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
Aim:
- 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
Design:
- Multi-centered, double blinded, randomized control trial with two parralel groups
Treatment:
- 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
Cohort:
- 1,010 patients
Inclusion criteria:
- 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)
Exclusion criteria:
- 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
Follow up:
- 1.3 years
Primary endpoint:
- Time to the first event of combined all-cause mortality or all-cause hospitalization
Secondary endpoint:
- 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
Main results:
- 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.
