASCVD events among diabetic individuals decreased over time, they remained at higher risk for mortality, specifically cardiovascular mortality, compared with individuals without diabetes (HR, 2.44; P<0.0001, for the cohort 1950-1975) and later (HR, 1.95; P<0.0001, for the cohort 1976-2001) (20).

  • A cohort study involving 1373 nondiabetic and 1059 diabetic patients found that the 7-year incidence of MI among diabetic patients without previous MI was as high as the incidence of MI among nondiabetic patients with a history of previous MI (20.2% vs. 18.8%) (21).

Consider primary prevention with aspirin for patients at high risk for ASCVD.  
  • Do not prescribe aspirin for primary prevention in patients at low risk for ASCVD events.

  • Individualize the decision to start aspirin at a dose of 81 mg/d for primary prevention of ASCVD events in high-risk patients by balancing the antithrombotic benefit versus the bleeding risk.

  • Recognize that patients at higher risk for ASCVD events are also often at higher risk for bleeding.

  • For secondary prevention, see Therapy.

Evidence
  • A 2012 meta-analysis of the effect of aspirin on vascular and nonvascular outcomes included 102,621 patients in 9 RCTs of aspirin for primary prevention at doses ranging from 75 mg/d to 500 mg/d. The analysis showed that aspirin use led to a 10% reduction in risk for total ASCVD events (OR, 0.90 [CI, 0.85 to 0.96]), driven by a 20% reduction in risk for nonfatal MI (OR, 0.80 [CI, 0.67 to 0.96]). There was no decrease in fatal MI (OR, 1.06 [CI, 0.83 to 1.37]), stroke (OR, 0.94 [CI, 0.84 to 1.06]), or cardiac death (OR, 0.99 [CI, 0.85 to 1.15]). Of note, there was a 70% excess risk for total bleeding events (OR, 1.70 [CI, 1.17 to 2.46]) and an approximately 30% excess risk for major bleeding, including fatal bleeding, intracranial bleeding, bleeding from hollow organs, and bleeding requiring hospitalization and/or transfusions (OR, 1.31 [CI, 1.14 to 1.50]) (22).

  • A 2009 Antithrombotic Trialists' Collaboration meta-analysis of aspirin for the primary and secondary prevention of vascular disease included 95,000 low-risk patients in 6 primary prevention trials and 17,000 high-risk patients in 16 secondary prevention trials. Aspirin use for primary prevention resulted in a 12% proportional reduction in serious vascular events (0.51% aspirin vs 0.57% control per year; P=0·0001), driven by a reduction in nonfatal MI (0.18% vs 0.23% per year; P<0·0001). The net effect on stroke and death was not significant. Vascular mortality did not differ significantly (0.19% vs 0.19% per year; P=0.7). Aspirin increased major GI and extracranial bleeds (0.10% vs 0.07% per year; P<0.0001). The main risk factors for coronary disease were also risk factors for bleeding (23).

  • A 2009 meta-analysis from the USPSTF found that aspirin use in women was associated with statistically significant reductions in cardiovascular events (OR, 0.88 [CI, 0.79 to 0.99]) and ischemic strokes (OR, 0.76 [CI, 0.63 to 0.93]), but no significant benefit in MIs or cardiovascular mortality. In men, aspirin use was associated with a significant reduction in cardiovascular events (OR, 0.86 [CI, 0.78 to 0.94]) and MIs (OR, 0.68 [CI, 0.54 to 0.86]), but no significant benefit in ischemic strokes or cardiovascular mortality. Total mortality was not significantly reduced by aspirin use in men or women (24).

  • A 2007 systematic review of aspirin dose for the prevention of cardiovascular disease showed no enhanced efficacy of aspirin above the dose of 81 mg/d but an increased rate of bleeding due to GI toxicity (25).

  • In a 1994 meta-analysis of 145 randomized trials, treatment of patients with known coronary or vascular disease using medium-dose aspirin (75 to 325 mg daily) was associated with a 27% reduction in the OR for major cardiovascular events over 5 years. The ARR was 3.3%, corresponding to an NNT of 33 (26).

Rationale
  • Aspirin inhibits platelet activation by irreversible inhibition of the COX-1 enyzme and decreases the risk for platelet thrombi formation in the circulation.

  • By the same mechanism, aspirin also increases the risk for fatal and nonfatal bleeding.

Comments
  • The absolute risk for cardiovascular events in asymptomatic persons without multiple coronary risk factors is low, regardless of whether aspirin is taken.

Encourage patients to engage in regular physical activity. 
  • Encourage otherwise healthy persons with risk factors for CAD, with or without known CAD to incorporate at least moderate aerobic physical activity in their daily lives, such as brisk walking or other similar activity, for 30 minutes or more five to seven times per week.

Evidence
  • A 2014 guideline from the USPSTF on behavioral counseling to prevent cardiovascular disease in patients with cardiovascular risk factors recommended offering intensive behavioral counseling interventions to promote healthy eating and physical activity to overweight and obese adults with additional cardiac risk factors (27).

  • A 2013 ACC/AHA guideline on lifestyle management for the reduction of cardiovascular risk recommended aerobic moderate-intensity exercise for an average of 40 minutes three to four times per week (28).

  • In a cohort study of 1960 Norwegian men, the relative risk for cardiovascular death in physically fit men after an average of 16 years was just over one-half (P=0.015) that of physically inactive men after adjustment for all other known cardiovascular risk factors (29).

  • In the Women's Health Initiative Observational Study, physical activity consisting of moderate (walking) or vigorous exercise was associated in a dose-related fashion with reduced cardiovascular risk in 73,743 postmenopausal women without known CAD. Brisk walking or vigorous exercise for ≥2.5 h/wk was associated with a 30% reduced risk for cardiovascular events (30).

  • In a prospective questionnaire from 12,138 middle-aged men without known CAD, moderately strenuous leisure-time physical activity compared with low physical activity was associated with a seven-year reduction in fatal CHD events of 40% in the MRFIT study (31).

  • A prospective study showed that improvements in physical activity in 9777 men with cardiovascular disease resulted in a 44% (CI, 25% to 59%) reduction in all-cause mortality over 5 years (32).

Rationale
  • Physical activity and physical fitness are associated with a reduced risk for CAD and cardiovascular death.

Comments
  • Moderately strenuous exercise is a reasonable part of a multifactorial approach to reducing cardiovascular risk. It is likely to have a favorable effect on lipid profiles, hypertension, obesity, and diabetes mellitus.

  • In an RCT, exercise and dietary changes reduced the risk for developing type-2 diabetes in overweight subjects with IGT (33).

  • In a 6-year RCT in Finland, moderate exercise attenuated progression of carotid intima-media thickness, a marker of atherosclerosis, in middle-aged men not taking statins (34).

Recommend a balanced diet rich in fruits, vegetables, and fiber, and low in cholesterol, saturated fats, and refined sugars.  
  • Advise patients that the current recommendation is to limit cholesterol and saturated and trans-fats in their diets.

  • Be aware that optimal diets will naturally limit saturated fats from animal sources and refined carbohydrates, and will naturally include an abundance of whole grains, fruits, and vegetables.

Evidence
  • A 2014 USPSTF statement on behavioral counseling to prevent cardiovascular disease in patients with cardiovascular risk factors recommended offering intensive behavioral counseling interventions to promote healthy eating and physical activity to overweight and obese adults with additional cardiac risk factors (27).

  • A 2013 ACC/AHA guideline on lifestyle management for the reduction of cardiovascular risk recommended that patients who would benefit from lowering their LDL adhere to a diet low in sweets, sugar-sweetened drinks, and red meat; high in fruits, vegetables, and whole grain; and that includes low-fat dairy, poultry, fish, nuts, and nontropical vegetable oils. The guideline also recommended low levels of saturated and trans fats and aerobic moderate-intensity exercise for an average of 40 minutes three to four times per week (28).

  • A systematic review and meta-analysis of the effect of increased potassium intake on cardiovascular risk factors and disease included 22 RCTs (n= 1606) and 11 cohort studies (n=127,038). The reviewers found that oral potassium supplementation was associated with a lower risk for stroke (RR, 0.76 [CI, 0.66 to 0.89]) and, in hypertensive adults, a reduction in systolic blood pressure of 3.49 (CI, 1.82 to 5.15) mm Hg and in diastolic blood pressure of 1.96 (CI, 0.86 to 3.06) mm Hg (35).

Rationale
  • Hypercholesterolemia, hypertension, diabetes mellitus, and obesity increase the risk for CAD, but the associated risk can be reduced by dietary modification.

Comments
  • Diet is a reasonable part of a multifactorial approach to reducing cardiovascular risk. It is likely to have a favorable effect on lipid profiles, hypertension, obesity, and diabetes mellitus.

  • In the Oslo Study Group trial of multiple risk-factor intervention, advice on dietary change and smoking cessation was associated with a reduction in the incidence of MI and sudden death (7); however, in the similar MRFIT trial, no reduction in CHD mortality was noted in the intervention group (6).

  • In the randomized, controlled Minnesota Coronary Survey, a low-fat diet that resulted in an approximately 15% reduction in serum cholesterol level was not associated with a significant change in the incidence of cardiovascular events, cardiovascular deaths, or total mortality (36).

Identify asymptomatic persons at high risk for ASCVD events. 
  • Estimate short- and long-term ASCVD risk in individuals age 20 to 79 years using the AHA/ACC Pooled Cohort Equations CV Risk Calculator.

  • Reevaluate each individual's ASCVD risk at 5-year intervals from the first clinical encounter or when new factors that increase risk are recognized.

  • Recognize additional risk markers for ASCVD that can influence the decision to begin intensive risk factor modification. These include

    • Genetic hyperlipidemias predisposing to ASCVD

    • Family history of premature CVD (first-degree male relative 55 years or younger or first-degree female relative 65 years or younger).

    • Measured ankle brachial index ≤0.9

    • Coronary artery calcium score when greater than ≥300 Agatston units or 75% or higher predicted for age, sex, and ethnicity

    • High sensitivity C-reactive protein ≥2 mg/L

Evidence
  • The 2013 ACC/AHA guideline on the assessment of cardiovascular risk stated that it is reasonable to assess cardiovascular risk factors every 4 to 6 years in adults age 20 to 79 years who do not have known cardiovascular disease. When individuals do not fall into predetermined high-risk categories, the use of additional risk factors based on expert opinion may influence the decision to begin primary prevention measures (9).

  • A 2014 analysis compared predicted ASCVD events by the Pooled Cohort Equations against the observed ASCVD events in the Reasons for Geographic and Racial Differences in Stroke study. The observed and predicted 5-year risks were similar, suggesting that the equations are accurate for risk prediction in the contemporary U.S. population (37).

Rationale
  • Risk factors for ASCVD frequently go unrecognized until the first clinical event. Active screening and risk factor modification results in a decrease in cardiovascular disability and death.

Comments
  • Multiple risk factor interventions for primary and secondary prevention have been studied in RCTs. They are effective in reducing cardiovascular death and disability, especially in high-risk individuals and those with diabetes mellitus (38; 39).

  • In individuals younger than 20 or older than 79 years, the utility of the Pooled Cohort Equations or the Framingham risk score remains unproven.

  • A smartphone app for ASCVD risk calculation based on the Pooled Cohort Equations is available for clinical use and provides guidance on lipid-lowering therapy based on the 2013 ACC/AHA cholesterol guidelines (40).

Do not screen asymptomatic persons for CAD except under special circumstances. 
  • Do not perform a resting ECG for screening in asymptomatic low-risk individuals.

  • Consider screening with exercise ECG stress testing in the following subgroups of asymptomatic individuals at any age:

    • Patients with multiple risk factors (hypertension, hyperlipidemia, diabetes, smoking, and cardiac event in first-degree relative before the age of 60)

    • Patients with high ASCVD risk (Framingham risk greater than 10%)

    • Sedentary patients about to undertake an intensive exercise program

  • Consider screening with exercise ECG stress testing in asymptomatic men older than 40 years and women older than 50 years when they are

    • Sedentary and about to undertake a program of vigorous exercise

    • Engaged in occupations where impairment might affect public safety (e.g., airline pilots, air traffic controllers, firefighters, and policemen)

  • Consider other modalities of stress testing in asymptomatic individuals when the baseline ECG is significantly abnormal or if the patient cannot exercise.

  • Consider screening for CAD with exercise or pharmacologic stress testing before noncardiac surgical procedures in individuals at elevated risk for ASCVD and poor (<4 METs) or unknown functional capacity, if the results of testing will change management.

  • See module Preoperative Cardiac Risk Assessment and Management.

  • See module Screening for Coronary Artery Disease.

Evidence
  • A 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery recommended consideration of stress testing in individuals at elevated risk for ASCVD and poor or unknown functional capacity when the results will change management. Further, it may be reasonable to forgo exercise testing in individuals with exercise tolerances above 4 METs (41).

  • A 2012 USPSTF statement and supporting systematic review on screening for CHD with ECG recommended against performing a routine ECG in low-risk asymptomatic adults (42; 43)

  • A 2010 ACC/AHA guideline on assessment of cardiovascular risk in asymptomatic adults did not recommend screening low-risk asymptomatic individuals with stress testing (44).

  • A 2004 systematic review of the literature published between 1966 and 2003 identified 13 studies examining the utility of exercise tolerance testing to diagnose asymptomatic coronary artery obstruction. This review concluded that previously unrecognized, clinically important coronary artery obstruction is found in 0.9% to 1.2% of screened persons with at least one risk factor and in 0.06% to 1.6% of screened persons with no risk factors (45).

  • A screening exam of 18,403 men found that abnormalities of the resting ECG are uncommon in asymptomatic middle-aged men (1% to 4%) and are not specific for CAD (46).

Rationale
  • Persons whose occupations involve public safety or are responsible for the lives of others during work are held to a higher standard of general health than the average individual.

  • Persons who engage in occupations that involve bursts of high-intensity physical activity, such as police officers or firefighters, may be at increased risk for cardiovascular events.

Comments
  • Policies regarding screening for CAD in certain occupations are frequently codified by local and national regulatory agencies.

Consider a broad differential diagnosis in patients with chest pain. 
  • Consider potentially life-threatening causes of chest pain, such as myocardial ischemia, pericardial tamponade, aortic dissection, pulmonary embolism, and pneumothorax.

    • Measure blood pressure in both arms.

    • Assess neck veins.

    • Assess respiratory status.

    • Perform pulmonary auscultation.

    • Evaluate cardiac risk factors.

    • Obtain a resting ECG and a chest X-ray.

  • Evaluate patients with suspected angina for the presence of comorbid conditions that may exacerbate angina in the presence of CAD that would otherwise not cause symptoms (functional or secondary angina).

    • Assess for tachyarrhythmia.

    • Auscultate for the presence of murmurs consistent with aortic stenosis or subaortic hypertrophic cardiomyopathy.

    • Measure hemoglobin to evaluate for anemia.

    • Consider testing for hyperthyroidism.

  • See table Differential Diagnosis of Chest Pain.

Evidence
  • The 2010 AHA scientific statement on testing of low-risk patients presenting to the emergency department with chest pain provided a systematic approach to the initial evaluation of chest pain (47).

Rationale
  • Although chest pain may have a benign cause, it is appropriate to initially exclude a life-threatening cause before diagnostic testing for CHD.

  • Functional angina is best treated by correcting the underlying condition.

  • A systematic approach to suspected nonischemic chest pain includes evaluation of the integument, nervous system, musculoskeletal system, GI system, pulmonary system, and the great vessels.

Obtain a history and examine patients for features of cardiovascular disease and comorbid diseases that may precipitate angina.  
  • Inquire about the presence of cardiovascular risk factors.

  • Inquire about potential sympathomimetic toxicity (e.g., cocaine, amphetamines, high doses of caffeine).

  • Measure vital signs.

  • Auscultate for the presence of murmurs of hypertrophic cardiomyopathy or aortic stenosis.

  • Obtain a complete blood count and basic metabolic profile.

  • Consider measuring the TSH level in persons with symptoms suggesting hyperthyroidism.

  • See table Differential Diagnosis of Chest Pain.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the diagnosis of stable ischemic heart disease recommends using the history and physical exam to assess the likelihood of ischemic heart disease before further diagnostic testing (48).

Rationale
  • Findings on physical exam suggesting peripheral arterial or cerebrovascular disease increase the likelihood of CAD.

  • Conditions that increase myocardial oxygen demand (uncontrolled hypertension, hyperthermia in the setting of hypovolemia, tachyarrhythmias, left ventricular outlet obstruction, hyperthyroidism, sympathomimetic toxicity), diminish tissue oxygenation (anemia and hypoxemia), or cause hyperviscosity (polycythemias or hypergammaglobulinemia) may precipitate angina in the setting of nonobstructive CAD.

  • The treatment of angina is best directed at the underlying cause in this setting.

Obtain a resting ECG in patients with angina.  
Evidence
  • A 2012 ACC/AHA/ACP guideline on the diagnosis of stable ischemic heart disease recommended a resting ECG in patients with chest pain (48).

  • According to a 1999 ACC/AHA/ACP guideline on management of chronic stable angina, approximately 50% of patients with angina will have an abnormal ECG finding during an episode of chest pain, and chest X-ray results are frequently normal; this finding is highly suggestive of CAD and suggests ischemia at low workloads, portending high-risk coronary anatomy, Furthermore, evidence of previous Q-wave MI on the resting ECG makes CAD very probable (49).

Rationale
  • A resting ECG may show signs of ischemia, abnormalities of conduction, abnormalities of rhythm, or left ventricular hypertrophy.

  • An ECG obtained during chest pain is most useful.

  • Chest X-ray results may show signs of HF (e.g., pulmonary edema, vascular redistribution, pleural effusions, or cardiomegaly) or arterial calcification, or may suggest causes of chest pain other than angina.

Comments
  • Many abnormalities of depolarization, repolarization, rhythm, or conduction are more common in patients with CAD but are nonspecific (49; 50).

  • A cohort study involving over 11,000 adults showed that calcification of the aorta on chest X-ray increases the probability of CAD and is associated with an increased RR for subsequent coronary events (51).

Obtain a transthoracic echocardiogram in patients with suspected significant valvular disease, signs or symptoms of HF, a history of MI, or a history of HF.  
  • Obtain standard echocardiography in patients with a systolic murmur suggesting aortic stenosis or hypertrophic cardiomyopathy.

  • Obtain a transthoracic echocardiogram (or radionuclide imaging) to assess LV function in several subsets of patients:

    • Patients with a documented history of MI

    • Patients with pathologic Q-waves on resting ECG

    • Patients with signs or symptoms suggesting HF

  • Do not routinely obtain an echocardiogram in patients with suspected angina who have a normal ECG, no history of MI, and no signs or symptoms of HF.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the diagnosis of stable ischemic heart disease recommended Doppler echocardiography in patients with signs or symptoms of HF, pathologic Q-waves on ECG, ventricular arrhythmias, or heart murmurs (48).

  • According to a 1999 ACC/AHA/ACP guideline on management of chronic stable angina, echocardiography allows accurate diagnosis in patients with significant aortic stenosis or hypertrophic cardiomyopathy (49).

  • An RCT involving 2649 patients (virtually all men) with stable CHD compared CABG with medical treatment. After 10 years, reduced LV function was associated with a worse prognosis in patients with stable angina (52).

  • In long-term follow-up from the CASS registry of 20,088 patients who underwent CABG, 72% of deaths occurred in the 38% of the population with LV dysfunction or severe CAD. A resting ejection fraction of less than 35% was associated with an annual mortality rate of greater than 3% (53).

Rationale
  • Echocardiography is useful in identifying patients with functional angina related to valvular lesions and ventricular hypertrophy, and in identifying patients with reduced LV function.

  • LV function is one of the major determinants of survival among patients with CAD.

Comments
  • In three RCTs, patients with three-vessel disease and LV dysfunction derived a clear survival benefit after CABG (54; 55; 56).

Estimate the pretest probability of CAD based on age, gender, and symptoms, or lack thereof, in all individuals before selecting a screening or diagnostic test. 
  • Ask all patients about the occurrence of anginal symptoms, and ascertain the location, nature, duration, radiation, and aggravating and relieving factors for chest pain, if any.

  • Classify the type of pain into one of three groups: typical angina, atypical angina, or noncardiac chest pain.

  • Consider that progressive angina or unstable anginal patterns are associated with an increased risk for major coronary events.

  • Calculate the pretest probability of CAD based on the patient's age, gender, and symptoms.

  • Stratify patients into categories based on the pretest probability of CAD:

    • High: greater than 90%

    • Moderate: 10% to 90%

    • Low: less than 10%

  • Refine this probability using the presence or absence of additional risk factors, such as family history of CAD in first-degree relatives, hypertension, hyperlipidemia, diabetes mellitus, and tobacco use.

  • See table Clinical Classification of Chest Pain.

  • See table Diagnostic Accuracy of Elements of the History and Physical Examination for Coronary Disease.

  • See module Screening for Coronary Artery Disease.

Evidence
  • A 2010 ACC/AHA guideline on the assessment of cardiovascular risk in asymptomatic adults did not recommend screening low-risk asymptomatic individuals with stress testing (44).

  • A 2012 ACC/AHA/ACP guideline on the diagnosis of stable ischemic heart disease recommended using the history and physical exam to assess the likelihood of ischemic heart disease before further diagnostic testing (48).

  • A 1979 literature review of several studies done in the 1960s and 1970s calculated pretest probabilities of significant CAD based on age, gender, and type of chest pain (typical angina, atypical angina, or nonanginal chest pain) (57).

  • A prospective, observational, multicenter study assessed prevalence of coronary artery stenosis via angiography in 8159 of 20,391 patients who presented with non-MI chest pain. CAD was identified in patients based on stratification: definite angina (93% of men, 72% of women), probable angina (66% of men, 36% of women), and nonspecific chest pain (14% of men, 6% of women) (all P<0.001) (58).

Rationale
  • Based on Bayesian conditional probabilities, the pretest probability for CAD in an individual determines the usefulness of a particular screening modality. It may be appropriate to perform no testing in the setting of low pretest probability or to advance to noninvasive stress testing or invasive angiography in the setting of high pretest probability.

Comments
  • A 1997 ACC/AHA guideline for exercise testing provided a table to estimate the pretest probability of CAD (59).

  • An observational prospective study included 1030 consecutive patients referred to a single center for noninvasive testing, 168 of whom ultimately underwent angiography. History, physical exam, ECG, and chest radiograph were predictors of CAD and 3-year survival rates. The study highlighted the importance of considering additional cardiac risk factors in modifying the pretest probabilities of significant CAD based on type of pain, age, and gender alone (60).

Select diagnostic tests based on the pretest probability of CAD; then refine the selection of diagnostic tests based on test contraindications, the patient's ability to exercise, and the patient's informed preferences.  
Evidence
  • A 2012 ACC/AHA/ACP guideline on the diagnosis of stable ischemic heart disease recommended using the history and physical exam to assess the likelihood of ischemic heart disease before further diagnostic testing (48).

  • The 27th Bethesda Conference reported that the probability of death from CHD at 1 year may be estimated from several readily obtainable clinical variables, including age, type of angina (nonanginal, atypical, stable typical angina, progressive angina, and unstable angina), and comorbidities (peripheral or cerebrovascular disease, diabetes, previous MI, hypertension, and mitral regurgitation). The conference also reported that risk estimates may be refined with the results of functional studies (treadmill test, stress myocardial perfusion imaging, or stress echocardiography) or coronary angiography (61).

  • A prospective cohort study of 2200 consecutive patients found that those with low-risk exercise treadmill scores generally need no further risk stratification. Fewer than 5% of patients with a low-risk exercise treadmill score are identified as having high-risk CAD after stress imaging (62).

  • A prospective cohort study of 1159 consecutive patients who underwent SPECT and were followed up for a mean of 27.5 months showed that among those with an intermediate Duke treadmill score (≥-10 and <+5), myocardial perfusion imaging helped stratify patients into low-risk and high-risk groups. For example, a normal or mild perfusion defect on scintigraphy conferred a 0.7% to 0.8% risk for cardiac death and a 1.1% to 4.4% risk for nonfatal MI over 2 years of follow-up. Patients with moderate or severe perfusion defects on scintigraphy had a 10.5% risk for cardiac death and a 6.3% risk for nonfatal MI over 2 years of follow-up (63).

  • According to the 10-year results from multiple RCTs of CABG (n=2649), subsets of patients with CAD and high short-term risk for mortality (3% or greater per year) had improved survival after CABG. Patients with LV dysfunction (LVEF 40% or less) and three-vessel CAD had improved survival after CABG (52).

Rationale
  • Findings at physical exam suggesting peripheral arterial or cerebrovascular disease increase the likelihood of CAD.

  • Conditions that increase myocardial oxygen demand (uncontrolled hypertension, hyperthermia in the setting of hypovolemia, tachyarrhythmias, LV outlet obstruction, hyperthyroidism, sympathomimetic toxicity), diminish tissue oxygenation (anemia and hypoxemia), or cause hyperviscosity (polycythemias or hypergammaglobulinemia) may precipitate angina in the setting of nonobstructive CAD.

  • The treatment of angina is best directed at the underlying cause in this setting.

Stratify patients with intermediate and high post-test probabilities of CAD according to their risk for future major coronary events.  
Evidence
  • The 27th Bethesda Conference reported that the probability of death from CHD at 1 year may be estimated from several readily obtainable clinical variables, including age, type of angina (nonanginal, atypical, stable typical angina, progressive angina, and unstable angina), and comorbidities (peripheral or cerebrovascular disease, diabetes, previous MI, hypertension, and mitral regurgitation). Risk estimates may be refined with the results of functional studies (treadmill test, stress myocardial perfusion imaging, or stress echocardiography) or coronary angiography (61).

  • A prospective observational study included 2200 consecutive patients, with a mean follow-up of 566 days after SPECT. Multiple logistic regression analysis found that referral to catheterization was almost wholly determined by scan information, with additional information provided by the presenting history and anginal pattern (clinical: 0.66 +/- 0.04; clinical + exercise: 0.73 +/- 0.04 [P=0.03]; nuclear scan: 0.87 +/- 0.03 [P<0.001]). Those with low-risk exercise treadmill scores generally need no further risk stratification, as fewer than 5% of patients with a low-risk exercise treadmill score are identified as having high-risk CAD after stress imaging (62).

  • A prospective observational study of 1159 consecutive patients, with a mean follow-up of 27.5 months after SPECT showed that among those with an intermediate Duke treadmill score (≥-10 and <+5), myocardial perfusion imaging helped stratify patients into low-risk and high-risk groups. For example, a normal or mild perfusion defect on scintigraphy conferred a 0.7% to 0.8% risk for cardiac death and a 1.1% to 4.4% risk for nonfatal MI over 2 years of follow-up. Patients with moderate or severe perfusion defects on scintigraphy had a 10.5% risk for cardiac death and a 6.3% risk for nonfatal MI over 2 years of follow-up (63).

  • According to the 10-year results from RCTs of CABG, subsets of 2649 patients (98.8% men) with CAD and high short-term risk for mortality (3% or greater per year) had improved survival after CABG compared with medical treatment. Initial CABG surgery reduced mortality significantly at 5 years (OR, 0.61; P<0.001), 7 years (OR, 0.68; P<0.001), and 10 years (OR, 0.83; P<0.03). Patients with LV dysfunction (LVEF 40% or less) and three-vessel CAD had improved survival after CABG (52).

Rationale
  • Patients with CAD may be divided according to short-term risk for cardiac death and nonfatal MI on the basis of clinical parameters and the results of noninvasive functional testing.

    • Patients with low-risk exercise treadmill scores (≥+5) have an estimated cardiac mortality rate of less than 1% per year and usually do not require further risk stratification.

    • Patients with high-risk exercise treadmill scores (<-10) have an estimated cardiac mortality rate of 3% or greater per year and should be referred for coronary angiography and possible revascularization.

    • Patients with intermediate exercise treadmill scores (≥-10 and <+ 5) may be stratified into low-risk (appropriate for medical management) and high-risk (consider revascularization) groups.

  • Patients with LV dysfunction (LVEF 40% or less) or features suggesting severe coronary disease (left-main or three-vessel disease) are at particularly high risk for death and should be evaluated for possible revascularization.

Comments
  • The Duke treadmill score does not accurately predict prognosis in patients older than 75 years. More than two-thirds of elderly patients are classified as intermediate risk, and risk category does not predict cardiac death or nonfatal MI. It is not clear whether other noninvasive functional studies are better in elderly patients (64).

  • Patients with a low post-test probability of CAD (less than or equal to 10% to 20%) generally have a favorable prognosis, eliminating the need for further risk stratification.

Recommend coronary angiography for patients with an uncertain diagnosis or high-risk features after noninvasive testing for CAD.  
  • Recommend coronary angiography in several subsets of patients with suspected angina:

    • Patients with a high pretest probability of left-main or three-vessel CAD

    • Patients with an uncertain diagnosis after noninvasive testing when the benefit of a more certain diagnosis outweighs the risk and cost of angiography

    • Patients who have survived sudden cardiac death

    • Patients in whom coronary spasm is strongly suspected

    • Selected patients with an occupational requirement for a definitive diagnosis (e.g., pilots, firefighters, or police)

  • Refer patients with high-risk CAD for possible revascularization, including patients with

    • High-risk treadmill scores (<-10)

    • Moderate or severe perfusion defects on scintigraphy and LV dysfunction at rest (LVEF 40% or less)

    • Stress-induced wall-motion abnormalities on stress echocardiography and LV dysfunction at rest

    • Intermediate- or high-risk treadmill score and LV dysfunction at rest

    • A history of aborted sudden cardiac death

  • See figure Coronary Angiogram.

Evidence
  • A 2014 ACC/AHA guideline update on the diagnosis and management of stable ischemic heart disease stated that it is reasonable to use coronary angiography to define the extent of disease in patients with a high likelihood of severe ischemic heart disease who are candidates for revascularization and in those who cannot undergo stress testing or who have nondiagnostic results on noninvasive testing (65).

  • A 2012 ACC/AHA/ACP guideline on the diagnosis of stable ischemic heart disease recommended coronary angiography in patients with a high likelihood of severe CAD in whom potential benefits outweigh potential harms. The guideline recommended against coronary angiography in patients with stable CAD who are not candidates for revascularization or in low-risk patients who have not undergone noninvasive testing (48).

  • A comparative analysis comparing exercise ECG, SPECT, PET, and coronary angiography based on published data and Bayesian mathematical model found that in patients with a high pretest probability of severe CAD (e.g., abnormalities on the resting ECG associated with chest pain), direct referral for coronary angiography may be more cost-effective than an initial noninvasive study followed by coronary angiography (66).

Rationale
  • Coronary angiography provides detailed information about coronary anatomy that cannot be obtained by other means.

  • Coronary angiography allows identification of subsets of patients at high risk (left-main coronary stenosis, three-vessel coronary stenosis, and coronary stenosis with depressed LVEF) who may have improved survival after revascularization.

  • The risks of angiography need to be balanced against its potential benefits.

Comments
  • Consultation with cardiovascular disease specialists is advised before coronary angiography since the procedure is associated with significant risks, including death (0.1%), MI (0.05%), stroke (0.07%), contrast reactions (0.37%), and vascular complications (0.4%) (67).

  • In an overview of 10-year results from seven randomized trials, subsets of patients with CAD whose survival was improved after CABG included those with left-main disease and three-vessel disease, particularly if LV function was diminished (68).

  • In one long-term follow-up study done among survivors of out-of-hospital sudden cardiac death, 71% had three-vessel disease and 6% had one-vessel CAD (69).

Consider consultation with a cardiologist for patients in whom initial invasive coronary angiography is indicated or for whom specialized clinical settings and level of care are required. 
  • Refer patients in whom diagnostic testing is limited by comorbidities or contraindications.

  • Refer patients with intermediate results or high-risk features on noninvasive testing.

  • Refer patients who have newly diagnosed HF, atrial fibrillation, premature ventricular contractions, or ventricular arrhythmias; who are sudden cardiac arrest survivors; and, in individuals with CAD, who have not yet started antiarrhythmic therapy.

  • Consult immediately with a cardiologist for all patients with sudden cardiac arrest

  • Consult immediately with a cardiologist for all patients with intermediate- to high-risk UA/NSTEMI and for all patients with suspected or proven STEMI.

  • Consider consultation with a cardiologist for patients with low-risk UA/NSTEMI.

Evidence
  • A 2001 ACP guideline on management of patients with chronic stable angina recommended consultation with a cardiologist for selected patients (70).

  • Specialized CPR and emergency cardiovascular care, as recommended in the 2013 ACC/AHA guideline on the management of STEMI (71), the 2012 ACC/AHA focused update of the guideline on the management of UA/NSTEMI (72), and the 2010 AHA guideline on CPR and emergency cardiovascular care (73), may require critical care settings and experience in noninvasive and invasive cardiovascular therapies under the guidance of a cardiovascular disease specialist.

Rationale
  • Patients with contraindications to noninvasive testing may require proceeding to invasive coronary angiography as the initial diagnostic test.

  • Coronary angiography is the gold standard for the detection of CAD and is performed by invasive cardiovascular disease specialists.

  • Patients with newly diagnosed HF, atrial fibrillation, premature ventricular contractions, and ventricular arrhythmias may require additional specialized testing and consideration for coronary revascularization.

Comments
  • Coronary angiography alone does not provide information about the physiologic significance of stenotic lesions and is a poor predictor of plaque stability and subsequent MI. However, the use of newer modalities, such as fractional flow reserve, intravascular ultrasound, and optical coherence tomography, provides additional information regarding the coronary vasculature, which may obviate the need for additional physiologic testing and may add diagnostic and prognostic information.

Refer patients at high risk for cardiovascular death and those with significant coronary stenoses producing persistent symptoms despite maximal medical therapy for evaluation for coronary revascularization.  
  • Refer for evaluation for revascularization

    • Patients with significant left-main stenosis, regardless of ventricular function

    • Patients with significant three-vessel stenoses, regardless of ventricular function

    • Patients with significant stenosis in at least one major coronary artery who have insufficient relief of angina symptoms despite maximal medical therapy

    • Patients with high-risk exercise treadmill scores (≤-11)

    • Patients with multiple moderate or a single large anterior perfusion defect on stress imaging

    • Patients with CAD and LV function below 35% to 40%

  • Individualize decisions to refer patients for revascularization. Consider a given patient's comorbid illnesses, competing mortality risks, and informed preferences.

  • Refer patients with secondary angina arising partly or entirely from cardiovascular conditions, such as hypertrophic cardiomyopathy and aortic stenosis.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended CABG in patients with left-main coronary disease, with three coronary arteries with 70% or greater stenosis in the proximal left anterior descending artery plus one additional artery. The guideline recommended PCI or CABG in patients with at least one major coronary artery with 70% or greater stenosis and unacceptable symptoms despite maximal medical therapy. The guideline recommended against stenting in patients who would be unable to tolerate dual antiplatelet therapy (74).

  • A 2014 meta-analysis of PCI outcomes in patients with stable obstructive CAD and MI included five trials involving 5286 patients with stable CAD and documented MI. The analysis compared PCI plus medical therapy with medical therapy alone on mortality and morbidity. After a median of 5 years, PCI plus medical therapy did not reduce incidence of death, nonfatal MI, unplanned revascularization, or angina compared with medical therapy alone (75).

  • A 2014 meta-analysis of CABG vs. PCI with respect to long-term mortality and morbidity in multivessel disease included six RCTs involving 6055 patients with multivessel CAD. After an average of 4.1 years, as compared with PCI, CABG led to a reduction in total mortality (RR, 0.73 [CI, 0.62 to 0.86]; P<0.001), MIs (RR, 0.58 [CI, -0.48 to -0.72]; P<0.001), and repeat vascularizations (RR, 0.29 [CI, 0.21 to 0.41]; P<0.001) (76).

  • The landmark COURAGE trial randomly assigned 2287 patients with symptomatic chronic stable angina to optimal medical therapy alone or in combination with PCI (94% stented) for a median of 4.6 years. Results documented no difference in death, MI, or other major cardiovascular events between the therapeutic approaches. Of note, this study included high-risk CAD patients, including those with previous myocardial infarct (38%), diabetes (34%), multivessel disease (69%), left anterior descending artery disease (68%), and class IV angina that was responsive to medical therapy. Surprisingly, health status improved in both treatment groups following angiography, although the PCI-treated patients showed a greater initial benefit. The initial incremental health-status benefits reported with PCI in the COURAGE trial had dissipated by 36 months when there was no difference between the two treatments (77).

  • A single-institution RCT comparing CABG vs. angioplasty vs. medical management for 214 patients with proximal left anterior descending disease showed no difference in survival among any of the three groups (78).

Rationale
  • Revascularization in patients with high-risk CAD or severely symptomatic CAD can improve survival and quality of life.

Comments
  • Although a number of studies have shown increased cardiovascular risk in patients with chronic stable angina with certain clinical criteria (e.g., noninvasive studies), revascularization therapy does not appear to confer additional protection from cardiovascular events except for those with left-main CAD or triple-vessel disease with LV dysfunction.

  • In two studies of outpatients with suspected CAD, the 4% of patients with high-risk exercise treadmill scores (< -10) had an average annual mortality of 5%. By comparison, the two-thirds of patients with low-risk exercise treadmill scores (> +5) had an average annual mortality of 0.25% (79; 80).

  • One study found that the average annual risk for cardiac death in patients with moderately or severely abnormal exercise myocardial perfusion study results is 2.1% to 4.2% (81).

  • Patients with suspected CAD and normal exercise myocardial perfusion study results have a very low annual risk for cardiac death and MI (less than 0.5% per year) (81).

  • Three large, multicenter RCTs found improved survival from 7 years and up to 18 years after CABG in patients with left-main disease or three-vessel CAD with reduced LV function (54; 55; 56).

Consider referral to a heart team to evaluate for mode of revascularization (CABG or PCI). 
  • Consider taking a heart-team approach for patients with left-main coronary stenosis or complex multivessel disease to decide which approach, PCI or CABG, offers less risk and better outcome.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended a heart-team approach in patients with unprotected left-main coronary stenosis and complex multivessel disease (74).

Rationale
  • A heart team involves collaborative decision making by an interventional cardiologist and cardiovascular surgeon after review of all available patient data and taking into account an individual patient's clinical condition and informed preferences. This approach offers individualized and patient-centered decision making when the approach to revascularization is not straightforward.

Comments
  • Referral to a center specializing in left-main coronary PCI and complex multivessel PCI should be considered when CABG for these indications is not advisable.

Evaluate patients with acute coronary syndromes in monitored settings for further evaluation and treatment.  
  • Admit persons with suspected acute coronary syndromes to a chest-pain observation unit, inpatient telemetry unit, or coronary intensive care unit depending on global clinical risk assessment, including level-of-care requirements secondary to comorbidities or complications, such as respiratory failure or cardiac arrest.

  • Consider admitting persons with unstable angina to a telemetry unit or coronary care unit if any of the following features are noted on presentation or develop subsequently:

    • Nocturnal angina or prolonged (>20 minutes) pain at rest

    • Pulmonary edema, new or worsening mitral regurgitation, S3 gallop

    • Angina at rest with dynamic ST changes ≥1 mm

    • Angina with hypotension

    • Angina with dynamic T-wave changes

    • New onset class III or IV angina in the past 2 weeks

    • Pathologic Q-waves or resting ST depression ≤1 mm in multiple lead groups

    • Age older than 65 years

  • See module Acute Coronary Syndromes.

Evidence
  • Specialized CPR and emergency cardiovascular care, as recommended in the 2013 ACCF/AHA guideline on the management of STEMI (71), the 2012 ACCF/AHA focused update of the guideline for the management of UA/NSTEMI (72), and the 2010 AHA guideline on CPR and emergency cardiovascular care (73), may require critical care settings and experience in noninvasive and invasive cardiovascular therapies under the guidance of a cardiovascular disease specialist.

Rationale
  • Emergent hospitalization allows monitoring for complications and acute application of cardiovascular interventions of proven benefit.

Treat anemia in patients with heart disease, using a restrictive blood transfusion strategy. 
  • Treat anemia in patients with heart disease, with specific therapy depending on the underlying cause.

  • Use a restrictive blood transfusion strategy in hospitalized patients with heart disease, considering transfusion in patients with a hemoglobin level <7 to 8 mg/dL.

Evidence
  • A 2013 ACP guideline on the treatment of anemia in patients with heart disease recommended a restrictive blood transfusion strategy in hospitalized patients with heart disease at a hemoglobin level <7 or 8 mg/dL. The guideline recommended against erythropoietin-stimulating agents (82).

  • A 2012 AABB guideline on red blood cell transfusion recommended that decisions about transfusion be influenced by both symptoms and hemoglobin level. In general, they recommended a restrictive transfusion strategy, with a goal hemoglobin level of 7 to 8 g/dL in stable hospitalized patients and 8 g/dL (in the absence of symptoms) in hospitalized patients with known cardiovascular disease. The guideline did not make recommendations for patients with acute coronary syndromes due to lack of evidence (83).

  • A 2012 systematic review compared restrictive and liberal transfusion strategies and included 19 trials involving a total of 6264 patients. Restrictive strategies lowered hospital mortality (RR, 0.77 [CI, 0.62 to 0.95]) but not 30-day mortality (RR, 0.85 [CI, 0.70 to 1.03]); the groups had similar rates of adverse events, including cardiac events, stroke, pneumonia, and thromboembolism. There was no difference in hospital or intensive care length of stay. Included studies did not involve patients with acute coronary syndromes (84).

  • A 1999 multicenter RCT randomly assigned over 800 patients in intensive care with hemoglobin levels of <9 g/dL within 72 hours of admission to a restrictive strategy (transfusion if hemoglobin level dropped below 7 g/dL) or a liberal strategy (transfusion if hemoglobin level dropped below 10 g/dL). Patients randomly assigned to the restrictive strategy had lower in-hospital mortality (NNT, 17; P=0.05) but no reduction in 30-day mortality. However, patients who were younger and less ill did have significantly lower 30-day mortality with the restrictive strategy (85).

Rationale
  • Severe anemia can worsen ischemia in patients with CHD.

Consider the addition of mineralocorticoid receptor antagonists and/or digoxin to medical therapy in subsets of CHD patients with HF.  
  • Initiate therapy with spironolactone or eplerenone in patients with CHD and reduced LVEF (less than 35%), when no contraindications exist.

  • Consider therapy with spironolactone in patients with CHD and higher LVEF (greater than 35%) who have symptoms of HF, when no contraindications exist.

  • Consider therapy with digoxin for patients with CHD and symptomatic HF.

  • See module Heart Failure.

Evidence
  • Three studies documented improved mortality and morbidity and/or improved symptomatology with digitalis or aldosterone blockage (spironolactone or eplerenone) in patients with worsening HF, including those with ischemic cardiomyopathy (86; 87; 88).

Comments
  • Mineralocorticoid receptor antagonists include spironolactone and eplerenone; given the higher cost of eplerenone, reserve this for patients with unacceptable steroidal side effects from spironolactone.

Choose β-blockers as the first-line antianginal therapy in most patients with angina.  
  • Treat patients with β-blockers to reduce angina severity and frequency.

  • Adjust the β-blocker dose to achieve a resting heart rate of approximately 55 to 60 beats/min and approximately 75% of the heart rate that produces angina with exertion.

  • Use β-blockers in combination with calcium-channel blockers (particularly long-acting dihydropyridines) or long-acting nitrates in the treatment of angina refractory to a single agent.

  • See table Drug Treatment for Angina.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended β-blocker therapy as the initial treatment for symptoms of stable angina and for patients who have had acute coronary syndrome (74).

  • An early systematic review of 64 randomized trials found that treatment with β-blockers after MI resulted in a 25% reduction in the risk for death (89).

  • A meta-analysis of β-blockers and progression of coronary atherosclerosis included four studies involving 1515 patients. The analysis showed that use of β-blockers slows progression of coronary atherosclerosis (90).

Rationale
  • β-blockers reduce myocardial oxygen demand by reducing heart rate and myocardial contractility, and they improve survival in patients after MI.

Comments
  • A 1999 ACC/AHA/ACP guideline on management of patients with chronic stable angina recommended titrating β-blockers to a resting heart rate of 55 to 60 beats/min and approximately 75% of the heart rate that typically produces angina with exertion (49).

  • β-blockers are contraindicated in patients with severe bradycardia, sick sinus syndrome, high-degree AV block, and decompensated HF.

  • Asthma, bronchospasm, depression, and peripheral vascular disease are relative contraindications.

  • β-blockers are generally tolerated in persons with diabetes, even persons with type-1 diabetes mellitus; however, β-blocker therapy may mask warning symptoms of hypoglycemia in patients on insulin therapy.

  • There is no consistent difference in the incidence of death and nonfatal MI between β-blockers and calcium-channel blockers in the treatment of patients with chronic stable angina (49).

Consider calcium-channel blockers as the second-line treatment in patients with angina. 
  • Treat patients who have chronic stable angina with calcium-channel blockers if they are unable to tolerate β-blockers or if symptoms are inadequately controlled with β-blockers.

  • Do not use short-acting calcium-channel blockers in the treatment of patients with angina pectoris.

  • Consider decompensated HF as a contraindication to the use of calcium-channel blockers.

  • Consider bradycardia, sinus node dysfunction, and AV nodal block as contraindications to non-dihydropyridine calcium-channel blockers.

  • See table Drug Treatment for Angina.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended calcium-channel blockers or long-acting nitrites for symptom relief in patients who cannot tolerate β-blockers or in patients for whom β-blockers do not provide adequate relief (74).

Rationale
  • Calcium-channel blockers cause vasodilation, increase coronary blood flow, and reduce myocardial contractility.

  • Non-dihydropyridine agents, such as verapamil and diltiazem, have a greater effect on myocardial contractility and conduction; dihydropyridine agents, such as nifedipine, amlodipine, felodipine, and isradipine, exert relatively more effect on vasodilation. However, short-acting and sublingual preparations of these agents can cause reflex tachycardia and are associated with an increased risk for cardiovascular events.

Comments
  • The combination of non-dihydropyridine calcium-channel antagonists (verapamil and diltiazem) with β-blockers is relatively contraindicated considering their additive effect in reducing myocardial contractility and cardiac conduction.

  • There is no consistent difference in the incidence of death and nonfatal MI between β-blockers and calcium-channel blockers in the treatment of patients with chronic stable angina (49).

Consider treatment with long-acting nitrates, alone or in combination with β-blockers or calcium-channel antagonists, in patients with uncontrolled anginal symptoms. 
  • Treat patients with long-acting nitrates as monotherapy or in combination with β-blockers or calcium-channel antagonists, or both, in patients not tolerant of other agents.

  • Note that treatment of patients with long-acting nitrates alone may result in reflex tachycardia.

  • Do not administer nitrates and oral phosphodiesterase inhibitors, such as sildenafil, tadalafil, and vardenafil, together because of the risk for life-threatening hypotension.

  • Provide an 8- to 12-hour nitrate-free period daily to prevent tachyphylaxis.

  • See table Drug Treatment for Angina.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended calcium-channel blockers or long-acting nitrites for symptom relief in patients who cannot tolerate β-blockers or in patients for whom β-blockers do not provide adequate relief (74).

Rationale
  • Nitrates alleviate anginal symptoms by dilation of epicardial coronary vessels and increasing capacitance of the venous system, resulting in diminished cardiac preload and myocardial oxygen demand.

Comments
  • Nitrates are relatively contraindicated in the setting of left ventricular outflow obstruction, e.g., hypertrophic obstructive cardiomyopathy or aortic stenosis.

Consider ranolazine or enhanced external counterpulsation in patients with refractory angina. 
  • Consider therapy with ranolazine in patients who are not optimally controlled or unable to tolerate conventional triple therapy with nitrates, β-blockers, and calcium-channel blockers.

  • Refer patients with refractory angina to a cardiovascular disease specialist for enhanced external counterpulsation or transmyocardial laser revascularization.

  • See table Drug Treatment for Angina.

Evidence
  • A 2014 ACC/AHA guideline update on the diagnosis and management of stable ischemic heart disease recommended against chelation therapy in patients with angina and stated that enhanced external counterpulsation can be considered for treatment of refractory symptoms (65).

  • A 2014 systematic review of the usefulness of ranolazine for the treatment of refractory chronic stable angina pectoris included seven RCTs involving 3,317 patients with refractory chronic stable angina due to CAD. The reviewers found improved exercise stress test parametrics with ranolazine compared with placebo, and a decrease in angina and use of nitroglycerin compared with placebo (91).

  • A 2012 meta-analysis of long-term outcomes after transmyocardial revascularization included 15,386 patients who underwent transmyocardial revascularization with or without CABG surgery. The analysis found no significant differences in long-term mortality or morbidity as compared with either procedure alone, or CABG with holmium YAG laser (92).

  • In two randomized, placebo-controlled trials, ranolazine was shown to reduce angina frequency when combined with background atenolol, diltiazem, or amlodipine therapy (93; 94).

Rationale
  • Clinical studies have shown efficacy for additional therapies in the treatment of angina.

Comments
  • Do not use chelation therapy in patients with angina.

  • Ivabradine and nicorandil are two additional antianginal agents not currently available in the United States that have been proven effective for the treatment of chronic stable angina (95; 96; 97).

Refer patients at high risk for death due to CAD or with persistent symptoms despite maximal medical therapy for evaluation for revascularization.  
  • Refer for evaluation for revascularization

    • Patients with significant left-main stenoses, regardless of ventricular function

    • Severely symptomatic patients with significant three-vessel disease, regardless of ventricular function (patients with reduced LV function benefit more than patients with normal LV function)

    • Patients with known significant stenosis in at least one major coronary artery who have insufficient relief of angina symptoms despite maximal medical therapy

    • Patients with high-risk treadmill scores (<-10)

    • Patients with intermediate treadmill scores and LV dysfunction at rest

    • Patients with moderate or severe perfusion defects on scintigraphy and LV dysfunction at rest (LVEF 40% or less)

    • Patients with stress-induced wall-motion abnormalities on stress echocardiography and LV dysfunction at rest

    • Patients with a history of aborted sudden cardiac death

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended consideration of CABG in patients with left-main coronary disease, with three coronary arteries with 70% or greater stenosis in the proximal left anterior descending artery plus one additional artery. PCI may be an acceptable alternative in these settings when CABG is associated with markedly elevated surgical risk. A heart-team approach was recommended in such cases. The guideline recommended PCI or CABG in patients with at least one major coronary artery with 70% or greater stenosis and unacceptable symptoms despite maximal medical therapy. The guideline also recommended against stenting in patients who would be unable to tolerate dual antiplatelet therapy (74).

  • A randomized trial compared PCI with CABG in 1800 patients with three-vessel coronary disease or left-main disease. After 5 years of follow-up, patients in the surgery group had a lower rate of the combined primary endpoint of long-term major adverse coronary and cerebrovascular events (PCI NNH, 10) (98; 99).

  • Three large, multicenter, randomized trials showed improved survival in patients with left-main disease or three-vessel CAD with reduced LV function (54; 55; 56).

  • The COURAGE trial randomly assigned patients with symptomatic chronic stable angina to optimal medical therapy alone or in combination with PCI (94% stented) and found no difference in death, MI, or other major cardiovascular events between the therapeutic approaches. Of note, this study included high-risk CAD patients, including those with previous myocardial infarct (38%), diabetes (34%), multivessel disease (69%), left anterior descending artery disease (68%), and class IV angina that was responsive to medical therapy. The COURAGE study also evaluated health status and found improvements in both treatment groups following angiography, although patients treated with PCI showed a greater initial benefit (77).

  • A randomized trial of CABG vs. angioplasty vs. medical management for patients with proximal left anterior descending disease showed no difference in survival among any of the three groups (78).

  • In two studies of outpatients with suspected CAD, the 4% of patients with high-risk exercise treadmill scores (< -10) had an average annual mortality of 5%. By comparison, the two-thirds of patients with low-risk exercise treadmill scores (> +5) had an average annual mortality of 0.25% (79; 80).

  • One study found that the average annual risk for cardiac death in patients with moderately or severely abnormal exercise myocardial perfusion study results was 2.1% to 4.2%. Patients with suspected CAD and normal exercise myocardial perfusion study results had a very low annual risk for cardiac death and MI (81).

Rationale
  • Patients at high risk for subsequent death from CAD may benefit from revascularization.

Comments
  • Although a number of studies have shown increased cardiovascular risk in patients with chronic stable angina with certain clinical criteria (e.g., noninvasive studies), revascularization therapy does not appear to confer additional protection from cardiovascular events except for those with left-main CAD or triple-vessel disease with LV dysfunction.

  • The significance of stenosis may be determined by angiographic evaluation (greater than 50% left main, greater than 70% other vessel), measured by fractional flow reserve (<0.80) (100), or inferred by intravascular ultrasound luminal area measures.

  • Individualize decisions to refer patients for evaluation for revascularization in light of a given patient's comorbid illnesses, competing mortality risks, and informed preferences.

Refer patients with CAD and reduced LVEF to a heart rhythm specialist for consideration of ICD or CRT.  
  • Refer for evaluation ICD patients with CAD and LVEF less than 35% who are at least 40 days post-MI (indicated in NYHA class II and III, or for NYHA class I with LVEF less than 30%).

  • Refer for evaluation ICD patients who have sustained VT or have VF.

  • Refer for evaluation ICD patients with previous MI and nonsustained VT with LVEF less than 40%, who develop inducible sustained VT or VF during electrophysiologic study.

  • Refer for evaluation CRT patients with CAD and LVEF less than 35% who are at least 40 days post-MI. The decision to implant a CRT device will depend on further specialist evaluation of functional status, life expectancy, QRS duration, and pattern of QRS prolongation.

  • See module Implantable Cardioverter Defibrillator.

Evidence
  • A 2008 ACC/AHA/HRS guideline on device-based therapy of cardiac rhythm abnormalities recommended consideration of ICD implantation in specific subsets of patients (101).

  • The 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guideline on device-based therapy of cardiac rhythm abnormalities recommended evaluation for CRT implantation in specific subsets of patients with CAD and LVEF less than 35%, after further evaluation by a heart rhythm specialist (102).

  • A 2011 meta-analysis of CRT in patients with minimal HF identified five clinical trials including 4,317 patients with NYHA class I/II HF for inclusion. The analysis showed frequency of all-cause mortality to be 8% for CRT vs. 11.5% for ICD (RR, 0.81 [CI, 0.65 to 0.99]; P=0.04). Patients assigned to CRT had a significantly greater improvement in LVEF than patients assigned to ICD (103).

  • A 2003 meta-analysis of CRT and death from progressive HF included four RCTs with 1634 patients. The analysis found that, compared with controls, CRT reduced HR-related death by 51% (OR, 0.49 [CI, 0.25 to 0.93]) (104).

  • A 2003 meta-analysis of the effectiveness of ICDs for preventing arrhythmic events and death included nine RCTs including more than 5,000 patients. For primary and secondary prevention of sudden cardiac death, the analysis showed an RR of 0.34 and 0.50, respectively (both P<0.001), all due to reduction in arrhythmic death (P<0.00001) (105).

Rationale
  • Patients with CAD and reduced LVEF are at elevated risk for sudden cardiac death. The presence of an ICD can provide prompt defibrillation of VT or VF and has been proven to increase survival in these patients.

  • Patients with CAD and reduced LVEF with specific markers of cardiac dyssynchrony may have a decrease in HF symptoms, improved quality of life, and prolonged survival after implantation of CRT.

Comments
  • Implantation of subcutaneous ICD systems may be considered in select groups of patients who do not require electronic atrial or ventricular pacing or who would be at high risk for device-related complications related to intravascular defibrillation leads.

Refer patients with clinical CHD and its complications for cardiopulmonary rehabilitation.  
  • Refer for cardiopulmonary rehabilitation all patients with CHD and

    • Acute coronary syndrome or MI

    • PCI

    • CABG

    • Chronic stable angina

    • Systolic HF with symptoms

  • Know that cardiopulmonary rehabilitation typically provides the following services to patients:

    • Physician-prescribed exercise

    • Cardiac risk-factor modification, including education, counseling, and behavioral intervention directed at physical activity, nutrition, lipid management, blood pressure management, smoking cessation, weight management, diabetes management, and psychosocial management

    • Psychosocial assessment: evaluation of the individual's mental and emotional functioning as it relates to the individual's rehabilitation or cardiac condition

    • Outcomes assessment: evaluation of the patient's progress as it relates to the individual's rehabilitation goals and program

Evidence
  • A 2005 AHA scientific statement on cardiac rehabilitation and secondary prevention of CHD defined cardiac rehabilitation as coordinated, multifaceted interventions designed to optimize a cardiac patient's physical, psychological, and social functioning, in addition to stabilizing, slowing, or even reversing the progression of the underlying atherosclerotic processes, thereby reducing morbidity and mortality. The statement cited that cardiac rehabilitation programs remain underused in the United States, with an estimated participation rate of only 10% to 20% of the more than 2 million eligible patients per year who experience an acute MI or undergo coronary revascularization. Contributing to the vast underuse of these services are a low patient referral rate, particularly of women, older adults, and ethnic minority patients; poor patient motivation; inadequate third-party reimbursements for services; and geographic limitations to accessibility of program sites (106).

  • A 2004 meta-analysis of 48 trials randomly assigned 8940 patients to cardiac rehabilitation or usual care. Cardiac rehabilitation was associated with reduced all-cause mortality (OR, 0.80 [CI, 0.68 to 0.93]) and cardiac mortality (OR, 0.74 [CI, 0.61 to 0.96]) along with significant improvement in several cardiac risk factors, but with no decrease in nonfatal MI and revascularization or improvements in HDL or LDL cholesterol levels (107).

  • The 2009 HF-ACTION multicenter RCT of 2331 patients with HF and reduced ejection fraction found nonsignificant reductions for mortality, cardiovascular mortality, and hospitalizations in the group prescribed aerobic exercise training (108).

Rationale
  • Patients with CAD and its complications benefit mentally and physically from undergoing rehabilitation.

  • Cardiac rehabilitation centers are multimodality secondary-prevention institutes where multifactorial educational interventions directed at cardiac risk factors, such as smoking, obesity, hypertension, hyperlipidemia, and diabetes, are instituted and maintained.

  • Cardiac rehabilitation is effective in secondary prevention of ASCVD events.

Comments
  • Individualize decisions to refer patients for evaluation for rehabilitation in light of a given patient's comorbid illnesses, competing mortality risks, and informed preferences.

  • Additional information regarding cardiac rehabilitation can be found on the American Association of Cardiovascular and Pulmonary Rehabilitation website.

Treat patients with CAD for secondary prevention with aspirin and other antiplatelet therapy as indicated, barring contraindication. 
  • Prescribe aspirin, 75 to 162 mg daily, for all patients with angina, unless they have a history of significant bleeding events or aspirin allergy.

  • Prescribe clopidogrel as antiplatelet monotherapy in patients in whom aspirin is contraindicated.

  • Prescribe dual antiplatelet therapy with aspirin and either clopidogrel, prasugrel, or ticagrelor at appropriate doses

    • For 1 year in patients with CAD and acute coronary syndrome, barring contraindications

    • For at least 1 month after bare-metal stent implantation and 12 months after drug-eluting stent implantation

  • Prescribe no more than 81 mg of aspirin daily in patients taking ticagrelor.

  • See table Drug Treatment for Angina.

Evidence
  • A 2012 ACC/AHA focused update of the guideline for the management of UA/NSTEMI and a 2013 ACC/AHA guideline on the management of STEMI provided specific recommendations for the use of dual antiplatelet therapy after acute coronary syndrome or after PCI (72; 71).

  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended aspirin at a dose of 75 to 162 mg/d in patients with CAD who have no contraindication. The guideline also recommended use of clopidogrel when aspirin is contraindicated due to intolerance or allergy (74).

  • A 2009 Antithrombotic Trialists' Collaboration meta-analysis of aspirin for the primary and secondary prevention of vascular disease included 95,000 low-risk patients in 6 primary prevention trials and 17,000 high-risk patients in 16 secondary prevention trials. In the secondary prevention trials, comparing aspirin with placebo, there was an absolute reduction in serious vascular events (6.7% vs. 8.2% per year; P<0.0001), total strokes (2.08% vs. 2.54% per year; P=0.002), and coronary events (4.3% vs. 5.3% per year; P<0.0001) (23).

  • In the PLATO RCT, ticagrelor was compared with clopidogrel as dual antiplatelet therapy on a background of aspirin for cardiovascular death. In patients who had an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, MI, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure related bleeding. A subset analysis of the PLATO trial showed no reduction in mortality in patients in the U.S. who were on aspirin doses >81 mg daily (109).

  • In the TRITON-TIMI 38 RCT, prasugrel was compared with clopidogrel as dual antiplatelet therapy on a background of aspirin for cardiovascular mortality and morbidity. In patients with acute coronary syndromes with scheduled PCI, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk for major bleeding, including fatal bleeding. Overall mortality did not differ significantly between treatment groups (110).

  • In the CAPRIE study, clopidogrel, as compared with aspirin, showed a statistically significant, although small, reduction in the incidence of the combined endpoint of stroke, MI, or vascular death. The study population consisted of patients with a history of recent MI, stroke, or symptomatic vascular disease (111).

  • In several randomized trials, aspirin reduced the risk for death and/or MI by approximately one-third in patients with stable angina (26; 112; 113).

Rationale
  • Aspirin reduces platelet aggregation and acute coronary events.

  • Aspirin reduces the risk for MI and death in patients with angina.

  • Dual antiplatelet therapy after acute coronary syndrome reduces the risk for recurrent ASCVD events and mortality related to CAD.

  • Dual antiplatelet therapy after stent implantation significantly reduces the risk for stent thrombosis.

Comments
  • Clopidogrel is a reasonable alternative to aspirin for patients with contraindications to aspirin, except when the contraindication is because of major or minor bleeding events or increased bleeding risk.

  • Data show benefit from extension of dual antiplatelet therapy beyond the recommended duration after acute coronary syndrome or PCI. This decision should be individualized based on perceived ASCVD clinical risk, major and minor bleeding risk, patient preference, and cost factors.

Treat all patients with ASCVD, including CHD, with a moderate- to high-intensity statin.  
  • Treat patients with CAD who are younger than age 75 with high-dose atorvastatin (40 to 80 mg) or rosuvastatin (20 to 40 mg).

  • Use moderate-intensity statin therapy in patients with CAD who are older than age 75.

  • In individuals at higher risk for ASCVD who are unable to take any statin, or in those who remain at elevated risk on maximal tolerated statin intensity, consider the addition of non-statin LDL cholesterol-lowering therapy, provided that the estimated benefit outweighs the risk for adverse effects.

  • See table Therapeutic Intensity of Statin Doses.

  • See module Lipid Disorders (Dyslipidemia).

Evidence
  • A 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce the risk for cardiovascular disease recommended high-intensity statin therapy for patients younger than age 75 with known ASCVD and moderate-intensity statin therapy for patients older than age 75 (40).

  • A 2010 Cholesterol Treatment Trialists' Collaboration meta-analysis of data from 170,000 patients across 26 RCTs of statins for primary and secondary prevention evaluated outcomes of major vascular events (coronary death, nonfatal infarction, coronary revascularization, and ischemic stroke). Over a median follow-up of about 5 years, compared with placebo groups, the statin groups had a proportional reduction in major vascular events per 1.0 mmol/L LDL cholesterol reduction (RR, 0.78 [CI, 0.76 to 0.80; P<0.0001). As compared with less intensive statin therapy, the patients receiving more intensive statin therapy had an additional 15% reduction in major vascular events, in particular reductions in coronary death and nonfatal MI (P<0.0001), coronary revascularization (P<0.0001), and ischemic stroke (P=0.005) (10).

  • A 2013 individual patient meta-analysis of the effects of high-dose atorvastatin compared with low-dose atorvastatin or simvastatin in patients with coronary disease included 15,056 patients. High-dose atorvastatin decreased cardiovascular events (NNT, 66 [CI, 43 to 165]) and increased the incidence of diabetes (NNT varied from 95 [CI, 51 to 505] to 39 [CI, 22 to 113]), depending on diabetes risk factors (114; 115).

  • A 2007 systematic review and meta-analysis of intensive compared with moderate lipid lowering included six trials involving 110,271 patient-years. In patients with acute coronary syndromes, intensive statin therapy reduced mortality over 2 years (OR, 0.75 [CI, 0.61 to 0.93]). In patients with stable coronary disease, intensive statin therapy did not reduce mortality over 4.7 years (OR, 0.99 [CI, 0.89 to 1.11]) (116).

Rationale
  • Statin therapy in patients with known CAD improves survival and reduces the risk for major coronary events.

  • There is limited evidence that addition of nonstatin lipid-lowering therapy on a background of statin therapy lowers ASCVD risk or CHD-related clinical events, and in fact, there may be increased adverse events related to nonstatin drug-related side effects.

Treat patients with CAD and additional specific indications with ACE inhibitors or ARBs, barring contraindications. 
  • Treat patients with CAD and LVEF less than 40% with an ACE inhibitor or ARB.

  • Treat patients with CAD and one or more additional cardiovascular risk factors (diabetes, hypertension, dyslipidemia, microalbuminuria, or tobacco use) with an ACE inhibitor or ARB.

  • Prescribe ARBs when ACE inhibitors are contraindicated due to allergies or intolerances, if the allergy or intolerance would not be expected to recur with ARB use.

  • Do not use simultaneous ACE inhibitors and ARB therapy for any indication.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended ACE inhibitors in patients with CAD who also have hypertension, diabetes, ejection fraction 40% or less, or chronic kidney disease, unless there are contraindications. The guideline recommends ARBs for patients qualifying for ACE inhibitors who are unable to tolerate them (74).

  • A 1998 systematic review of four large trials evaluating secondary prevention in 98,496 patients who recently sustained an acute MI found improved survival with ACE inhibitor treatment in the immediate peri-infarction period. There was a 7% relative reduction in 30-day mortality in patients with acute MI treated with ACE inhibitors initiated within 36 hours of the onset of chest pain. The ARR in 30-day mortality was 4.8 deaths per 1000 patients treated (NNT, 208), and 80% of this benefit accrued during the first week after MI. The absolute benefit is greatest in persons at highest risk for short-term mortality after MI (persons with anterior MI, clinically evident CHF, tachycardia at entry, or Killip class 2 or 3) (117).

  • Several large RCTs show a mortality benefit in patients with HF and LVEF less than 35% treated with an ACE inhibitor (118; 119).

  • In the CONSENSUS trial, enalapril titrated to 40 mg/d in patients with class IV HF reduced mortality by 18% at 6 months (NNT, 5.5) (120).

  • In the SOLVD prevention trial, enalapril titrated to 20 mg/d in patients with asymptomatic LV dysfunction (LVEF less than 35%) reduced death from HF, hospitalization for HF, and the composite outcome of death or development of HF (121).

  • A prospective RCT showed that angiotensin-receptor antagonists may offer comparable benefit to ACE inhibitors in patients with HF (122).

  • In the HOPE RCT, 3577 patients with either vascular disease or diabetes and at least one additional cardiovascular risk factor who were treated with ramipril, 10 mg/d, for an average of 4.5 years had a significantly reduced risk for composite cardiovascular events (the primary outcome), total mortality, cardiovascular mortality, MI, stroke, HF, diabetic complications, revascularization procedures, and cardiac arrest (123). The RRs for each of these outcomes ranged from 0.63 to 0.84 across a range of predefined subgroups. The ARR of the composite outcome (MI, stroke, or cardiovascular death) was 3.8% (NNT, 26), and the ARR in total mortality was 2.8% (NNT, 36) patients treated for 4.5 years. The absolute benefit in patients with diabetes was slightly higher than the overall reported benefit (124).

  • Using a prospective, randomized, double-blind design, the ONTARGET study compared the efficacy of ramipril with telmisartan and the combination of the two in patients with vascular disease or high-risk diabetes. They reported that telmisartan alone or in combination with ramipril was equivalent to ramipril alone in preventing cardiovascular events, although the combined therapy was associated with more adverse effects (125).

Rationale
  • Treatment with an ACE inhibitor or ARB therapy reduces mortality in patients with HF and reduced LV function.

  • Treatment with an ACE inhibitor or ARB therapy reduces mortality, composite cardiovascular events, MI, and stroke in patients with documented vascular disease or diabetes and at least one additional cardiovascular risk factor.

Comments
  • Major side effects include hypotension (particularly in the setting of hypovolemia, diuretic use, or acute MI), hyperkalemia (particularly in patients with renal insufficiency and those taking potassium-sparing diuretics or potassium supplementation), and renal insufficiency (particularly in patients with renal artery stenosis, severe HF, or volume depletion). The therapeutic property of ACE inhibitors is thought to be a class effect.

  • ACE inhibitors and ARB therapy are also indicated in subsets of patients with acute MI. See module Acute Coronary Syndromes.

  • The 2014 evidence-based guideline from the JNC 8 panel members on the management of high blood pressure in adults recommended against the combined use of ACE inhibitors and ARB therapy in the same patient (12).

Counsel smokers to quit smoking to reduce their cardiac risk. 
  • Inquire about smoking status and exposure to secondhand smoke in all patients.

  • Quantify tobacco use, estimate secondhand smoke exposure, recommend smoking cessation, and provide psychological and pharmacologic support at each visit to all patients who want to quit smoking.

  • Use the following approach to encourage smoking cessation in the primary care setting:

    • Systematically identify all tobacco users.

    • Recommend smoking cessation at each visit to patients who smoke.

    • Identify patients who are willing to attempt to quit smoking.

    • Assist patients with the development of a cessation plan.

    • Encourage nicotine replacement and bupropion or varenicline unless contraindicated.

    • Schedule follow-up contact in person or by telephone.

  • See module Smoking Cessation.

Evidence
  • A 2012 ACC/AHA/ACP guideline for the management of stable ischemic heart disease recommended advising all smokers with CHD to stop smoking and for all patients to avoid environmental exposure to smoke (74).

  • A randomized trial of an intensive smoking cessation intervention vs. standard counseling in patients with acute coronary syndromes showed that the intensive intervention prevented all-cause mortality, with an NNT of 11 over 2 years (126).

  • According to a 1990 Surgeon General's report, patients who continue to smoke after MI have a 22% to 47% increased risk for death (127).

  • An RCT of 173 consecutive smoking patients admitted for acute MI found that patients with symptomatic CAD were particularly receptive to treatment directed at smoking cessation (128).

Rationale
  • Among patients with CAD, continued smoking is associated with an increase in cardiovascular mortality, while cessation reduces that risk.

  • The risk for MI declines rapidly in the first several months after smoking cessation.

Comments
  • There is insufficient data to make a recommendation on the use of electronic cigarettes in patients with CHD, either for personal pleasure or as smoking cessation aids. However, physiologic risk profiles from these devices suggest against their use until more data are available.

Recognize that regular aerobic exercise is an important part of a multifactorial approach to cardiac risk reduction. 
  • Encourage persons with chronic stable angina to incorporate at least moderate aerobic physical activity in their daily lives.

  • Note that moderate physical activity consists of walking briskly for 30 minutes or more, or a similar activity, five to seven times per week.

Evidence
  • A 2013 ACC/AHA guideline on lifestyle management for the reduction of cardiovascular risk recommended that all patients engage in aerobic moderate-intensity exercise for an average of 40 minutes three to four times per week (28).

  • Three randomized trials of the effects of regular aerobic exercise in patients with chronic stable CAD have shown reduction in symptoms or markers for myocardial ischemia (129; 130; 131).

Rationale
  • Regular aerobic exercise reduces cardiac risk.

Comments
  • There were fewer than 250 subjects, all men, in the three randomized studies cited.

Recognize that dietary modification is an important component of multifactorial cardiac risk reduction. 
  • Recommend a diet low in cholesterol and saturated and trans fats in patients with stable angina.

  • Emphasize that consumption of diets rich in fresh fruits and vegetables and replacement of saturated fats with monounsaturated fats is particularly desirable.

Evidence
  • A 2013 ACC/AHA guideline on lifestyle management for the reduction of cardiovascular risk recommended that patients who would benefit from lowering their LDL adhere to a diet low in sweets, sugar-sweetened drinks, and red meat; high in fruits, vegetables, and whole grains; and which includes low-fat dairy, poultry, fish, nuts, and nontropical vegetable oils. The guideline also recommended low levels of saturated and trans fats and aerobic moderate-intensity exercise for an average of 40 minutes three to four times per week (28).

  • A 2012 ACC/AHA/ACP guideline on the diagnosis of stable ischemic heart disease recommended a low-fat diet and lifestyle modification, and moderate- or high-dose statins for patients with CAD without contraindications or side effects (74).

  • A study of the so-called Mediterranean diet evaluated the effect of a diet low in saturated fats and rich in fresh fruits, vegetables, whole grains, and monounsaturated fats in patients with a history of MI. This study showed significant reductions in death and nonfatal MI, as well as major cardiovascular endpoints (132). A similar diet reduced cardiovascular events in a south Asian population at high risk for CAD (133).

Rationale
  • Diet contributes to other cardiac risk factors, including dyslipidemia, hypertension, obesity, and diabetes mellitus.

  • Diets low in fat, particularly saturated fats and cholesterol, may help reduce serum cholesterol levels and cardiovascular risk.

Develop an individualized and systematic approach to patient education. 
  • Assess the patient's baseline understanding of his or her condition.

  • Elicit the patient's desire for information.

  • Use epidemiologic and clinical evidence; quantify risk in terms that are understandable to the patient.

  • Use ancillary personnel and patient educators when appropriate.

  • Use professionally prepared resources when available.

  • Engage the patient in the development of a realistic and attainable therapeutic plan.

  • Involve family members in educational efforts.

  • Reinforce patient education frequently.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended personalized education for patients with CHD (74).

Rationale
  • Educational efforts need to be tailored to individual patients, congruent with their desire to adopt changes in medications or lifestyle, and reinforced over time in order to be effective.

Discuss with the patient modifiable cardiac risk, treatment, prognosis, and physical activity, and how to contact the medical system in the setting of progressive symptoms or an acute coronary event. 
  • Review with the patient

    • Important risk factors, emphasizing potentially modifiable risk factors

    • Potential complications (unstable angina, MI, HF, arrhythmia, and sudden death)

    • Individual prognosis

    • Benefits and potential side effects of medications

    • The proper method of administration of medications (doses, timing, precautions)

    • Any limitations on physical activity, including sexual activity

  • Instruct the patient regarding the following aspects of an acute cardiac event:

    • Warning signs and symptoms of MI (progressive symptoms vs. acute coronary syndromes)

    • Prompt use of aspirin and nitroglycerin

    • How to contact emergency medical personnel

    • Location of the nearest hospital with 24-hour emergency cardiovascular services

  • Consider advising CPR training for family members.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended education for patients with CAD, including personalized education about medication adherence, risk reduction strategies, therapeutic options, exercise, and self-monitoring. Specific recommended topics include weight management, lipid and blood pressure management, and avoidance of cigarette smoke (74).

Rationale
  • Individualized, systematic patient education is likely to improve adherence to medical therapy and patient satisfaction and may improve functional status and survival.

Schedule periodic follow-up according to the stability of clinical status and the establishment of consistent communication with patients and other physicians involved in the care of the patient. 
  • See patients with successfully treated chronic stable angina every 4 to 6 months for the first year, then every 4 to 12 months thereafter.

  • Consider longer visit intervals for patients with stable symptoms who are reliable enough to call or make an appointment when they have new or changing symptoms.

  • Realize that communication among physicians is paramount for patients comanaged by their primary care physician and cardiologist.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended periodic follow-up to assess symptoms, complications, risk factors, and adherence to therapy (74).

  • There is little evidence to support specific visit intervals (49).

Rationale
  • Follow-up visits are appropriately more frequent after the initiation and titration of medical management.

Comments
  • Changes in clinical status may result from comorbid disease, medication side effects, nonadherence with recommended drug therapy, or social factors, as well as progression of CHD.

Obtain a follow-up history, focusing on angina symptoms, medication use, and modifiable cardiac risk factors. 
  • Inquire about any changes since the last visit:

    • Change in level of physical activity

    • Increased anginal symptoms in frequency or severity

    • New exacerbating and alleviating conditions

    • Success in modifying risk factors and improved knowledge about ischemic heart disease

    • New comorbid illnesses or changes in the severity or treatment of known comorbid illnesses that have worsened the patient's angina

  • Assess the patient for adherence to therapy and adverse drug effects.

  • Review with the patient his or her action plan for an MI or other acute coronary event.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended periodic follow-up to assess symptoms, complications, risk factors, and adherence to therapy (74).

  • The efficacy and side effects of commonly used medications are reviewed in the table Drug Treatment for Angina.

Rationale
  • Changes in angina severity or frequency may indicate worsening CAD, changes in comorbid conditions, or changes in social factors (e.g., personal finance) that may affect disease severity.

  • Changes in angina symptoms may warrant changes in medications or risk stratification to evaluate whether revascularization is now appropriate.

  • Review of medical therapy is even more important in the elderly who may be particularly prone to drug side effects and polypharmacy.

  • Attention to modifiable risk factors (e.g., smoking) at each visit increases the likelihood of successful risk reduction.

Perform a careful physical exam, focusing on the cardiovascular system and directed by changes in symptoms. 
  • Conduct the physical exam according to the patient's history.

  • Measure weight, blood pressure, and heart rate at each visit.

  • Assess jugular venous pressure and waveforms, carotid pulsation magnitude and upstroke, and the presence or absence of carotid bruits.

  • Conduct a thorough pulmonary exam, focusing on the presence of crackles, wheezes, rhonchi, diminished breath sounds, and dullness to percussion.

  • Conduct a cardiac exam, and note any presence of gallops, new or changing murmurs, and location and size of the apical impulse.

  • Examine the abdomen, looking for hepatomegaly, abdominojugular reflux, and the presence of abdominal pulsations consistent with an aortic aneurysm.

  • Conduct a vascular exam, including evaluation of peripheral pulses and the presence of any bruits.

  • Evaluate for new or worsening peripheral edema.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended periodic follow-up to assess symptoms, complications, risk factors, and adherence to therapy (74).

Rationale
  • Signs of HF identify patients with CHD at high risk (average annual mortality rate greater than 3%).

  • Persons with CHD may be at risk for peripheral vascular and cerebrovascular disease.

Use selective lab evaluation to monitor reduction of modifiable risk factors. 
  • Measure serum electrolyte levels, renal function, hepatic function, hemoglobin level, and thyroid function annually and obtain these at shorter intervals as indicated by the patient's history, physical exam, or clinical course.

  • Perform routine lab testing for ASCVD risk factor-related conditions, such as glycosylated hemoglobin levels, urine microalbumin measurement, or fasting lipid panels (see Prevention).

  • See module Diabetes Mellitus, Type 1.

  • See module Diabetes Mellitus, Type 2.

  • See module Essential Hypertension.

  • See module Lipid Disorders.

Evidence
  • A 2012 ACC/AHA/ACP guideline on the management of stable ischemic heart disease recommended periodic follow-up to assess symptoms, complications, risk factors, and adherence to therapy (74).

Rationale
  • Continued monitoring for emergence of new and evolution of old ASCVD risk factors is needed over the long term.

  • While routine testing to monitor for side effects of drugs used to treat CHD and its risk factors is not recommended, specific testing should be performed when clinically suggested.

Do not perform routine, periodic resting ECGs. 
  • Do not perform routine, periodic resting ECGs in the absence of changes in medications, symptoms, or physical exam.

  • Consider an ECG when medications affecting cardiac conduction (e.g., digoxin) are initiated or changed.

  • Order an ECG for a change in the anginal pattern, symptoms of HF, symptoms or findings suggesting a dysrhythmia or conduction abnormality, and near or frank syncope.

Evidence
  • The 1999 ACC/AHA/ACP guideline on the treatment of chronic stable angina found no clear evidence that periodic resting ECGs are useful in the absence of changes in the clinical history or physical exam (49). Follow-up resting ECG is not addressed in the 2012 guidelines.

Rationale
  • An ECG is essential to evaluate new or worsening angina, HF, or dysrhythmia.

  • Many medications commonly used in the treatment of angina, dysrhythmia, or HF have the potential to affect cardiac conduction (e.g., β-blockers, calcium-channel antagonists, digoxin, or antiarrhythmics).

Obtain a repeat stress test in patients if changes in symptoms warrant risk stratification or if the outcome is likely to influence a decision to proceed with revascularization. 
  • Do not perform repeat stress testing in the absence of a change in clinical status, in low-risk patients with an estimated annual mortality rate of less than 1% for at least 3 years after the initial evaluation.

  • Order an exercise ECG test at 1 year or longer intervals (when the ECG is interpretable), or exercise or pharmacologic stress imaging (dobutamine stress echocardiography, myocardial perfusion imaging, or cardiac magnetic resonance imaging) ) at ≥2-year intervals in patients with a history of silent ischemia and/or high risk for recurrent events,

  • Perform a repeat noninvasive stress test in patients with new or worsening anginal symptoms, provided the patient is a candidate for revascularization.

Evidence
  • The 2012 ACC/AHA/ACP guideline on diagnosis of stable ischemic heart disease provided recommendations for stress testing in symptomatic patients as well as repeat interval testing in high-risk asymptomatic patients (48).

Rationale
  • Risk stratification of patients with stable angina allows patients to be grouped into low, intermediate, and high risk for death from CHD during the ensuing 3 years.

  • The intermediate-term prognosis and natural history of various patient cohorts with chronic stable angina is well documented.

  • Aside from patients who have intermediate- or high-risk unstable angina, little is known about what defines clinically important changes in anginal symptoms in patients with known CAD.

Comments
  • Choose a repeat stress test according to the outlined recommendations on the diagnosis and risk stratification of patients with angina.

Table Grahic Jump Location
 Diagnostic Accuracy of Elements of the History and Physical Examination for Coronary Disease

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ElementSensitivity (%)Specificity (%)Likelihood Ratio PositiveLikelihood Ratio NegativeNotes
Typical angina91 (male)
89 (female)
87 (male)
63 (female)
7.0 (male)
2.4 (female)
0.1 (male)
0.2 (female)
Typical angina has three components. 1) Location: substernal, jaw, neck, back, epigastrium, or arm. 2) Quality: squeezing, heavy, suffocating. 3) Exacerbated by exertion or stress and relieved with rest or nitroglycerine. Data were derived from an angiography referral population (134) and may overestimate the accuracy of the history
Pressure-like pain65591.60.6Test characteristics are for the prediction of MI among patients with normal ECG or only nonspecific ECG who presented to emergency departments with chest pain (135). The sensitivity and specificity for the diagnosis of CAD are uncertain
Radiation to the arm or jaw48681.50.8(135)
Diaphoresis32771.40.9(135)
Substernal chest pain85331.30.5Test characteristics are for the prediction of MI among patients who presented to emergency departments with chest pain, including patients with ECGs diagnostic of acute MI (136). The sensitivity and specificity for the diagnosis of CAD are uncertain
Reproduced with palpation3830.21.2(136)
Reproduced with deep inspiration4820.21.2(136)
Reproduced with change in position3860.21.1(136)
Radiation to the left arm47853.10.6Test characteristics were reported for the diagnosis of MI or coronary disease among 278 patients who presented to an emergency department with chest pain (137). The diagnosis of coronary disease in this study was questionable
Radiation to the anterior jaw49853.20.6(137)
Radiation to the right arm28979.70.7Persons with radiation to the right arm typically had radiation across the precordium and down the left arm (137).

CAD = coronary artery disease; ECG = electrocardiography; MI = myocardial infarction.

Table Grahic Jump Location
 Laboratory and Other Studies for Diagnosis and Risk Stratification of Patients with Angina

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TestSensitivity (%)Specificity (%)Likelihood Ratio PositiveLikelihood Ratio NegativeNotes
Resting ECGMore than 50% of patients with CAD have normal resting ECGs (138). The presence of pathologic Q waves or ST-T wave abnormalities consistent with ischemia increases the likelihood of CAD (49)
Resting ECG with nonspecific ST-segment or T-wave abnormalities21%-33% of middle-aged men with angina have nonspecific ST-segment or T-wave abnormalities (46)
Resting ECG with Q-waves27% of middle-aged men with angina have Q waves (46).
Abnormal resting ECG during an episode of chest painApproximately 50% of patients with CAD will have some abnormality on an ECG obtained during an episode of chest pain. This finding suggests probable angina at a low workload and is associated with a worse prognosis (49)
Fasting lipid panel, including total cholesterol, HDL cholesterol, triglycerides, and calculated LDL cholesterolRecommended lab evaluation (49)
HemoglobinRecommended lab evaluation (49)
Fasting glucoseRecommended lab evaluation (49)
Chest X-rayEvaluate for signs of congestive heart failure or nonanginal causes of chest pain (49)
Abnormal ETT40 (men)
33 (women)
96 (men)
89 (women)
10 (men)
3 (women)
0.6 (men)
0.75 (women)
Diagnostic ETTs, controlling for referral bias (139)
Abnormal exercise echocardiography42 (men)
32 (women)
83(men)
86 (women)
2.5 (men)
2.3 (women)
0.70 (men)
0.79 (women)
Diagnostic exercise echocardiography, controlling for referral bias (140)
Abnormal ETT with SPECT thallium perfusion imaging825920.31Diagnostic ETTs with SPECT thallium imaging, controlling for referral bias (141)
Abnormal exercise or dipyridamole stress with SPECT sestamibi perfusion imaging88 (men)
87 (women)
96 (men)
91 (women)
22 (men)
9.7 (women)
0.1 (men)
0.1 (women)
Diagnostic ETTs with SPECT sestamibi, controlling for referral bias (142)
Abnormal dipyridamole stress myocardial perfusion imaging88908.80.1Summary of three studies involving 243 patients, not corrected for referral bias; this may overestimate the magnitude of the positive and negative LRs (49)
Abnormal dobutamine echocardiography79773.50.3Summary of 20 studies involving 2582 patients, not corrected for referral bias; this may overestimate the magnitude of the positive and negative LRs (49)
Electron-beam computed tomography85-100 (avg. 94)41-76 (avg. 50)1.90.1Summary of 7 studies involving 1501 patients (143). Uncertain diagnostic and prognostic accuracy, and few studies separated men from women

CAD = coronary artery disease; ECG = electrocardiography; ETT = exercise treadmill test; HDL = high-density lipoprotein; LDL = low-density lipoprotein; LR = likelihood ratio; SPECT = single photon emission computed tomography.

Table Grahic Jump Location
 Differential Diagnosis of Chest Pain

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DiseaseCharacteristics
Acute ischemic cardiovascular diseaseSubsternal chest discomfort with a characteristic quality and duration that is provoked by exertion or emotional stress and relieved by rest or nitroglycerine
Nonischemic cardiovascular disease; arrhythmiasMay cause typical angina related to increased myocardial oxygen demand and/or diminished diastolic filling of the coronary arteries.
Tachycardia
Nonischemic cardiovascular disease; valvular heart diseaseMay cause typical angina related to left ventricular outflow obstruction and increased myocardial wall stress.
Auscultation typically shows a sustained systolic murmur at the base of the heart. Aortic stenosis commonly radiates to the carotids and is associated with a weak and delayed carotid upstroke. Murmurs of subaortic hypertrophic cardiomyopathy typically increase with the Valsalva maneuver
Nonischemic cardiovascular disease; aortic dissectionClassically described as a tearing pain of abrupt onset that may radiate to the back.
In a large registry of patients with aortic dissection, abrupt onset was reported in 85%, severe pain in 91%, sharp pain in 64% (144). Blood pressure measured in both arms may show differences >10 mm Hg (this finding is neither sensitive nor specific). Chest X-ray may show a widened mediastinum or abnormal aortic contour in approximately 80% (144)
Nonischemic cardiovascular disease; pericarditisPain is often pleuritic, but may resemble angina. Classically relieved by sitting up and leaning forward.
May be associated with the presence of a friction rub on auscultation and diffuse ST-segment elevation on electrocardiogram (or PR-segment depression)
Pulmonary disease; pulmonary embolusPain is often sharp and pleuritic, and associated with dyspnea.
The presence of pulsus paradoxus, decreased oxygen saturation, and risk factors for thromboembolic disease increase the likelihood of pulmonary embolism. Syncope, hypotension, elevated neck veins, and characteristic findings on electrocardiogram are more commonly seen with large, central pulmonary embolisms
Pulmonary disease; pneumothoraxAcute onset; associated with dyspnea, pleuritic chest pain, and hyperresonance of the affected hemithorax.
Hypotension, elevated neck veins, and/or deviation of the trachea are found in hemodynamically significant tension pneumothorax
Pulmonary disease; pneumoniaFrequently associated with fever, pleuritic pain, and a productive cough
Pulmonary disease; pleuritisPleuritic chest pain
Gastrointestinal disease; esophageal (esophagitis, spasm, reflux)May be indistinguishable from angina.
Often diagnosed after a negative work-up for ischemic heart disease
Gastrointestinal disease; biliary (colic, cholecystitis, choledocholithiasis, cholangitis)Right upper-quadrant pain that radiates to the back or scapula.
Typically worse following meals. Cholangitis is suspected in the setting of fever, right upper-quadrant pain, and jaundice
Gastrointestinal disease; acid peptic diseaseMay be indistinguishable from angina, but often is related to meals
Gastrointestinal disease; pancreatitisPain is classically described as boring epigastric pain that may radiate to the back.
May be associated with systemic illness (fever, pleural effusions, hypotension, acidemia)
Chest wall or dermatologic pain; costochondritis (Tietze's syndrome)Characteristically reproduced with palpation or movement.
Reproduction with palpation does not exclude angina
Chest wall or dermatologic pain; fibrositis, rib fractureAntecedent cough or trauma
Chest wall or dermatologic pain; sternoclavicular arthritis; herpes zosterPain may precede the rash
Psychiatric disorders; anxiety disordersMay be indistinguishable from angina.
Often diagnosed after a negative work-up for ischemic heart disease. Often associated with palpitations, sweating, anxiety
Psychiatric disorders; affective disorders (e.g., depression); somatoform disorders; thought disorders (e.g., fixed delusion); factitious disorder (Munchausen's syndrome)
Table Grahic Jump Location
 Drug Treatment for Angina

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Drug or Drug ClassDosingSide EffectsPrecautionsClinical Use
FirstLineIconBeta-blockersBradycardia, hypotension, AV block, bronchospasm dizziness, drowsiness, diarrhea, nauseaAvoid with advanced AV block, sick sinus syndrome, acute HF. Avoid abrupt withdrawal. Caution with CKD, asthma, depression, elderly, hyperthyroidism
blackboxiconMetoprolol (Lopressor, Toprol-XL)Regular-release: 50-200 mg bid. Extended-release: 100-400 mg qdblackboxicon Avoid abrupt withdrawal. Decrease dose with hepatic disease. Substrate of CYP2D6
Carvedilol (Coreg, Coreg CR)Regular-release: 25-50 mg bidHyperglycemia, weight gainAvoid with hepatic disease. Substrate of CYP2D6
Acebutolol (Sectral)200-600 mg bidDecrease dose with CrCl <50. Caution with hepatic disease
Pindolol15-40 mg total daily dose, dosed tid-qidDecrease dose with severe hepatic disease
Dihydropyridine calcium-channel blockersHeadache, edema, hypotensionCaution with severe bradycardia, HF, hepatic disease, reflux esophagitis, aortic stenosisSecond-line
Amlodipine (Norvasc)5-10 mg qd
Nifedipine (Adalat CC, Procardia XL)Extended-release: 30-90 mg qdDizziness, nausea, heartburn
Non-dihydropyridine calcium-channel blockersBradycardia, hypotension, AV block, edema, dizziness, headacheAvoid with advanced AV block, sick sinus syndrome, acute HF, advanced aortic stenosis. Caution with hepatic disease, reflux esophagitis, elderly. Substrates and inhibitors of CYP3A4 and P-gpSecond-line
Diltiazem (Cardizem, Cardizem CD, Dilacor XR)Regular-release: 180-360 mg total daily dose, dosed tid-qid. Extended-release: 120-360 mg qdNausea
Verapamil (Calan, Covera-HS)Regular-release: 80-160 mg q8hr. Extended-release: 180-480 mg qhsConstipationCaution with CKD, neuromuscular disease. Substrate of CYPs: 1A2, 2C8, 2C9, 2C18
NitratesHeadache, flushing, hypotension, bradycardia, tachycardia, syncope, toleranceAvoid with severe anemia, increased intracranial pressure, closed-angle glaucoma, sildenafil. Caution with hepatic disease. Elderly should start with low doseCombined with beta-blockers or CCBs or as monotherapy in patients intolerant of other agents
Nitroglycerin (Nitrostat, NitroMist, Nitrolingual Pumpspray, Minitran, Nitrodur)Sublingual: 1 tablet (0.3 mg, 0.4 mg, or 0.6 mg) SL. May repeat q5min prn, up to 3 doses. Lingual spray or aerosol: 1-2 sprays (400-800 mcg) SL. May repeat q5min prn, up to 3 doses. 2% ointment: 15-30 mg q6-8hr. Transdermal patch: 1 patch (0.1-0.8 mg/hr) q24hr. Remove patch for 10-12 hr before next patchDermatologic reactions, methemoglobinemiaExtreme caution with suspected right ventricular infarction. Caution with constrictive pericarditis, restrictive cardiomyopathy, cardiac tamponadeAll patients should have a short-acting nitrate
Isosorbide dinitrate (Isordil, Dilatrate-SR)Immediate-release: 5-40 mg bid-tid. Sustained-release: 40-160 mg qd. SL: 2.5-5 mg prior to activityNausea
Isosorbide mononitrate (Monoket)Immediate-release: 10-20 mg bid, 7 hr apart. Extended-release: 30-60 mg qd in the AM. Maximum 120 mg qd
Other anti-anginal therapy
Ranolazine (Ranexa)500-1000 mg bidQT prolongation, headache, dizziness, hypotension, nausea, constipation,Avoid with hepatic cirrhosis, severe CKD, CYP3A inducers or potent inhibitors. Caution with mild-moderate CKD, hepatic disease. Use low dose with moderate CYP3A inhibitors. Substrate and inhibitor of CYP2D6 and P-gpInadequate response or intolerance to other agents
Platelet inhibitors
Aspirin75-325 mg qdNausea, dyspepsia, abdominal pain, hypersensitivity reactions, bleedingAvoid with severe hepatic disease or severe CKD. Caution with asthma, GI diseaseAll patients without a contraindication
blackboxiconClopidogrel (Plavix)75 mg qdBleeding, diarrhea, rare TTPblackboxicon Diminished effect in poor metabolizers. Avoid use of omeprazole or esomeprazole. Caution with hepatic diseaseFor patients with aspirin contraindication
blackboxiconPrasugrel (Effient)60 mg loading dose, then 10 mg qdBleeding, bradycardia, hypotension, hypertension, hyperlipidemia, hypercholesterolemia, TTP, hypersensitivity reactions, nauseablackboxicon Bleeding risk. If <60 kg, reduce dose to 5 mg qd. Avoid if >75 years. Avoid with history of TIA or stroke. Caution with severe hepatic disease
blackboxiconTicagrelor (Brilinta)180 mg loading dose, then 90 mg bidDyspnea, headache, dizzinessblackboxicon Bleeding risk. Maintenance doses of aspirin >100 mg reduce effectiveness of ticagrelor. Avoid with severe hepatic impairment. Caution with moderate hepatic impairment. Many drug interactions due to CYP3A4 metabolism and inhibition, and P-gp inhibitionDo not combine with more than 81 mg aspirin daily
HMG-CoA reductase inhibitors (statins)Generally more effective if given at bedtimeConstipation, abdominal pain, nausea, rhabdomyolysis, nephrotoxicity, myalgia, myopathy, hepatotoxicity, diabetes. Rare: hypersensitivity reactions, neuropathyAvoid with hepatic disease, pregnancy, cyclosporine, gemfibrozil. Caution with fenofibrate, niacin, elderly. Most statins have additional CYP450 drug interactions. Avoid >1 quart/day grapefruit juiceAll patients who tolerate
Atorvastatin (Lipitor)Intensity: High: 40-80 mg qd
Moderate: 10-20 mg qd
If taking a CYP3A4 inhibitor, maximum dose 20 mg qd
Lovastatin (Mevacor)Intensity:
Moderate: 40 mg qd
Low: 20 mg qd
Give with PM meal
If CrCl <30, maximum dose 20 mg qd. Avoid CYP3A4 inhibitors. Maximum daily dose 20 mg with fibrates, niacin, danazol, cyclosporine; or 40 mg immediate-release with amiodarone, verapamil
Rosuvastatin (Crestor)Intensity:
High: 20-40 mg qd
Moderate: 5-10 mg qd
Can be taken in AM or PM
If CrCl <30, maximum dose 10 mg qd. Undergoes minimal hepatic metabolism. Use 5 mg starting dose with Asians
Simvastatin (Zocor)Intensity:
Moderate: 20-40 mg qd
Low: 10 mg qd
If CrCl <20, start with 5 mg qhs. Avoid CYP3A4 inhibitors. Maximum daily dose 5-10 mg with diltiazem, dronedarone, verapamil; or 5-20 mg with amiodarone, amlodipine, ranolazine. Caution with >20 mg in Chinese
blackboxiconAngiotensin- converting enzyme inhibitorsHypotension, cough, hyperkalemia, angioedema, anaphylactoid reactionsblackboxicon Pregnancy. Avoid if history of angioedema. Caution with aortic stenosisAll patients without contraindications
blackboxiconEnalapril (Vasotec)2.5 mg qd-20 mg bidRequires hepatic activation. Decrease dose with CrCl <30
blackboxiconLisinopril (Prinivil, Zestril)5-40 mg qdDecrease dose with: elderly, CrCl <30
blackboxiconRamipril (Altace)1.25-20 mg total daily dose, dosed qd-bidDecrease dose with CrCl <40
blackboxiconQuinapril (Accupril)5-80 mg total daily dose, dosed qd-bidDecrease dose with CrCl <90

FirstLineIcon = first-line agent; blackboxicon = black box warning; AM = morning; AV = atrioventricular; bid = twice daily; CCB = calcium-channel blocker; CKD = chronic kidney disease; CrCl = creatinine clearance; CYP = cytochrome P450 isoenzyme; GI = gastrointestinal; HF = heart failure; HMG-CoA = hydroxymethylglutaryl-coenzyme A; P-gp = P-glycoprotein; PM = evening; prn = as needed; q6-8hr = every 6-8 hours; q8hr = every 8 hours; q24hr = every 24 hours; q5m = every 5 minutes; qd = once daily; qhs = every day at bedtime; qid = four times daily; SL = sublingual; TIA = transient ischemic attack; tid = three times daily; TTP = thrombotic thrombocytopenic purpura.

ACP Smart Medicine provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

Table Grahic Jump Location
 Choice of Diagnostic Stress Test

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Exercise ECG without imaging
Obtain in patients with an intermediate probability of CAD who are able to exercise, including patients with <1 mm ST depression or complete right bundle-branch block on a resting ECG
Exercise ECG is accurate in patients with complete right bundle-branch block (a positive test result is indicated by exercise-induced ST-segment depression in the inferior leads or lateral precordium) or <1 mm of baseline ST-segment depression on the resting ECG
Left ventricular hypertrophy with repolarization abnormality on the resting ECG reduces the specificity of exercise treadmill testing
Digoxin often causes ST-segment depression and reduces the specificity of exercise treadmill testing
Hold β-blockers and nitrates for approximately 48 hours (4 to 5 half-lives) when feasible before diagnostic exercise treadmill testing
Exercise ECG with myocardial perfusion imaging or exercise echocardiography
Obtain in patients with an intermediate probability of CAD who are able to exercise and have one of the following baseline ECG abnormalities:
Pre-excitation (Wolff-Parkinson-White) syndrome
More than 1 mm of ST depression
Also appropriate in patients who are able to exercise with an intermediate pretest probability of CAD and have a history of previous revascularization (PCI or CABG)
May be preferable studies in patients who take digoxin or have LVH with less than 1 mm of ST depression at rest
Exercise echocardiography is an acceptable choice in patients with left bundle-branch block on resting ECG
Pharmacologic stress myocardial perfusion imaging or dobutamine echocardiography
Obtain in patients with an intermediate pretest probability of CAD and
An electronically paced ventricular rhythm; or
Left bundle-branch block (exercise stress testing is associated with an increase in false-positive test results)
Also appropriate in patients with an intermediate pretest probability of CAD who are unable to exercise
Notes:
Stress imaging is recommended to further stratify patients with intermediate risk diagnostic exercise treadmill test results
Exercise (treadmill or bicycle ergometer) is preferred to pharmacologic stress in most instances; it provides the most information regarding symptoms, cardiovascular reserve, and hemodynamic response during activity
Exercise or pharmacologic stress testing is safe in low-risk outpatients with unstable angina and in low- or intermediate-risk inpatients with unstable angina who have had an acute MI ruled out, are angina-free at rest, and do not have symptomatic heart failure (49)

CABG = coronary artery bypass grafting; CAD = coronary artery disease; ECG = electrocardiography; LVH = left ventricular hypertrophy; MI = myocardial infarction; PTCA = percutaneous transluminal coronary angiography.

Table Grahic Jump Location
 Example of Estimation of Mortality Risk Using the Duke Treadmill Score

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A 55-year-old man with atypical angina and no other risk factors has a 50% pretest probability of significant CAD and a post-test probability of 37.5%
Although this result does not exclude the possibility of significant CAD, the treadmill results convey important prognostic information; on exercise treadmill testing, he exercised for 12 minutes and developed 1 mm ST-segment depression in his lateral precordium. He had no chest pain. His DTS = 12 [minutes of exercise] - 5 [5 × the ST-deviation] - 0 [4 × angina score] = +7. This is a low-risk score that corresponds to an estimated annual mortality of 0.25% over the following 4 years
It is therefore possible to avoid additional testing for the purposes of risk stratification
Had the same patient exercised for 7 minutes before developing 2 mm ST-segment depression and angina that resulted in stopping the test, his DTS would = 7 - (5 × 2) - (4 × 2) = -11. This is a high-risk score that corresponds to an estimated annual mortality of 5% over the following 4 years
This result would warrant referral for coronary angiography and evaluation for possible revascularization
Similarly, a 55-year-old man with typical angina and no other risk factors has a pretest probability of CAD of 80%. A normal result on an exercise treadmill test would not exclude the diagnosis of CAD (the post-test probability would be approximately 70%, but would be important in determining whether to recommend proceeding directly to coronary angiography

CAD = coronary artery disease; LR+= Positive likelihood ratio LR-= Negative likelihood ratio SPECT = single photon emission computed tomography.

Table Grahic Jump Location
 Examples of Diagnostic Usefulness of Noninvasive Functional Studies

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For example, a 55-year-old man with atypical angina and no other risk factors has a 50% pretest probability of significant CAD (i.e., 70% or greater stenosis in one or more major epicardial arteries) (60). The pretest odds of significant CAD are 0.5/0.5 = 1
An abnormal exercise treadmill test (LR+ = 10) would result in post-test odds of 10 or a posterior probability of 10/11 = 91% probability of CAD
A normal exercise treadmill test (LR- = 0.6) would result in post-test odds of 0.6 in a posterior probability of 0.6/1.6 = 37.5% probability of CAD
An abnormal exercise treadmill test with SPECT sestamibi scintigraphy (LR+ = 22) would result in post-test odds of 22 or a posterior probability of 22/23 = 96% probability of CAD
A normal exercise treadmill test with SPECT sestamibi scintigraphy (LR- = 0.13) would result in post-test odds of 0.13 or a posterior probability of 0.13/1.13 = 11% probability of CAD
Noninvasive functional studies are of little value for diagnosing CAD in patients with a high pretest probability of CAD. In this circumstance, a negative test result is more likely to be falsely than truly negative. For example, a 55-year-old man with typical angina and no other risk factors has an 80% pretest probability of significant CAD (60). The pretest odds of significant CAD are 0.8/0.2 = 4
An abnormal exercise treadmill test would result in a posterior probability of 98% probability of CAD
A normal exercise treadmill test would result in a posterior probability of 71% probability of CAD
An abnormal exercise treadmill test with SPECT sestamibi scintigraphy would result in a posterior probability of 99% probability of CAD
A normal exercise treadmill test with SPECT sestamibi scintigraphy would result in a posterior probability of 33% probability of CAD
Noninvasive functional studies are of little value for diagnosing CAD in patients with a low pretest probability of CAD. In this circumstance, a positive test result is often more likely to be falsely than truly positive. For example, a 45-year-old woman with atypical angina and no other risk factors has a 5% pretest probability of significant CAD (60). The pretest odds of significant CAD are 0.05/0.95 = 0.05
An abnormal exercise treadmill test would result in a posterior probability of 14% probability of CAD
A normal exercise treadmill test would result in a posterior probability of 4% probability of CAD
An abnormal exercise treadmill test with SPECT sestamibi scintigraphy would result in a posterior probability of 33% probability of CAD
A normal exercise treadmill test with SPECT sestamibi scintigraphy would result in a posterior probability of < 1% probability of CAD

CAD = coronary artery disease; SPECT = single photon emission computed tomography.

Table Grahic Jump Location
 Post-test Probability of Significant Coronary Artery Disease After Various Functional Studies, Corrected for Referral Bias Unless Indicated

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ResultPretest Probability (%)
205080
Abnormal exercise treadmill test, men (139)719198
Abnormal exercise treadmill test, women (139)437592
Normal exercise treadmill test, men (139)133871
Normal exercise treadmill test, women (139)164375
Abnormal exercise treadmill test with SPECT thallium scintigraphy (141)336789
Normal exercise treadmill test with SPECT thallium scintigraphy (141)72355
Abnormal exercise or dipyridamole stress test with SPECT sestamibi scintigraphy, men (142)859699
Abnormal exercise or dipyridamole stress test with SPECT sestamibi scintigraphy, women (142)719198
Normal exercise or dipyridamole or stress test with SPECT sestamibi scintigraphy, men (142)31133
Normal exercise or dipyridamole or stress test with SPECT sestamibi scintigraphy, women (142)41336
Abnormal exercise echocardiography, men (140)387191
Abnormal exercise echocardiography, women (140)377082
Normal exercise echocardiography, men (140)154174
Normal exercise echocardiography, women (140)174476
Abnormal dipyridamole stress myocardial perfusion imaging. Unadjusted for referral bias; this may overestimate the predictive value of an abnormal test (49)699097
Normal dipyridamole stress myocardial perfusion imaging. Unadjusted for referral bias; this may overestimate the predictive value of a normal test (49)31235
Abnormal dobutamine echocardiography. Unadjusted for referral bias; this may overestimate the predictive value of an abnormal test (49)467793
Normal dobutamine echocardiography. Unadjusted for referral bias; this may overestimate the predictive value of a normal test (49)31132

SPECT = single photon emission computed tomography.

Table Grahic Jump Location
 Post-test Probability of Significant Coronary Artery Disease After Electron-beam CT in Adults

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ResultPretest Probability (%)
205080
Abnormal electron-beam CT (143)326688
Normal electron-beam CT (143)31132

CT = computed tomography

Table Grahic Jump Location
 Post-test Probabilities of Significant Coronary Artery Disease Based on Exercise Electrocardiogram Results

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ResultPretest Probability (%)
205080
ST depression <0.5 mm51944
ST depression 0.5-0.99 mm194879
ST depression 1.0-1.49 mm346889
ST depression 1.5-1.99 mm518194
ST depression 2.0-2.49 mm739298
ST depression ≥2.5 mm9198>99
Table Grahic Jump Location
 Contraindications and Reasons to Terminate Stress Tests

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Absolute contraindications for exercise testing include
Acute MI within the past 2 days
Arrhythmias causing symptoms or hemodynamic compromise
Symptomatic and severe asymptomatic aortic stenosis
Symptomatic heart failure
Acute pulmonary embolus or pulmonary infarction
Acute myocarditis or pericarditis
Acute aortic dissection
Relative contraindications for exercise testing include
Left-main coronary stenosis
Moderate aortic stenosis
Electrolyte abnormalities
Systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg
Tachyarrhythmias or bradyarrhythmias
Hypertrophic cardiomyopathy or other forms of ventricular outflow obstruction
Mental or physical impairment resulting in an inability to exercise
High-degree atrioventricular block
Absolute indications for stopping an exercise treadmill test
Drop in systolic blood pressure >10 mm Hg when accompanied by other signs of ischemia
Moderate to severe angina
Increasing ataxia, dizziness, or near syncope
Signs of poor perfusion, such as pallor or cyanosis
Technical difficulties monitoring the ECG or systolic blood pressure
The subject's desire to stop
Sustained ventricular tachycardia
ST elevation ≥1 mm in leads without diagnostic Q waves (other than V1 or aVR)
Relative indications for stopping include
Drop in systolic blood pressure >10 mm Hg in the absence of other evidence of ischemia
2 mm of horizontal or downsloping ST-segment depression
Marked axis deviation
Arrhythmias, such as multifocal PVCs, triplets of PVCs, supraventricular tachycardia, heart block or bradyarrhythmias
Fatigue, shortness of breath, wheezing, leg cramps, or claudication
Exercise-induced bundle-branch block or intraventricular conduction delay that cannot be distinguished from ventricular tachycardia (e.g., fast wide rhythm)
Increasing chest pain
Systolic blood pressure >250 mm Hg or diastolic blood pressure >115 mm Hg

ECG = electrocardiography; MI = myocardial infarction; PVC= premature ventricular contraction.

Table Grahic Jump Location
 Risk for Mortality at 1 Year: Clinical History Variables

Swipe to view table

1. Find points for each risk factor:
Age (yr)PointsPain typePointsComorbid FactorPoints*
200Nonanginal pain3CVD20
3013Atypical angina25PVD23
4025Typical anginaDiabetes20
5038Stable41Previous MI17
6050Progressive46Hypertension8
7062Unstable51Mild mitral regurgitation19
8075Severe mitral regurgitation38
9088
100100
2. Sum points for all risk factors:
Age + Pain score + Comorbidity = Point total
3. Look up risk corresponding to point total:
Total PointsProbability of 1-year Death
841%
1062%
1203%
1365%
16010%
18420%
19930%
21140%
22050%
22960%

CVD = cerebrovascular disease; MI = myocardial infarction; PVD = peripheral vascular disease.

* Zero points for each “no.”

Clinical examples: 60-year-old man with stable angina: 1%-2% mortality at 1 year; 60-year-old man with stable angina and a history of MI: <3% mortality at 1 year; 60-year-old man with progressive angina, a history of MI, peripheral vascular disease, hypertension, and diabetes: 10%-20% mortality at 1 year.

From 61.

Table Grahic Jump Location
 Clinical Classification of Chest Pain

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Typical (Definite) Angina
1.Substernal chest discomfort with a characteristic quality and duration that is,
2.Provoked by exertion or emotional stress and
3.Relieved by rest or nitroglycerin
Atypical (Probable) Angina
Meets 2 of the above criteria
Typical (Definite) Angina
Meets ≤1 of the typical angina criteria

Adapted from Diamond (1979 and 1983) (57; 145).

Table Grahic Jump Location
 Therapeutic Intensity of Statin Doses*

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DrugHigh-Intensity DosingModerate-Intensity DosingLow-Intensity Dosing
Atorvastatin40-80 mg10-20 mg
Flusvastatin80 mg (or 40 mg bid)10-20 mg
Lovastatin40 mg20 mg
Pitavastatin2-4 mg1 mg
Pravastatin40-80 mg10-20 mg
Rosuvastatin20-40 mg5-10 mg
Simvastatin†80 mg†20-40 mg10mg

bid = twice daily.

*Adapted from (40).

†Not recommended by the FDA.

  • Coronary Angiogram Radiocontrast dye is injected via catheter (arrow) during coronary angiography, demonstrating 85% to 90% occlusion of the mid-right coronary artery (asterisk).
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AABB

formerly, the American Association of Blood Banks

ACC

American College of Cardiology

ACCF

American College of Cardiology Foundation

ACE

angiotensin-converting enzyme

ACP

American College of Physicians

ADA

American Diabetes Association

AHA

American Heart Association

ARB

angiotensin receptor blocker

ARR

absolute risk reduction

ASCVD

atherosclerotic cardiovascular disease

AV

atrioventricular

CABG

coronary artery bypass graft(ing

CAD

coronary artery disease

CHD

coronary heart disease

CHF

congestive heart failure

CI

confidence interval

COX-1

cyclooxygenase-1

CPR

cardiopulmonary resuscitation

CRT

cardiac resynchronization therapy

CT

computed tomography

ECG

electrocardiography/electrocardiogram

GI

gastrointestinal

HDL

high-density lipoprotein

HF

heart failure

HIV

human immunodeficiency virus

HR

hazard ratio

ICD

implantable cardioverter defibrillator

IFG

impaired fasting glucose

IGT

impaired glucose tolerance

JNC 8

Eighth Joint National Committee

LDL

low-density lipoprotein

LV

left ventricle

LVEF

left ventricular ejection fraction

MET

metabolic equivalent

MI

myocardial infarction

NCEP

National Cholesterol Education Program

NICE

National Institute for Health and Care Excellence

NNH

number needed to harm

NNT

number needed to treat

NYHA

New York Heart Association

OR

odds ratio

PCI

percutaneous coronary intervention

PET

positron emission tomography

RCT

randomized, controlled trial

RR

relative risk

SPECT

single-photon emission computed tomography

STEMI

ST-elevation myocardial infarction

TSH

thyroid-stimulating hormone

UA/NSTEMI

unstable angina/non-ST-elevation myocardial infarction

USPSTF

U.S. Preventive Services Task Force

VF

ventricular fibrillation

VT

ventricular tachycardia

YAG

yttrium-aluminum garnet


Study Name Acronyms
CAPRIE

Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events

CASS

Coronary Artery Surgery Study

CONSENSUS

Cooperative North Scandinavian Enalapril Survival Study

COURAGE

Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation

HOPE

Heart Outcome Prevention Evaluation

MRFIT

Multiple Risk Factor Intervention Trial

ONTARGET

Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial

PLATO

Platelet Inhibition and Patient Outcomes

SOLVD

Studies of Left Ventricular Dysfunction

TIMI

Thrombolysis in Myocardial Infarction (criteria)

TRITON

Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel


Preventive Cardiovascular Nurses Assocation: Angina

Preventive Cardiovascular Nurses Association: Women and Heart Disease

American College of Cardiology: Coronary Artery Disease

Agency for Healthcare Research and Quality: “ACE Inhibitors” and “ARBs” To Protect Your Heart?

American Academy of Family Physicians: Angina

American College of Physicians: Five Keys to a Healthy Heart: A Guide for African Americans

American Heart Association: Symptoms and Diagnosis of Heart Attack

Consumer Reports: Your Guide to a Healthy Heart

Consumer Reports Best Buy Drugs: Evaluating Statin Drugs to Treat High Cholesterol and Heart Disease

Consumer Reports Best Buy Drugs: Using ACE Inhibitors to Treat High Blood Pressure and Heart Disease

Consumer Reports Best Buy Drugs: Using Antiplatelet Drugs to Treat Heart Disease, Heart Attacks, and Strokes

Consumer Reports Best Buy Drugs: Using Beta Blockers to Treat High Blood Pressure and Heart Disease

Consumer Reports Best Buy Drugs: Using Calcium Channel Blockers to Treat High Blood Pressure and Heart Disease

National Heart, Lung and Blood Institute: Heart and Vascular Diseases

National Heart, Lung, and Blood Institute: What Is Angina?

Office on Women's Health: Heart Health and Stroke

Agency for Healthcare Research and Quality: “ACE Inhibitors” and “ARBs” To Protect Your Heart? (Spanish)

Consumer Reports Best Buy Drugs: Evaluating Statin Drugs to Treat High Cholesterol and Heart Disease (Spanish)

Consumer Reports Best Buy Drugs: Using ACE Inhibitors to Treat High Blood Pressure and Heart Disease (Spanish)

Consumer Reports Best Buy Drugs: Using Antiplatelet Drugs to Treat Heart Disease, Heart Attacks, and Strokes (Spanish)

Consumer Reports Best Buy Drugs: Using Beta Blockers to Treat High Blood Pressure and Heart Disease (Spanish)

Consumer Reports Best Buy Drugs: Using Calcium Channel Blockers to Treat High Blood Pressure and Heart Disease (Spanish)

Office on Women's Health: Heart Health and Stroke (Spanish)

DOI: 10.7326/d032
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
Author(s) and Disclosures:
Paul R. Sutton, MD, PhD has nothing to disclose. Stephan D. Fihn, MD, MPH has nothing to disclose. Vera Bittner, MD, MSPH is involved in studies for University of Alabama at Birmingham that received research grants and contracts from Amgen, Bayer Healthcare, Janssen Pharma, Pfizer, Sanofi, and AstraZeneca and has consultantships with Amgen and Eli Lilly. Gautam Reddy, MD has nothing to disclose.

One or more of the present or past ACP Smart Medicine physician editors worked on this module and had nothing to disclose: Davoren Chick, MD, FACP; Deborah Korenstein, MD, FACP; Marjorie Lazoff, MD; Richard Lynn, MD, FACP.

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