Carvedilol versus placebo for patients with congestive heart failure and left ventricular ejection fraction < 40%
Topic: Beta-blockers for heart failure with reduced ejection fraction
Aim:
- Sympathetic antagonist, with carvedilol, may improve survival and morbidity in patients with heart failure with reduced ejection fraction.
Design:
- Multi-centered, double blinded, randomized control trial
Treatment:
- Initial dose: Carvedilol 6.25 mg PO BID
- Target dose: Carvedilol 25-50 mg PO BID
Control:
- Placebo
Cohort:
- 1,094 patients
Inclusion criteria:
- Symptoms of HF for > 3 months
- Ejection fraction ≤ 35% despite ACE-inhibitor and diuretic
Exclusion criteria:
- Major CV event or surgery within 3 months
- Uncorrected, primary valvular disease
- Active myocarditis
- Sustained VT or or advanced heart block not corrected by pacemaker or AAD
- SBP >160 mm Hg or SBP < 85 mm Hg or DBP < 100 mm Hg
- HR < 68 BPM
- Clinically important hepatic or renal disease
- Any condition other than HF that could limit survival
- Treatment with alpha or beta agonist or blocker, CCB, or class IC or III AAD
Follow up:
- 6 months
Primary endpoint:
- Overall survival
Secondary endpoint:
- Hospitalization for heart failure or other CV causes
Main results:
- Overall mortality rate was 7.8% in placebo vs 3.2% in carvedilol group.
- The reduction in risk attributable to carvedilol was 65% for mortality (p < 0.0001).
- Carvedilol therapy was accompanied by 27% reduction in risk in hospitalization for CV cause (p = 0.03) and 38% reduction in combined rate of hospitalization or death (p < 0.001).
TAKE AWAY: Carvedilol reduces risk of death and risk of hospitalization for CV causes in patients with HF who are receiving digoxin, diuretic, and an ACE-I.
