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AimsVarious 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 resultsWe 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).ConclusionOverall 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.

A Randomised, Double-Blind Multicentre Study [CIBIS-ELD]; ISRCTN34827306).

This is the first large scale head to head beta-blockers trial in an elderly population with CHF. Besides determining which of two standard beta-blockers is best tolerated in elderly patients with systolic or diastolic CHF, we expect to gain further insight into the treatment of the particular population of patients with diastolic CHF.

AimsBeta-blockers (BBs) improve outcomes in heart failure. Results from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial previously demonstrated the feasibility of heart rate, not maximum dose, as a treatment goal. In this pre-specified analysis, we investigated the prognostic value of achieved heart rate after BB optimization on long-term mortality. Methods and resultsElderly heart failure patients from the CIBIS-ELD trial were invited to participate in a follow-up examination 4 years after the initial 12-week BB up-titration period. The relationship between all-cause mortality, BB dose, and heart rate after titration and potentially confounding clinical variables was analysed by multivariable Cox regression. In total, 728 patients (38% women; mean age 72.9 ± 5.4 years) were included. During a mean follow-up period of 45 ± 9 months, 134 patients (19%) died, thus accumulating 2268 patient-years at risk. There was no significant difference in baseline heart rate for survivors and non-survivors (P = 0.19). In models adjusting for age, sex, BB pre-treatment, ventricular function, heart rate, and NYHA class at baseline, a heart rate increase by 10 b.p.m. following up-titration was associated with a subsequent mortality hazard ratio of 1.19 (95% confidence interval 1.02-1.38, P = 0.023). The heart rate range with the lowest mortality and the fewest treatment-related adverse events was 55-64 b.p.m. The achieved BB dose was not associated with mortality risk.