Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial

Scott D. Solomon, Brian Claggett, Akshay S. Desai, Milton Packer, Michael Zile, Karl Swedberg, Jean L. Rouleau, Victor C. Shi, Randall C. Starling, Ömer Kozan, Andrej Dukat, Martin P. Lefkowitz, John J V McMurray

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Background-The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and mortality compared with enalapril in patients with heart failure (HF) and reduced ejection fraction (EF) in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We evaluated the influence of EF on clinical outcomes and on the effectiveness of sacubitril/valsartan compared with enalapril. Methods and Results-Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV HF with reduced EF [left ventricular EF (LVEF) ≤40%] were randomized to sacubitril/valsartan 97/103 mg twice daily versus enalapril 10 mg twice daily and followed for a median of 27 months. The primary study end point was cardiovascular death or HF hospitalization. LVEF was assessed at the sites and recorded on case report forms. We related LVEF to study outcomes and assessed the effectiveness of sacubitril/valsartan across the LVEF spectrum. The mean LVEF in PARADIGM-HF, reported by sites, was 29.5 (interquartile range, 25-34). The risk of all outcomes increased with decreasing LVEF. Each 5-point reduction in LVEF was associated with a 9% increased risk of cardiovascular death or HF hospitalization (hazard ratio, 1.09; 95% confidence interval, 1.05-1.13; P

Original languageEnglish (US)
Article numbere002744
JournalCirculation: Heart Failure
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

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Keywords

  • heart
  • heart failure
  • humans
  • mineralocorticoid receptor antagonists
  • neprilysin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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