Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril, Compared to the Opposite Order: Results of the Randomized CIBIS III Trial

Henry Krum, Dirk J. Van Veldhuisen, Christian Funck-Brentano, Emilio Vanoli, Bernard Silke, Erland Erdmann, Ferenc Follath, Piotr Ponikowski, Michael Goulder, Wilfried Meyer, Philippe Lechat, Ronnie Willenheimer

Research output: Contribution to journalArticle

Abstract

Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. Methods: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. Results: During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events. Conclusion: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.

Original languageEnglish
Pages (from-to)89-98
Number of pages10
JournalCardiovascular Therapeutics
Volume29
Issue number2
DOIs
Publication statusPublished - Apr 2011

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Bisoprolol
Enalapril
Sudden Death
Heart Failure
Confidence Intervals
Therapeutics
Systolic Heart Failure
Angiotensin Receptor Antagonists
Stroke Volume

Keywords

  • Adrenergic β-antagonists
  • Angiotensin-converting enzyme inhibitors
  • Drugs
  • Heart failure
  • Sudden death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)
  • Pharmacology
  • Medicine(all)

Cite this

Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril, Compared to the Opposite Order : Results of the Randomized CIBIS III Trial. / Krum, Henry; Van Veldhuisen, Dirk J.; Funck-Brentano, Christian; Vanoli, Emilio; Silke, Bernard; Erdmann, Erland; Follath, Ferenc; Ponikowski, Piotr; Goulder, Michael; Meyer, Wilfried; Lechat, Philippe; Willenheimer, Ronnie.

In: Cardiovascular Therapeutics, Vol. 29, No. 2, 04.2011, p. 89-98.

Research output: Contribution to journalArticle

Krum, H, Van Veldhuisen, DJ, Funck-Brentano, C, Vanoli, E, Silke, B, Erdmann, E, Follath, F, Ponikowski, P, Goulder, M, Meyer, W, Lechat, P & Willenheimer, R 2011, 'Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril, Compared to the Opposite Order: Results of the Randomized CIBIS III Trial', Cardiovascular Therapeutics, vol. 29, no. 2, pp. 89-98. https://doi.org/10.1111/j.1755-5922.2010.00185.x
Krum, Henry ; Van Veldhuisen, Dirk J. ; Funck-Brentano, Christian ; Vanoli, Emilio ; Silke, Bernard ; Erdmann, Erland ; Follath, Ferenc ; Ponikowski, Piotr ; Goulder, Michael ; Meyer, Wilfried ; Lechat, Philippe ; Willenheimer, Ronnie. / Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril, Compared to the Opposite Order : Results of the Randomized CIBIS III Trial. In: Cardiovascular Therapeutics. 2011 ; Vol. 29, No. 2. pp. 89-98.
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abstract = "Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. Methods: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35{\%}, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. Results: During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95{\%} confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95{\%} CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95{\%} CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95{\%} CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95{\%} CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95{\%} CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events. Conclusion: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.",
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T1 - Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril, Compared to the Opposite Order

T2 - Results of the Randomized CIBIS III Trial

AU - Krum, Henry

AU - Van Veldhuisen, Dirk J.

AU - Funck-Brentano, Christian

AU - Vanoli, Emilio

AU - Silke, Bernard

AU - Erdmann, Erland

AU - Follath, Ferenc

AU - Ponikowski, Piotr

AU - Goulder, Michael

AU - Meyer, Wilfried

AU - Lechat, Philippe

AU - Willenheimer, Ronnie

PY - 2011/4

Y1 - 2011/4

N2 - Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. Methods: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. Results: During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events. Conclusion: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.

AB - Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. β-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. Methods: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction ≤35%, without ACEI, β-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. Results: During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P= 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P= 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P= 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P= 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P= 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P= 0.053. There were no significant between-group differences in any other fatal events. Conclusion: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.

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KW - Angiotensin-converting enzyme inhibitors

KW - Drugs

KW - Heart failure

KW - Sudden death

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