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

• Authors: Muhammad Shahzeb Khan, Hospital of Cook County; Gregg C. Fonarow, University of California Los Angeles; Hassan Khan, Emory University; Stephen J. Greene, Duke University; Stefan D. Anker, University Medical Center Göttingen; Mihai Gheorghiade, Northwestern University; Javed Butler, Emory University
• Journal Title: ESC Heart Failure
• Volume: Volume 4, Number 4
• Publisher: Wiley Periodicals Inc. | 2017-11-01, Pages 402-408
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1002/ehf2.12204
• Subjects: Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; Heart failure; Preserved ejection fraction; Angiotensin-converting enzyme inhibitors; Angiotensin receptor blockers; Renin-angiotensin system; CONVERTING ENZYME-INHIBITORS; SYSTOLIC FUNCTION; OLDER PATIENTS; DOUBLE-BLIND; TRIAL; IRBESARTAN; OUTCOMES; ANTAGONISTS; MORTALITY; QUALITY

Abstract

ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. 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.