Aliskiren, enalapril, or aliskiren and enalapril in heart failure

McMurray, J. J.V. et al. (2016) Aliskiren, enalapril, or aliskiren and enalapril in heart failure. New England Journal of Medicine, 374(16), pp. 1521-1532. (doi:10.1056/NEJMoa1514859) (PMID:27043774)

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Abstract

BACKGROUND Among patients with chronic heart failure, angiotensin-converting–enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODS After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTS After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P=0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P=0.009) and an elevated potassium level (17.1% vs. 12.5%, P<0.001). CONCLUSIONS In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapril

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Greenlaw, Miss Nicola and McMurray, Professor John
Authors: McMurray, J. J.V., Krum, H., Abraham, W. T., Dickstein, K., Køber, L. V., Desai, A. S., Solomon, S. D., Greenlaw, N., Ali, M. A., Chiang, Y., Shao, Q., Tarnesby, G., and Massie, B. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:New England Journal of Medicine
Publisher:Massachusetts Medical Society
ISSN:0028-4793
ISSN (Online):1533-4406
Published Online:04 April 2016
Copyright Holders:Copyright © 2016 Massachusetts Medical Society
First Published:First published in New England Journal of Medicine 374(16):1521-1532
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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