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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.). [ABSTRACT FROM AUTHOR]

The article reports on a trial on using angiotensin receptor-neprilysin inhibitor LCZ696 (L) with enalapril (E) in heart-failure patients with a reduced ejection fraction in 2014. Based on results, L, like E, reduced hospitalization risk by 21% and lessened heart failure symptoms and physical limitation, with the Lgroup having more patients with hypotension and less patients with renal impairment than the E group. L was found to be superior to E in reducing death and hospitalization risks.

The author reflects on the disruption of the heart-failure treatment algorithm by the drug LCZ696, a dual angiotensin II receptor and neprilysin inhibitor, as of 2014. She notes that it significantly reduced death rates of cardiovascular cases and hospitalization rates for heart failure patients with a reduced ejection fraction, and that patients were likely to withdraw from enalapril than from LCZ696. The author states that the PARADIGM-HF trial may be the new hope of heart failure patients.

A letter to the editor is presented in response to the article "Aliskiren, enalapril, or aliskiren and enalapril in heart failure" by John J. V. McMurray, and colleagues in the April 21, 2016 issue.

A response from the authors of the article "Angiotensin-neprilysin inhibition versus enalapril in heart failure" in the September 11, 2014 issue is presented.

A letter to the editor is presented in response to the article "Angiotensin-neprilysin inhibition versus enalapril in heart failure" by J. J. McMurray and colleagues in the September 11, 2014 issue.

A letter to the editor is presented in response to the article "Angiotensin-neprilysin inhibition versus enalapril in heart failure" by J. J. McMurray and colleagues in the September 11, 2014 issue.

A letter to the editor is presented in response to the article "Angiotensin-neprilysin inhibition versus enalapril in heart failure" by J. J. McMurray and colleagues in the September 11, 2014 issue.

A letter to the editor on patients with type 2 diabetes and hypertension is presented.