Renin–Angiotensin System Antagonists and Clinical Outcomes in Stable Coronary Artery Disease Without Heart Failure

Study Questions:

Is use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II receptor blocker (ARB) associated with lower rates of cardiovascular events in patients with stable coronary artery disease (CAD), but without heart failure (HF)?


This was a retrospective analysis of the Reduction of Atherothrombosis for Continued Health (REACH) registry. Using propensity score approaches, the authors determined relationships between cardiovascular outcomes and ACEI/ARB use (64.1% users) in 20,909 outpatients with stable CAD and free of HF at baseline. The primary outcome of REACH was the composite of cardiovascular death, myocardial infarction (MI), or stroke during 4-year follow-up.


In matched cohorts, the rate of the primary outcome was similar in ACEI/ARB users compared with nonusers (adjusted hazard ratio, 1.03; 95% confidence interval, 0.90-1.19; p = 0.66). There was a borderline interaction between a history of recent MI (≤1 year) and the effect of ACEI/ARB (p = 0.06); this heterogeneity did not persist in the propensity-score matched cohorts.


The authors concluded that the use ACEI/ARB in outpatients with stable CAD and without HF is not associated with improved cardiovascular outcomes.


This is an important study that builds on the observation that not all clinical trials have demonstrated that ACEI improve cardiovascular outcomes in patients with stable CAD and preserved left ventricular function. The PEACE and IMAGINE trials found no impact of ACEI in patients with stable CAD or recent coronary artery bypass grafting and without HF. The findings from this retrospective analysis of the large, international, and contemporary cohort would corroborate these findings. The authors acknowledge that there was lack of information regarding doses of ACEI/ARB, and that effective doses of these medications are often higher than those used in clinical practice. Nonetheless, this analysis would suggest a limited role for therapy with ACEI/ARB in patients with stable CAD and free of HF. There may be a benefit in those with recent MI, and this warrants further investigation.

Clinical Topics: Atherosclerotic Disease (CAD/PAD)

Keywords: Coronary Artery Disease, Myocardial Infarction, Stroke, Angiotensin II Type 1 Receptor Blockers

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