Comparative impact of enalapril, candesartan or metoprolol alone or in combination on ventricular remodelling in patients with congestive heart failure

AIMS: RESOLVD study patients were randomized to candesartan (C), enalapril (E), or C+E. Patients were later randomized to metoprolol CR (M) or placebo. Examine impact of C or E (C/E), C+E, C+M/E+M, C+E+M on ventricular remodelling in heart failure (HF) over 43 weeks. METHODS AND RESULTS: Four hundred and twenty-six of 768 patients receiving C, E, or C+E were randomized to either M or placebo. Patients were New York Heart Association class II-IV, ejection fraction (EF) <0.40 and 6-min walk distance <500 m. Ejection fraction (EF), cardiac volumes, blood pressures, heart rates, and neurohormones were measured. End diastolic volumes changed +29.4+/-6.4 ml for C/E, +16.6+/-10.4 ml for C+E, +19.7+/-6.5 ml for C+M/E+M, and -6.4+/-7.5 ml for C+E+M (P< or =0.01). End systolic volumes changed +22.9+/-5.8 ml for C/E, +11.9+/-9.1 ml for C+E, +6.0+/-5.7 ml for C+E/E+M, and -16.5+/-7.0 ml for C+E+M (P< or =0.001). Ejection fraction changed +0.01+/-0.01 for C/E, +0.01+/-0.01 for C+E, +0.03+/-0.01 for C+M/E+M, and +0.05+/-0.01 for C+E+M (P< or =0.0001). No significant differences for blood pressure or neurohormones; heart rate for C+M/E+M and C+E+M decreased (P< or =0.01) vs C/E or C+E. CONCLUSION: C+E+M had a modest but beneficial effect on cardiac function compared to the other groups. Combination of C+E+M has potential for providing HF patients with further benefit.