Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers in Coronary Artery Disease without Heart Failure in the Modern Statin Era: a Meta-Analysis of Randomized-Controlled Trials

Purpose: Current practice guidelines support the use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) in patients with coronary artery disease (CAD) without heart failure (HF). However, a number of cited trials were performed prior to the era of prevalent statin use. Our objective was to evaluate the effectiveness of ACEi and ARBs in reducing cardiovascular events as well as the impact of statin therapy. Methods: We searched the MEDLINE and EMBASE databases for randomized-controlled trials (1/1/1980 – 8/31/2015) with ACEi or ARBs as the single intervention for patients with CAD without HF. We assessed the outcomes of non-fatal myocardial infarction (MI), stroke, cardiovascular mortality and all-cause mortality. The relationship between these outcomes and the percentages of patients on statin therapy was evaluated using meta-regression analysis. Results: A total of ten ACEi trials and five ARB trials were included for analysis, with 78,761 patients followed for a mean of 36 months. Treatment with ACEi was associated with decreased non-fatal MI (RR 0.83; 95 % CI 0.75–0.91), stroke (RR 0.76; 95 % CI 0.68–0.86), cardiovascular mortality (RR 0.83; 95 % CI 0.72–0.95), and all-cause mortality (RR 0.86; 95 % CI 0.80–0.93). Treatment with ARBs was associated only with a decreased incidence of stroke (RR 0.92; 95 % CI 0.87–0.98). When adjusted for statin use, there was a trend towards an attenuated effect of ACEi in reducing cardiovascular mortality with increased use of statins (p-value = 0.063). Conclusion: In CAD patients without HF, ACEi, but not ARBs decreases the risk of non-fatal MI, cardiovascular mortality and all-cause mortality, while both ACEi and ARBs decrease the risk of stroke.