Declining risk of sudden death in heart failure

Li Shen, Pardeep S. Jhund, Mark C. Petrie, Brian L. Claggett, Simona Barlera, John G.F. Cleland, 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. ZileJohn J.V. McMurray

Research output: Contribution to journalArticle

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Abstract

BACKGROUND The 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. METHODS We 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. RESULTS Sudden 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. CONCLUSIONS Rates 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.

Original languageEnglish (US)
Pages (from-to)41-51
Number of pages11
JournalNew England Journal of Medicine
Volume377
Issue number1
DOIs
StatePublished - Jul 6 2017

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Sudden Death
Heart Failure
Random Allocation
Clinical Trials
Mineralocorticoid Receptor Antagonists
Implantable Defibrillators
Angiotensin Receptor Antagonists
Incidence
Proportional Hazards Models
Angiotensin-Converting Enzyme Inhibitors
Cause of Death

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Shen, L., Jhund, P. S., Petrie, M. C., Claggett, B. L., Barlera, S., Cleland, J. G. F., ... McMurray, J. J. V. (2017). Declining risk of sudden death in heart failure. New England Journal of Medicine, 377(1), 41-51. https://doi.org/10.1056/NEJMoa1609758

Declining risk of sudden death in heart failure. / Shen, Li; Jhund, Pardeep S.; Petrie, Mark C.; Claggett, Brian L.; Barlera, Simona; Cleland, John G.F.; Dargie, Henry J.; Granger, Christopher B.; Kjekshus, John; Køber, Lars; Latini, Roberto; Maggioni, Aldo P.; Packer, Milton; Pitt, Bertram; Solomon, Scott D.; Swedberg, Karl; Tavazzi, Luigi; Wikstrand, John; Zannad, Faiez; Zile, Michael R.; McMurray, John J.V.

In: New England Journal of Medicine, Vol. 377, No. 1, 06.07.2017, p. 41-51.

Research output: Contribution to journalArticle

Shen, L, Jhund, PS, Petrie, MC, Claggett, BL, Barlera, S, Cleland, JGF, Dargie, HJ, Granger, CB, Kjekshus, J, Køber, L, Latini, R, Maggioni, AP, Packer, M, Pitt, B, Solomon, SD, Swedberg, K, Tavazzi, L, Wikstrand, J, Zannad, F, Zile, MR & McMurray, JJV 2017, 'Declining risk of sudden death in heart failure', New England Journal of Medicine, vol. 377, no. 1, pp. 41-51. https://doi.org/10.1056/NEJMoa1609758
Shen L, Jhund PS, Petrie MC, Claggett BL, Barlera S, Cleland JGF et al. Declining risk of sudden death in heart failure. New England Journal of Medicine. 2017 Jul 6;377(1):41-51. https://doi.org/10.1056/NEJMoa1609758
Shen, Li ; Jhund, Pardeep S. ; Petrie, Mark C. ; Claggett, Brian L. ; Barlera, Simona ; Cleland, John G.F. ; Dargie, Henry J. ; Granger, Christopher B. ; Kjekshus, John ; Køber, Lars ; Latini, Roberto ; Maggioni, Aldo P. ; Packer, Milton ; Pitt, Bertram ; Solomon, Scott D. ; Swedberg, Karl ; Tavazzi, Luigi ; Wikstrand, John ; Zannad, Faiez ; Zile, Michael R. ; McMurray, John J.V. / Declining risk of sudden death in heart failure. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 1. pp. 41-51.
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AU - Jhund, Pardeep S.

AU - Petrie, Mark C.

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AU - Barlera, Simona

AU - Cleland, John G.F.

AU - Dargie, Henry J.

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AU - Latini, Roberto

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AU - Packer, Milton

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AU - Swedberg, Karl

AU - Tavazzi, Luigi

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AU - McMurray, John J.V.

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N2 - BACKGROUND The 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. METHODS We 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. RESULTS Sudden 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. CONCLUSIONS Rates 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.

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