Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure.

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. (Funded by Novartis; ATMOSPHERE ClinicalTrials.gov number, NCT00853658.).

• 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, ATMOSPHERE Committees Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 374 Issue 16 Pg. 1521-32 (Apr 21 2016) ISSN: 1533-4406 [Electronic] United States
• PMID: 27043774 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Angiotensin-Converting Enzyme Inhibitors
• Fumarates
• aliskiren
• Enalapril
• Renin

Topics

• Aged
• Amides (adverse effects, therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (adverse effects, therapeutic use)
• Chronic Disease
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Double-Blind Method
• Drug Therapy, Combination
• Enalapril (adverse effects, therapeutic use)
• Female
• Follow-Up Studies
• Fumarates (adverse effects, therapeutic use)
• Heart Failure (complications, drug therapy)
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Renin (antagonists & inhibitors)
• Stroke Volume
• Treatment Failure