Heart Rate and Cardiac Rhythm Relationships With Bisoprolol Benefit in Chronic Heart Failure in CIBIS II Trial

Abstract

on behalf of the CIBIS II InvestigatorsBackground-␤-Blockade-induced benefit in heart failure (HF) could be related to baseline heart rate and treatmentinduced heart rate reduction, but no such relationships have been demonstrated. Methods and Results-In CIBIS II, we studied the relationships between baseline heart rate (BHR), heart rate changes at 2 months (HRC), nature of cardiac rhythm (sinus rhythm or atrial fibrillation), and outcomes (mortality and hospitalization for HF). Multivariate analysis of CIBIS II showed that in addition to ␤-blocker treatment, BHR and HRC were both significantly related to survival and hospitalization for worsening HF, the lowest BHR and the greatest HRC being associated with best survival and reduction of hospital admissions. No interaction between the 3 variables was observed, meaning that on one hand, HRC-related improvement in survival was similar at all levels of BHR, and on the other hand, bisoprolol-induced benefit over placebo for survival was observed to a similar extent at any level of both BHR and HRC. Bisoprolol reduced mortality in patients with sinus rhythm (relative risk 0.58, PϽ0.001) but not in patients with atrial fibrillation (relative risk 1.16, PϭNS). A similar result was observed for cardiovascular mortality and hospitalization for HF worsening. Conclusions-BHR and HRC are significantly related to prognosis in heart failure. ␤-Blockade with bisoprolol further improves survival at any level of BHR and HRC and to a similar extent. The benefit of bisoprolol is questionable, however, in patients with atrial fibrillation.

Beta-Blocker Use and Risk of Symptomatic Bradyarrhythmias: A Hospital-Based Case-Control Study

“…The evidence from RCTs indicates that β-blockers can be used safely and successfully in most elderly patients with CHF. [5,12,25] Further evidence comes from the SENIORS trial which was specifically designed to investigate the effects of beta-blockade (Nebivolol) in elderly CHF patients (mean age 76 years). [7] Bradycardia was reported as an adverse event in 118/1067 (11%) patients in β-blockers arm versus 28/1061 (2.6%) patients in placebo arm.…”

“…[5,6,9,10] These results should alleviate concerns in prescribing β-blockers particularly in patients with heart failure where the absolute survival benefits of β-blockers are most pronounced. [11,25] However, medication could be a double-edge sword.…”

“…[1][2][3] Overall, the benefit gained from the use of β-blockers outweighs the potential side effect. Metoprolol, bisoprolol, carvedilol and nebivolol have been proven in reducing morbidity and mortality in heart failure, [4][5][6][7] and reported to be well tolerated in these clinical trials. [1,5,6,[8][9][10][11] Most of the available information on the incidence of bradycardia caused by β-blockers comes from heart failure randomized controlled trials (RCTs).…”

“…Metoprolol, bisoprolol, carvedilol and nebivolol have been proven in reducing morbidity and mortality in heart failure, [4][5][6][7] and reported to be well tolerated in these clinical trials. [1,5,6,[8][9][10][11] Most of the available information on the incidence of bradycardia caused by β-blockers comes from heart failure randomized controlled trials (RCTs). A review article on different types of β-blockers in heart failure trials found that the incidence of bradycardia was higher among patients on β-blockers (0.4%-12%) as compared to placebo (0-5%).…”

Benefits and Risks of Long-term Amiodarone Therapy for Persistent Atrial Fibrillation: A Meta-analysis

“…One hypothesis suggests that amiodarone can induce atrioventricular delay, especially in patients with severe left ventricular failure (ejection fraction <30%). 33,34 Dronedarone, a new derivative of amiodarone, was reported to be associated with an increase in mortality in patients with chronic heart failure. 15,16,35 Our results showed that the mortality rate in those who received long-term amiodarone therapy was low (4.7 per 100 patient-years).…”