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Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial.

Düngen HD, Apostolovic S, Inkrot S, Tahirovic E, Töpper A, Mehrhof F, Prettin C, Putnikovic B, Neskovic AN, Krotin M, Sakac D, Lainscak M, Edelmann F, Wachter R, Rau T, Eschenhagen T, Doehner W, Anker SD, Waagstein F, Herrmann-Lingen C, Gelbrich G, Dietz R, CIBIS-ELD investigators and Project Multicentre Trials in the Competence Network Heart Failu - Eur. J. Heart Fail. (2011)

Bottom Line: None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64).The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001).The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine-Cardiology, Charité-Universitätsmedizin, Competence Network Heart Failure, Campus Virchow-Klinkum, Berlin, Germany. hans-dirk.duengen@charite.de

ABSTRACT

Aims: Various beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure.

Methods and results: We performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5-3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001).

Conclusion: Overall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group. This study is registered with controlled-trials.com, number ISRCTN34827306.

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Predictors of tolerability. Filled diamonds indicate factors significantly related to outcome.
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HFR020F2: Predictors of tolerability. Filled diamonds indicate factors significantly related to outcome.

Mentions: None of the beta-blockers was superior with regards to tolerability according to the primary endpoint of reaching the respective target doses when following the recommended titration scheme (Table 2). This result remained the same when adjusting for treatment effect covariates (Figure 2). Kaplan–Meier estimates show that the percentage of patients reaching the ascending dose levels in line with the titration scheme did not differ between groups (Figure 3). Overall, 31% of patients reached the full, and 55% tolerated at least half of the target doses (Table 2). The mean daily dose reached at follow-up was 5.0 mg for bisoprolol and 23.9 mg for carvedilol in patients ≤85 kg (47.7 mg in patients >85 kg). Factors associated with reaching the primary endpoint are shown in Figure 2.Table 2


Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial.

Düngen HD, Apostolovic S, Inkrot S, Tahirovic E, Töpper A, Mehrhof F, Prettin C, Putnikovic B, Neskovic AN, Krotin M, Sakac D, Lainscak M, Edelmann F, Wachter R, Rau T, Eschenhagen T, Doehner W, Anker SD, Waagstein F, Herrmann-Lingen C, Gelbrich G, Dietz R, CIBIS-ELD investigators and Project Multicentre Trials in the Competence Network Heart Failu - Eur. J. Heart Fail. (2011)

Predictors of tolerability. Filled diamonds indicate factors significantly related to outcome.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3101867&req=5

HFR020F2: Predictors of tolerability. Filled diamonds indicate factors significantly related to outcome.
Mentions: None of the beta-blockers was superior with regards to tolerability according to the primary endpoint of reaching the respective target doses when following the recommended titration scheme (Table 2). This result remained the same when adjusting for treatment effect covariates (Figure 2). Kaplan–Meier estimates show that the percentage of patients reaching the ascending dose levels in line with the titration scheme did not differ between groups (Figure 3). Overall, 31% of patients reached the full, and 55% tolerated at least half of the target doses (Table 2). The mean daily dose reached at follow-up was 5.0 mg for bisoprolol and 23.9 mg for carvedilol in patients ≤85 kg (47.7 mg in patients >85 kg). Factors associated with reaching the primary endpoint are shown in Figure 2.Table 2

Bottom Line: None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64).The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001).The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine-Cardiology, Charité-Universitätsmedizin, Competence Network Heart Failure, Campus Virchow-Klinkum, Berlin, Germany. hans-dirk.duengen@charite.de

ABSTRACT

Aims: Various beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure.

Methods and results: We performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5-3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001).

Conclusion: Overall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group. This study is registered with controlled-trials.com, number ISRCTN34827306.

Show MeSH
Related in: MedlinePlus