Effect of amlodipine on the survival of patients with severe chronic heart failure due to a nonischemic cardiomyopathy: Results of the PRAISE-2 study (prospective randomized amlodipine survival evaluation 2)

Objectives: This study was designed to test the hypothesis of whether amlodipine reduces the risk for death in patients with heart failure due to a nonischemic cardiomyopathy. Background: A pre-specified subgroup analysis in an earlier, large-scale, placebo-controlled study suggested that amlodipine might reduce the risk for death in patients with heart failure due to a nonischemic cardiomyopathy. Methods: To evaluate this hypothesis, 1654 patients with severe heart failure due to a nonischemic cardiomyopathy (ejection fraction<30%) were randomly assigned to amlodipine (target dose: 10 mg/d) or placebo added to conventional therapy for heart failure for a median of 33 months. Results: There were 278 deaths in the amlodipine group and 262 deaths in the placebo group (hazard ratio: 1.09; 95% confidence interval [CI]: 0.92 to 1.29; p= 0.33). The differences between the 2 groups in the risks for cardiovascular death and hospitalization were also not significant. When the results from patients with a nonischemic cardiomyopathy in both the earlier trial and in the current study were combined, there was no evidence of a favorable or unfavorable effect of amlodipine on mortality (hazard ratio: 0.97; 95% CI: 0.83 to 1.13; p= 0.66). Both trials, however, observed higher frequencies of peripheral edema and pulmonary edema and lower frequencies of uncontrolled hypertension and chest pain in patients treated with amlodipine. Conclusions: These results of the current trial, viewed together with the results from the earlier study, indicate that amlodipine does not exert favorable effects on the clinical course of patients with heart failure, regardless of the presence or absence of underlying coronary artery disease. These findings indicate the need for great caution when striking benefits are observed in subgroups of patients or in trials not primarily designed to assess such effects.