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Meta-Analysis
. 2017 Nov;4(4):402-408.
doi: 10.1002/ehf2.12204. Epub 2017 Sep 4.

Renin-angiotensin blockade in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Muhammad Shahzeb Khan  1 , Gregg C Fonarow  2 , Hassan Khan  3 , Stephen J Greene  4 , Stefan D Anker  5 , Mihai Gheorghiade  6 , Javed Butler  7
Affiliations
Meta-Analysis

Renin-angiotensin blockade in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Muhammad Shahzeb Khan et al. ESC Heart Fail. 2017 Nov.

Abstract

Studies with angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) in patients with heart failure with preserved ejection fraction (HFpEF) have yielded inconsistent results. To conduct a systematic review and meta-analysis of all evidence for ACE-I and ARBs in patients with HFpEF, we searched PubMed, Ovid SP, Embase, and Cochrane database to identify randomized trials and observational studies that compared ACE-I or ARBs against placebo or standard therapy in HFpEF patients. Random-effect models were used to pool the data, and I2 testing was performed to assess the heterogeneity of the included studies. A total of 13 studies (treatment arm = 8676 and control arm = 8608) were analysed. Pooled analysis of randomized trials for ACE-I and ARBs (n = 6) did not show any effect on all-cause mortality [relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.93-1.11, P = 0.68, I2 = 0%], while results from observational studies showed a significant improvement (RR = 0.91, 95% CI = 0.87-0.95, P = 0.005, I2 = 81.5%). In pooled analyses of all studies, ACE-I showed a reduction of all-cause mortality (RR = 0.91, 95% CI = 0.87-0.95, P = 0.01). There was no reduction in cardiovascular mortality seen, but in pooled analysis of randomized trials, there was a trend towards reduced HF hospitalization risk (RR = 0.91, 95% CI = 0.83-1.01, I2 = 0%, P = 0.074). These data suggest that ACE-I and ARBs may have a role in improving outcomes of patients with HFpEF, underscoring the need for future research with careful patient selection, and trial design and conduct.

Keywords: Angiotensin receptor blockers; Angiotensin-converting enzyme inhibitors; Heart failure; Preserved ejection fraction; Renin-angiotensin system.

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Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram showing detailed search strategy.
Figure 2
Figure 2
Funnel plot representing publication bias for all‐cause mortality.
Figure 3
Figure 3
(A) Effect of angiotensin‐converting enzyme inhibitors (ACE‐Is) and angiotensin receptor blockers (RCBs) on all‐cause mortality in patients with heart failure with preserved ejection fraction. (B) Effect of ACE‐Is on all‐cause mortality in patients with heart failure with preserved ejection fraction. CI, confidence interval; RCT, randomized clinical trial; RR, relative risk.
Figure 4
Figure 4
Effect of angiotensin‐converting enzyme inhibitors (ACE‐Is) and angiotensin receptor blockers (RCBs) on cardiovascular mortality in patients with heart failure with preserved ejection fraction. CI, confidence interval; RCT, randomized clinical trial; RR, relative risk.
Figure 5
Figure 5
(A) Effect of angiotensin‐converting enzyme inhibitors (ACE‐Is) and angiotensin receptor blockers (RCBs) on hospitalizations due to heart failure in patients with heart failure with preserved ejection fraction. (B) Effect of ACE‐I and RCBs on hospitalizations or mortality in patients with heart failure with preserved ejection fraction. CI, confidence interval; RCT, randomized clinical trial; RR, relative risk.
See this image and copyright information in PMC

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