Bisoprolol or enalapril followed by their combination for patients with congestive heart failure (CHF) and left ventricular ejection fraction (LVEF) ≤ 35%
Topic: Beta-blockers in heart failure with reduced ejection fraction
- To assess the optimum order of initiating CHF therapy using enalapril or bisoprolol for 6 months followed by their combination for 6 to 24 months
- Multi-centered, double blinded, randomized control trial with two parralel groups
- Monotherapy with bisoprolol (target dose 10 mg daily) or enalapril (target dose 10 mg BID) x 6 months followed by their combination for 6 to 24 months
- 1,010 patients
- At least 65 years of age
- Mild to moderate CHF (NYHA II or III)
- LVEF of ≤ 35% measured within 3 months before randomization
- Clinically stable CHF symptoms for 7 days before randomization
- On a stable medical regimen for at least 2 weeks including diuretic and ACE (if tolerated)
- Treatment with ace-inhibitor, beta blocker, or ARB for > 7 days during 3 months before randomization
- Acute coronary syndrome within 3 months before randomization
- PCI or CABG planned or performed within 3 months before randomization
- Stroke within 1 month or with permanent neurological sequelae within 6 months before randomization
- HR < 60 beats/min without a functioning pacemaker
- Supine systolic blood pressure < 100 mm Hg at rest
- Electrolyte disturbances
- AV block greater than first degree without a functioning pacemaker
- Obstructive lung disease contraindicating bisoprolol treatment
- 1.3 years
- Time to the first event of combined all-cause mortality or all-cause hospitalization
- Combined at the end of monotherapy phase and the individual components of the primary end point at the study end and at the end of the monotherapy phase
- CV death
- CV hospitalization
- 505 patients with bisoprolol first treatment compared to 505 patients with enalapril first treatment.
- Bisoprolol first treatment was non-inferior to enalapril first treatment.
- In the intention to treat sample, primary endpoint was not significantly different between bisoprolol first compared to enalapril first (HR 0.94; 95% CI 0.77 to 1.16).
- In the per protocol sample, primary endpoint was not significantly different between bisoprolol first compared to enalapril first (HR 0.97; 95% CI .78 to 1.21).
TAKE AWAY: Although non-inferiority of bisoprolol first versus enalapril first treatment was not proven in the per protocol analysis, it may be safe and efficacious to initiate treatment with bisoprolol as with enalapril.
Reference: Willenheimer R, van Veldhuisen DJ, Silke B, et al. Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III. Circulation. 2005;112(16):2426-35.