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.
- heart failure
- preserved ejection fraction
- mid-range ejection fraction
- diastolic dysfunction
- systematic review
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Contributors SLZ initiated the project, designed the search strategy, undertook the search, extracted data and assessed risk of bias, analysed the data and drafted the manuscript. FTC undertook the search, extracted data and assessed risk of bias and edited the manuscript. AAN assisted with assessment of trials for inclusion and edited the manuscript. AMS provided guidance on interpretation of results, critically advising important intellectual content and involved in editing the final manuscript. TM provided guidance on interpretation of results and involved in editing the final manuscript. DOO provided guidance on interpretation of results, critically advising important intellectual content and involved in editing the final manuscript. SA provided statistical guidance, advice on search strategy, undertook statistical analysis and edited the manuscript. All authors approve of the final version to be published. and are accountable to all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding Open access for this article was funded by King’s College London. This work was supported in part by the British Heart Foundation (BHF). Dr Ayis was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas' NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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