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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 and Meyer, Wilfried, et al. (2011) In Cardiovascular Therapeutics 29(2). p.89-98
Abstract
P>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. beta-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, beta-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... (More)
P>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. beta-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, beta-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. (Less)
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Contribution to journal
publication status
published
subject
keywords
Adrenergic beta-antagonists, Angiotensin-converting enzyme inhibitors, Drugs, Heart failure, Sudden death
in
Cardiovascular Therapeutics
volume
29
issue
2
pages
89 - 98
publisher
Wiley-Blackwell
external identifiers
  • wos:000287740100001
  • scopus:79952014101
ISSN
1755-5914
DOI
10.1111/j.1755-5922.2010.00185.x
language
English
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yes
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ca2e4382-ea6e-4491-a41b-a9734ff76a34 (old id 1869953)
date added to LUP
2011-04-04 08:33:31
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2017-06-04 03:13:15
@article{ca2e4382-ea6e-4491-a41b-a9734ff76a34,
  abstract     = {P&gt;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. beta-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 &lt; 35%, without ACEI, beta-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.},
  author       = {Krum, Henry and van Veldhuisen, Dirk J. and Funck-Brentano, Christian and Vanoli, Emilio and Silke, Bernard and Erdmann, Erland and Follath, Ferenc and Ponikowski, Piotr and Goulder, Michael and Meyer, Wilfried and Lechat, Philippe and Willenheimer, Ronnie},
  issn         = {1755-5914},
  keyword      = {Adrenergic beta-antagonists,Angiotensin-converting enzyme inhibitors,Drugs,Heart failure,Sudden death},
  language     = {eng},
  number       = {2},
  pages        = {89--98},
  publisher    = {Wiley-Blackwell},
  series       = {Cardiovascular Therapeutics},
  title        = {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},
  url          = {http://dx.doi.org/10.1111/j.1755-5922.2010.00185.x},
  volume       = {29},
  year         = {2011},
}