Results from post-hoc analyses of the CIBIS II trial: effect of bisoprolol in high-risk patient groups with chronic heart failure.

BACKGROUND: The beneficial effects of the beta-blocker bisoprolol on mortality and rate of hospitalisation as well as its safety in patients with chronic heart failure has been proven. However, its efficacy in patients in whom beta-blockers have traditionally been contraindicated or caution has been advised has not been clearly determined. Therefore, analyses in high-risk subgroups of patients taking part in CIBIS II have been performed to investigate the effect of bisoprolol in elderly patients, in patients with type 2 diabetes, with renal failure, NYHA functional class IV or concomitantly treated with digitalis, aldosterone antagonists or amiodarone. METHODS: High-risk subgroups of patients with chronic heart failure taking part in the CIBIS II study were retrospectively analysed with respect to mortality, hospitalisation, combined endpoint of cardiovascular mortality or hospitalisation for cardiovascular reasons and treatment withdrawal as well as cause of death and hospitalisation. Analysis is based on intention-to-treat. RESULTS: It was demonstrated that in spite of the expected increase in the overall risk of death and hospitalisation, patients who are diabetic, have renal impairment, NYHA class IV symptoms, are elderly, are taking either digitalis, amiodarone or aldosterone antagonists as co-medication benefit equally from beta-blockade with bisoprolol as patients without these complications or drugs. Benefit was shown for the primary endpoint all cause mortality, as well as for the secondary endpoints. CONCLUSIONS: Contrary to the hitherto prevailing doctrine of not using beta-blockers in high risk patient groups with chronic heart failure, retrospective analyses of the CIBIS II study justify the use of this drug class in patients regardless of age, NYHA functional class, the presence of diabetes, renal impairment or concomitant treatment with digitalis, amiodarone or aldosterone antagonists.

Bisoprolol pilot studies in myocardial infarction.

The efficacy of beta-blockade after myocardial infarction (MI) has been investigated in a series of studies. When beta-blockers are used during the first hours after the onset of MI, a reduction in infarct size, mortality, and nonfatal reinfarction may occur. Bisoprolol is a highly beta1-selective beta-blocker, without intrinsic sympathomimetic activity (ISA), and with a plasma elimination half-life of 10-12 h, permitting treatment with one daily dose. Because no experience with bisoprolol was available in MI, its safety and efficacy were studied in two open, uncontrolled pilot studies. The first study was a dose-finding study in 37 patients with a 3-day-old MI. Bisoprolol was given intravenously and carefully titrated in steps of 1 mg up to a cumulative maximum dose of 5 mg. Subsequently, the patients received 10 mg of oral bisoprolol once daily (o.d.) until the end of the study. Based on the results of this first pilot study, a second pilot study was performed in which bisoprolol was given within the first 6 h after the onset of MI. Intravenous (i.v.) bisoprolol was titrated in two steps of 2.5 mg each, directly followed by 10 mg of oral bisoprolol o.d. The aim of this study was to investigate the influence of i.v. and subsequent oral bisoprolol on central hemodynamics. The results of these studies demonstrate that i.v. and subsequent oral administration of bisoprolol is well tolerated and indicate that the selected dose regimen is hemodynamically safe.