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Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial

Funck-Brentano, Christian; van Veldhuisen, Dirk J.; van de Ven, Louis L. M.; Follath, Ferenc; Goulder, Michael and Willenheimer, Ronnie LU (2011) In European Journal of Heart Failure 13(7). p.765-772
Abstract
Aims Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. Methods and results In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints... (More)
Aims Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. Methods and results In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at >= 50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P < 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P < 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. Conclusion The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adrenergic beta-antagonists/administration and dosage, Angiotensin-converting enzyme inhibitors/administration and dosage, Dose-response relationship, Drug, Heart failure/drug therapy, Risk, factors, Treatment outcome
in
European Journal of Heart Failure
volume
13
issue
7
pages
765 - 772
publisher
Elsevier
external identifiers
  • wos:000292373400012
  • scopus:79959978534
ISSN
1879-0844
DOI
10.1093/eurjhf/hfr051
language
English
LU publication?
yes
id
6c63b320-8516-47c0-87aa-20335045a184 (old id 2029071)
date added to LUP
2011-08-02 08:57:01
date last changed
2017-10-22 03:23:31
@article{6c63b320-8516-47c0-87aa-20335045a184,
  abstract     = {Aims Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. Methods and results In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at &gt;= 50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P &lt; 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P &lt; 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. Conclusion The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.},
  author       = {Funck-Brentano, Christian and van Veldhuisen, Dirk J. and van de Ven, Louis L. M. and Follath, Ferenc and Goulder, Michael and Willenheimer, Ronnie},
  issn         = {1879-0844},
  keyword      = {Adrenergic beta-antagonists/administration and dosage,Angiotensin-converting enzyme inhibitors/administration and dosage,Dose-response relationship,Drug,Heart failure/drug therapy,Risk,factors,Treatment outcome},
  language     = {eng},
  number       = {7},
  pages        = {765--772},
  publisher    = {Elsevier},
  series       = {European Journal of Heart Failure},
  title        = {Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: a post hoc analysis of the CIBIS-III trial},
  url          = {http://dx.doi.org/10.1093/eurjhf/hfr051},
  volume       = {13},
  year         = {2011},
}