The angiotensin receptor-neprilysin inhibitor LCZ696 was superior to enalapril in reducing the risk of death and of hospitalization for heart failure, according to results from the PARADIGM-HF Trial presented Aug. 30 as part of ESC Congress 2014 and simultaneously published in the New England Journal of Medicine.

Additional Resources ESC Congress 2014 Meeting Coverage Clinical Trial Summary FITs on the GO Video Interview Alfred Bove, MD, PhD, MACC

The study randomly assigned 8,442 patients with class II, III or IV heart failure and an ejection fraction of 40 percent or less to either LCZ696 or enalapril, in addition to recommended therapy. According to study investigators, the primary outcome was a composite of death from cardiovascular causes or hospitalization for trial. However, they also noted that the trial was also designed to detect a difference in the rates of death from cardiovascular causes.

The trial was stopped early after 27 months because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time it stopped, the primary outcome had occurred in 21.8 percent of patients in the LCZ696 group and 26.5 percent in the enalapril group. Fewer overall deaths occurred in patients receiving LCZ696 (17 percent) compared to enalapril (19.8 percent), and, according to study investigators, of these deaths 13.3 percent (LCZ696) and 16.5 percent (enalapril) died from cardiovascular-related causes. LCZ696 also reduced the risk of hospitalization for heart failure by 21 percent and decreased the symptoms and physical limitations of heart failure.

"The magnitude of these advantages of LCZ696 over ACE inhibition was highly significant and clinically important, particularly since the drug was compared with a dose of enalapril that has been shown to reduce mortality, as compared with placebo," the investigators said. They noted their findings provide "strong evidence" that combined inhibition of the angiotensin receptor and neprilysin in chronic heart failure patients is superior to inhibition of the renin-angiotensin system alone.

"PARADIGM-HF may well represent a new threshold of hope for patients with heart failure," writes Mariell Jessup, MD, FACC, in an accompanying editorial comment. "The beneficial results seen in PARADIGM-HF may apply to a wide spectrum of patients, even those who are currently receiving the best possible therapy."

Keywords: Enalapril, Receptors, Angiotensin, Heart Failure, Renin-Angiotensin System, Neprilysin, Tetrazoles

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