{"id":"0ea045a913f8","type":"article","url":"https://hartvaat.nl/2016/04/21/aliskiren-enalapril-of-de-combinatie-bij-hartfalen-nejm-atmosphere-trial/","title":"Aliskiren, enalapril of de combinatie bij hartfalen: NEJM ATMOSPHERE-trial","title_en":"Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure.","category":"hartfalen","category_label":"Hartfalen","professions":["apotheker","cardioloog"],"tags":["acuut-hartfalen","bisoprolol","hfref","sacubitril-valsartan","step-hfpef"],"journal":"The New England journal of medicine","doi":"10.1056/NEJMoa1514859","source_url":"https://doi.org/10.1056/NEJMoa1514859","authors":["John J V McMurray","Henry Krum","William T Abraham","Kenneth Dickstein","Lars V Køber","Akshay S Desai","Scott D Solomon","Nicola Greenlaw","M Atif Ali","Yanntong Chiang","Qing Shao","Georgia Tarnesby","Barry M Massie"],"significance":8,"published":"2016-04-21","source_date":"2016-04-21","image":"","kennis":["https://hartvaat.nl/kennis/hartfalen/wat-is-hartfalen/","https://hartvaat.nl/kennis/hartfalen/hfref-hartfalen-met-verminderde-ejectie/"],"congress":"","summary_en":"This NEJM trial showed that aliskiren (a direct renin inhibitor) was neither superior nor noninferior to enalapril in HFrEF, and the combination increased adverse events without clinical benefit. The results effectively ended development of direct renin inhibition for heart failure.","created":"2026-07-03T10:26:04Z","updated":"2026-07-03T18:38:23Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"NEJM-trial die aliskiren (directe renineremmer) vergeleek met enalapril en de combinatie bij hartfalen met verminderde ejectiefractie. Definitieve trial die de rol van directe renineremming bij hartfalen onderzocht.","abstract_original":"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. (Funded by Novartis; ATMOSPHERE ClinicalTrials.gov number, NCT00853658.)."}