Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Abstract

Background: Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality.

Methods: We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO₂ max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI.

Results: We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo.

Conclusion: The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group.

Keywords: diastolic dysfunction; heart failure; meta-analysis; mid-range ejection fraction; preserved ejection fraction; systematic review.

Figure 1

Study flow diagram of the trial selection process. LVEF, left ventricular ejection fraction.

Figure 2

Pooled and individual estimates of relative risk (RR) and 95% CI of the primary outcome all-cause mortality for different therapies. Data are shown stratified by individual drug classes (beta-blockers, ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists and other drug classes). Random-effects model used.

Figure 3

Pooled and individual estimates of relative risk (RR) and 95% CIs of the secondary outcome cardiovascular mortality for different therapies. Data are shown stratified by individual class blockers (beta-blockers, ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists and other drug classes). Random-effects model used.

Figure 4

Pooled and individual estimates of relative risk (RR) and 95% CI of the secondary outcome heart failure hospitalisation for different therapies. Data are shown stratified by individual class blockers (beta-blockers, ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists and other drug classes). Random-effects model used.