Nearly 2,400 Americans die of cardiovascular disease each day. Cardiovascular disease claims more lives each year than cancer, chronic lower respiratory diseases, accidents, and diabetes mellitus combined. American College of Cardiology and American Heart Association guidelines support the use of angiotensin converting enzyme (ACE) inhibitors in patients who have chronic heart failure or those with myocardial infarction and left ventricular dysfunction, while angiotensin receptor blockers (ARBs) are reserved for those who cannot tolerate ACE inhibitors. Combined ACE inhibitor and ARB therapy has been shown to provide additional benefits over therapy with an ACE inhibitor alone among patients with heart failure. However, the combined use of an ACE inhibitor and ARB in post-myocardial-infarction patients with left ventricular dysfunction or heart failure was no better than the use of captopril alone and carried an increased risk of harms. This report summarizes the available evidence comparing the efficacy and safety of using ACE inhibitors, ARBs, or their combination vs. standard medical therapy in a population with stable ischemic heart disease, or an ischemic heart disease risk equivalent, and preserved left ventricular function. This report addresses the following questions: KQ1. What is the comparative effectiveness of ACE inhibitors or ARBs added to standard medical therapy when compared to standard medical therapy alone in terms of total mortality, cardiovascular mortality, nonfatal myocardial infarction, stroke, the composite endpoint of the latter three items, and atrial fibrillation? What is the evidence of benefit on other outcomes such as symptom reporting, hospitalization, revascularization, and quality of life measures? KQ2. In patients who are receiving standard medical therapy, what is the comparative effectiveness of combining ACE inhibitors and ARBs vs. either an ACE inhibitor or ARB alone in terms of total mortality, cardiovascular mortality, nonfatal myocardial infarction, stroke, the composite endpoint of the latter three items, and atrial fibrillation? What is the evidence of benefit on other outcomes such as symptom reporting, hospitalization, revascularization, and quality of life measures? KQ3. In patients who had to have recently undergone, or are set to undergo, a coronary revascularization procedure, what is the comparative effectiveness of ACE inhibitors or ARBs added to standard medical therapy when compared to standard medical therapy alone in terms of total mortality, cardiovascular mortality, nonfatal myocardial infarction, stroke, the composite endpoint of the latter three items, and atrial fibrillation? What is the evidence of benefit on other outcomes such as symptom reporting, hospitalization, revascularization, and quality of life measures? KQ4. What are the comparative harms of adding ACE inhibitors or ARBs to standard medical therapy when compared to standard medical therapy alone? KQ5. In patients receiving standard medical therapy, what is the evidence of comparative harms of combination ACE inhibitor and ARB therapy vs. use with either an ACE inhibitor or ARB alone? KQ6. In patients who had to have recently undergone, or are set to undergo, a coronary revascularization procedure, what are the comparative harms of ACE inhibitors or ARBs added to standard medical therapy when compared to standard medical therapy alone? KQ7. What is the evidence that benefits or harms differ by subpopulations, including: demographics, clinical course, dose of the ACE inhibitor or ARB used, comorbidities, and other medications?
