Akshay S Desai1, John J V McMurray2, Milton Packer3, Karl Swedberg4, Jean L Rouleau5, Fabian Chen6, Jianjian Gong6, Adel R Rizkala6, Abdel Brahimi1, Brian Claggett1, Peter V Finn1, Loren Howard Hartley1, Jiankang Liu1, Martin Lefkowitz6, Victor Shi6, Michael R Zile7, Scott D Solomon8. 1. Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. 2. British Heart Foundation Cardiovascular Research Center, University of Glasgow, Glasgow, UK. 3. Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, USA. 4. Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden National Heart and Lung Institute, Imperial College, London, UK. 5. Institut de Cardiologie, Université de Montréal, Montreal, Canada. 6. Novartis Pharmaceuticals Corporation, East Hanover, USA. 7. Medical University of South Carolina and Ralph H. Johnston Veterans Administration Medical Center, Charleston, USA. 8. Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA ssolomon@rics.bwh.harvard.edu.
Abstract
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. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
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. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Muthiah Vaduganathan; Ravi B Patel; Robert J Mentz; Haris Subacius; Neal A Chatterjee; Stephen J Greene; Andrew P Ambrosy; Aldo P Maggioni; James E Udelson; Karl Swedberg; Marvin A Konstam; Christopher M O'Connor; Javed Butler; Mihai Gheorghiade; Faiez Zannad Journal: Am J Cardiol Date: 2018-04-11 Impact factor: 2.778
Authors: Brian G Reid; Matthew S Stratton; Samantha Bowers; Maria A Cavasin; Kimberley M Demos-Davies; Isidro Susano; Timothy A McKinsey Journal: J Mol Cell Cardiol Date: 2016-04-27 Impact factor: 5.000
Authors: Òscar Miró; Xavier Rossello; Elke Platz; Josep Masip; Danielle M Gualandro; W Frank Peacock; Susanna Price; Louise Cullen; Salvatore DiSomma; Mucio Tavares de Oliveira; John Jv McMurray; Francisco J Martín-Sánchez; Alan S Maisel; Christiaan Vrints; Martin R Cowie; Héctor Bueno; Alexandre Mebazaa; Christian Mueller Journal: Eur Heart J Acute Cardiovasc Care Date: 2020-08