Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II–Receptor Blockers for Ischemic Heart Disease

Abstract

Background: Patients with ischemic heart disease and preserved ventricular function experience considerable morbidity and mortality despite standard medical therapy.

Purpose: To compare benefits and harms of using angiotensin-converting enzyme (ACE) inhibitors, angiotensin II–receptor blockers (ARBs), or combination therapy in adults with stable ischemic heart disease and preserved ventricular function.

Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (earliest date, July 2009) were searched without language restrictions.

Study Selection: Two independent investigators screened citations for trials of at least 6 months' duration that compared ACE inhibitors, ARBs, or combination therapy with placebo or active control and reported any of several clinical outcomes.

Data Extraction: Using standardized protocols, 2 independent investigators extracted information about study characteristics and rated the quality and strength of evidence. Disagreement was resolved by consensus.

Data Synthesis: 41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32 559 participants) showed that ACE inhibitors reduce the relative risk (RR) for total mortality (RR, 0.87 [95% CI, 0.81 to 0.94]) and nonfatal myocardial infarction (RR, 0.83 [CI, 0.73 to 0.94]) but increase the risk for syncope (RR, 1.24 [CI, 1.02 to 1.52]) and cough (RR, 1.67 [CI, 1.22 to 2.29]) compared with placebo. Low-strength evidence (1 trial; 5926 participants) suggested that ARBs reduce the RR for the composite end point of cardiovascular mortality, nonfatal myocardial infarction, or stroke (RR, 0.88 [CI, 0.77 to 1.00]) but not for the individual components. Moderate-strength evidence (1 trial; 25 620 participants) showed similar effects on total mortality (RR, 1.07 [CI, 0.98 to 1.16]) and myocardial infarction (RR, 1.08 [CI, 0.94 to 1.23]) but an increased risk for discontinuations because of hypotension (P < 0.001) and syncope (P = 0.035) with combination therapy compared with ACE inhibitors alone.

Limitations: Many studies either did not assess or did not report harms in a systematic manner. Many studies did not adequately report benefits or harms by various patient subgroups.

Conclusion: Adding an ACE inhibitor to standard medical therapy improves outcomes, including mortality and myocardial infarctions, in some patients with stable ischemic heart disease and preserved ventricular function. Combination therapy seems no better than ACE inhibitor therapy alone and increases harms.

Primary Funding Source: University of Connecticut/Hartford Hospital Evidence-based Practice Center and the Agency for Healthcare Research and Quality.