Summary of AHRQ's comparative effectiveness review of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers added to standard medical therapy for treating stable ischemic heart disease

Abstract

Background: Standard therapies for the management of stable ischemic heart disease (IHD) partially reduce the risk of a future acute coronary syndrome. Among patients with chronic heart failure or previous myocardial infarction and left ventricular dysfunction, a large body of evidence supports the benefits of angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARBs) and, in heart failure, combined therapy with these agents. In contrast, there is less certainty regarding outcomes of ACE inhibitors and ARBs for people with stable IHD who have preserved left ventricular function and no signs or symptoms of heart failure. To compile and synthesize findings derived from research on this specific population, the Agency for Healthcare Research and Quality (AHRQ) commissioned and, in October 2009, published a systematic review and meta-analysis on the benefits and harms of ACE inhibitors and ARBs.

Objectives: To (a) familiarize health care professionals with AHRQ’s 2009 systematic review on ACE inhibitors and ARBs for people with stable IHD and preserved left ventricular function, (b) provide commentary and encourage consideration of the clinical and managed care applications of the review findings, and (c) identify limitations to the existing research on the benefits and harms of ACE inhibitors and ARBs.

Summary: Six trials meeting eligibility criteria provided moderate to strong evidence that, compared with standard therapies alone, ACE inhibitors significantly lower the risks of total mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), stroke, and other clinical outcomes. However, study participants on ACE inhibitors had higher incidences of withdrawals due to adverse events, including syncope, cough, and hyperkalemia. Only 1 trial (TRANSCEND) met eligibility criteria for comparing standard therapies alone versus an ARB (telmisartan). No significant differences were observed for individual clinical endpoints across groups in TRANSCEND, although the composite measure (cardiovascular mortality, nonfatal MI, and stroke) was significantly lower for telmisartan compared with placebo; like ACE inhibitors, ARB therapy increased the risk of hyperkalemia. Only 1 trial (ONTARGET) was identified that compared an ACE inhibitor (ramipril) with an ARB (telmisartan), and this trial showed that ramipril and telmisartan have similar efficacy, similar risks of harms, and therefore a similar balance of benefits to harms. ONTARGET showed that the risk reduction for all clinical endpoints was similar across the 3 treatment arms (ramipril, telmisartan, and combination therapy with ramipril and telmisartan). Combination therapy in ONTARGET was associated with a greater number of total study discontinuations, including discontinuations due to hypotension and syncope. Telmisartan compared with ramipiril had lower rates of cough and angioedema and a higher rate of hypotensive symptoms; there was no difference between ramipril and telmisartan in the rate of syncope. This summary of the AHRQ review also describes the benefits and harms of ACE inhibitors and ARBs in patients who recently had, or were scheduled to have, a revascularization procedure and in different patient subpopulations.