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

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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; Willenheimer, Ronnie.

In: European Journal of Heart Failure, Vol. 13, No. 7, 2011, p. 765-772.

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Funck-Brentano, Christian ; van Veldhuisen, Dirk J. ; van de Ven, Louis L. M. ; Follath, Ferenc ; Goulder, Michael ; Willenheimer, Ronnie. / 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. In: European Journal of Heart Failure. 2011 ; Vol. 13, No. 7. pp. 765-772.

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TY - JOUR

T1 - 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

AU - Funck-Brentano, Christian

AU - van Veldhuisen, Dirk J.

AU - van de Ven, Louis L. M.

AU - Follath, Ferenc

AU - Goulder, Michael

AU - Willenheimer, Ronnie

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Adrenergic beta-antagonists/administration and dosage

KW - Angiotensin-converting enzyme inhibitors/administration and dosage

KW - Dose-response relationship

KW - Drug

KW - Heart failure/drug therapy

KW - Risk

KW - factors

KW - Treatment outcome

U2 - 10.1093/eurjhf/hfr051

DO - 10.1093/eurjhf/hfr051

M3 - Article

C2 - 21551161

VL - 13

SP - 765

EP - 772

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

SN - 1879-0844

IS - 7

ER -