TY - JOUR
T1 - Effect of the angiotensin-receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients
AU - Desai, Akshay S.
AU - McMurray, John J V
AU - Packer, Milton
AU - Swedberg, Karl
AU - Rouleau, Jean L.
AU - Chen, Fabian
AU - Gong, Jianjian
AU - Rizkala, Adel R.
AU - Brahimi, Abdel
AU - Claggett, Brian
AU - Finn, Peter V.
AU - Hartley, Loren Howard
AU - Liu, Jiankang
AU - Lefkowitz, Martin
AU - Shi, Victor
AU - Zile, Michael R.
AU - Solomon, Scott D.
N1 - Publisher Copyright:
© The Author 2015. Published on behalf of the European Society of Cardiology. All rights reserved.
PY - 2015/8/7
Y1 - 2015/8/7
N2 - Aims: The angiotensin-receptor-neprilysin inhibitor (ARNI) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospective comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. To more completely understand the components of this mortality benefit, we examined the effect of LCZ696 on mode of death. Methods and results: PARADIGM-HF was a prospective, double-blind, randomized trial in 8399 patients with chronic heart failure, New York Heart Association Class II-IV symptoms, and left ventricular ejection fraction ≤40% receiving guideline-recommended medical therapy and followed for a median of 27 months. Mode of death was adjudicated by a blinded clinical endpoints committee. The majority of deaths were cardiovascular (80.9%), and the risk of cardiovascular death was significantly reduced by treatment with LCZ (hazard ratio, HR 0.80, 95% CI 0.72-0.89, P < 0.001). Among cardiovascular deaths, both sudden cardiac death (HR 0.80, 95% CI 0.68-0.94, P = 0.008) and death due to worsening heart failure (HR 0.79, 95% CI 0.64-0.98, P = 0.034) were reduced by treatment with LCZ696 compared with enalapril. Deaths attributed to other cardiovascular causes, including myocardial infarction and stroke, were infrequent and distributed evenly between treatment groups, as were non-cardiovascular deaths. Conclusions: LCZ696 was superior to enalapril in reducing both sudden cardiac deaths and deaths from worsening heart failure, which accounted for the majority of cardiovascular deaths. Clinical Trial Registration: https://clinicaltrials.gov/, NCT01035255.
AB - Aims: The angiotensin-receptor-neprilysin inhibitor (ARNI) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospective comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. To more completely understand the components of this mortality benefit, we examined the effect of LCZ696 on mode of death. Methods and results: PARADIGM-HF was a prospective, double-blind, randomized trial in 8399 patients with chronic heart failure, New York Heart Association Class II-IV symptoms, and left ventricular ejection fraction ≤40% receiving guideline-recommended medical therapy and followed for a median of 27 months. Mode of death was adjudicated by a blinded clinical endpoints committee. The majority of deaths were cardiovascular (80.9%), and the risk of cardiovascular death was significantly reduced by treatment with LCZ (hazard ratio, HR 0.80, 95% CI 0.72-0.89, P < 0.001). Among cardiovascular deaths, both sudden cardiac death (HR 0.80, 95% CI 0.68-0.94, P = 0.008) and death due to worsening heart failure (HR 0.79, 95% CI 0.64-0.98, P = 0.034) were reduced by treatment with LCZ696 compared with enalapril. Deaths attributed to other cardiovascular causes, including myocardial infarction and stroke, were infrequent and distributed evenly between treatment groups, as were non-cardiovascular deaths. Conclusions: LCZ696 was superior to enalapril in reducing both sudden cardiac deaths and deaths from worsening heart failure, which accounted for the majority of cardiovascular deaths. Clinical Trial Registration: https://clinicaltrials.gov/, NCT01035255.
KW - Angiotensin-receptor blocker
KW - Clinical trial
KW - Heart failure
KW - Mortality
KW - Neprilysin inhibition
KW - Pharmacotherapy
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U2 - 10.1093/eurheartj/ehv186
DO - 10.1093/eurheartj/ehv186
M3 - Article
C2 - 26022006
AN - SCOPUS:84939603387
SN - 0195-668X
VL - 36
SP - 1990
EP - 1997
JO - European heart journal
JF - European heart journal
IS - 30
ER -