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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 discusses utilization of implantable cardioverter-defibrillators (ICDs) in management of heart failure. Topics discussed include reduction in premature death by ICDs usage in ventricular systolic dysfunction, involvement of nonischemic cardiomyopathy in patients, usage of angiotensin-converting- enzyme inhibitors along with mineralocorticoid-receptor, description of cardiac-resynchronization therapy for treatment process and implications for reduction in cardiac disease mortality.

The author discusses the lessons learned from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial in the U.S. Topics covered include the reduced potential benefits of spironolactone therapy for heart failure patients and the importance of natriuretic peptide levels as a predictor of adverse outcomes in heart failure patients particularly for those with preserved ejection fraction.

A response by John J. V. McMurray to a letter to the editor about his article "Systolic Heart Failure," in the January 21, 2010 issue is presented.

The article argues over the comment that lack of effect on cardiovascular mortality in GALACTIC-HF is due to an unfavorable effect of omecamtiv mecarbil on myocardial energetics, citing work in a model of acute ischemia in pigs and in whole hearts subjected to cardioplegia. Topics include deficiencies in the experimental approach undermine the conclusions contradictory to the lack of effect of omecamtiv mecarbil; and myocardial oxygen consumption and its inhibition of the resting myosin ATPase.

The article presents the views of the authors related to dapagliflozin reducing levels of serum urate seems the mechanism proposed by Borghi and Cicero explaining the benefits of dapagliflozin.

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.