Abstract 19292: The Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients with Coronary Artery Disease and No Heart Failure in the Modern Statin Era: a Meta-Analysis of Randomized-Controlled Trials

Abstract

Background: Data from randomized-controlled trials regarding the efficacy of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in patients with coronary artery disease (CAD) but no evidence of heart failure are inconclusive. Current ACC/AHA guidelines support their use in this population. The variation in efficacy of ACEi and ARBs in improving cardiovascular (CV) outcomes may be related to the rising use of statin therapy in the past two decades. Methods: We conducted literature review of randomized-controlled trials with ACEi or ARBs as the single intervention, focusing on studies involving patients with CAD including patients with left ventricular dysfunction but no clinical symptoms of heart failure. The MEDLINE database was searched for publications between 1/1/1980 and 12/31/2012 with searched terms including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, coronary artery disease, cardiovascular events, and myocardial infarction. Of the 1553 potentially relevant publications, 19 (14 ACEi and 5 ARB) met the inclusion criteria for a total of 99,631 randomized patients followed for a mean of 38 months. We evaluated the endpoints of CV mortality, all-cause mortality, non-fatal MI, and stroke. The relationship between endpoints across the 19 trials and the percentage of patients on statins in each trial (with available data) were evaluated using meta-regression analysis, expressed as highest standardized regression coefficient, Beta. Results: ACEi and ARB therapy across the 19 trials was associated with decreased CV mortality (OR 0.85; 95% CI 0.78-0.93) and all-cause mortality (OR 0.92; 95% CI 0.86-0.98). When adjusted for the percentage of statin, 46% of patients in the cohort, there was a significant linear decrease in the odds of CV mortality reduction with ACEi and ARB therapy (Beta = 0.01; p = 0.034). Conclusion: In patients with CAD and no evidence of heart failure, the additive benefits of ACEi and ARBs in decreasing CV mortality are blunted by statin therapy. The exact mechanism(s) for this result is unclear and further investigation is warranted. The modification of current ACC/AHA practice guidelines should be considered.