Meta-Analysis of Renin-Angiotensin-Aldosterone Blockade for Heart Failure in Presence of Preserved Left Ventricular Function

Abstract

Background: Heart failure (HF) with a preserved left ventricular (LV) ejection fraction (EF) is the leading cause of hospitalization after 65 years of age. Individual randomized trials have not shown benefits conferred by angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARB) in these patients. To overcome this limitation, we performed a meta-analysis of the randomized trials of ACE inhibitors or ARB in patients with HF and preserved LVEF. Methods: Our search identified 4 randomized trials, comprising a total of 8152 patients, that investigated the effects of ACE inhibitors (n = 1), ARB (n = 2), or both treatments (n = 1). Risk ratios (RR) and 95% confidence intervals (CI) were calculated using a fixed-effect estimate method in the randomised trials. Results: Compared with placebo or no treatment, treatment with ACE inhibition or ARB was associated with lower rates of hospitalization for HF (RR 0.90; 95% CI 0.81-0.99, P = .032), though not cardiovascular mortality (RR 1.01; 95% CI 0.90-1.13, P = 0.858). In 3 studies where these endpoints were combined, the 1-year incidence of cardiovascular death or hospitalization for HF was lowered by ACE inhibition or ARB (RR 0.74; 95% CI 0.58-0.94, P = .014). Conclusion: Compared with placebo, ACE inhibition or ARB significantly lowered risks of (a) hospitalization for HF and (b) the combined endpoint of cardiovascular mortality and hospitalization for HF at 1 year, in patients with HF and preserved LVEF. However, they have no significant effect on mortality during more prolonged follow-up; the width of the 95% confidence limits is compatible with a benefit as big as 10% or a hazard as large as 13%.