• Li Shen, Pardeep S Jhund, Mark C Petrie, Brian L Claggett, Simona Barlera, ClelandJohn G FJGFFrom the British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences (L.S., P.S.J., M.C.P., J.J.V.M.), and Robertson Centre for Biostatistics and Clinical Trials, Institute of Health , Henry J Dargie, Christopher B Granger, John Kjekshus, Lars Køber, Roberto Latini, Aldo P Maggioni, Milton Packer, Bertram Pitt, Scott D Solomon, Karl Swedberg, Luigi Tavazzi, John Wikstrand, Faiez Zannad, Michael R Zile, and McMurrayJohn J VJJVFrom the British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences (L.S., P.S.J., M.C.P., J.J.V.M.), and Robertson Centre for Biostatistics and Clinical Trials, Institute of Health.
• From the British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences (L.S., P.S.J., M.C.P., J.J.V.M.), and Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing (J.G.F.C.), University of Glasgow, the Department of Cardiology, Golden Jubilee National Hospital (M.C.P.), and the Cardiology Department, Glasgow Royal Infirmary (H.J.D.), Glasgow, and the National Heart and Lung Institute, Imperial College London, London (J.G.F.C.) - all in the United Kingdom; the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (B.L.C., S.D.S.); the Department of Cardiovascular Research, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Milan (S.B., R.L.), Associazione Nazionale Medici Cardiologi Ospedalieri Research Center, Florence (A.P.M.), and Maria Cecilia Hospital, Gruppo Villa Maria Care and Research, Ettore Sansavini Health Science Foundation, Cotignola (L.T.) - all in Italy; Duke Clinical Research Institute, Duke University, Durham, NC (C.B.G.); Rikshospitalet University Hospital, Oslo (J.K.); the Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen (L.K.); Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas (M.P.); the Department of Medicine, University of Michigan, Ann Arbor (B.P.); the Center for Person-Centered Care (K.S.) and Sahlgrenska Academy (J.W.), University of Gothenburg, Gothenburg, Sweden; INSERM Centre d'Investigation Clinique 1433, Université de Lorraine and Centre Hospitalier Universitaire, Nancy, France (F.Z.); and the Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston (M.R.Z.).
• N. Engl. J. Med. 2017 Jul 6; 377 (1): 41-51.

BackgroundThe risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail.MethodsWe analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization.ResultsSudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P=0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis.ConclusionsRates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.).

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