Effect of mibefradil on heart rate variability in patients with chronic heart failure

Background: Mibefradil was recently withdrawn from the market because of an unfavorable clinical profile in patients with chronic heart failure. Although drug interactions appear to play a role, other mechanisms such as proarrhythmia and autonomic deterioration could also be relevant. Chronic heart failure is accompanied by autonomic impairment and analysis of heart rate variability can be used to examine autonomic modulation of heart rate. Methods: We studied 18 heart failure patients (age 63.2±10.1 years (mean±S.D.), ejection fraction 0.21±0.07) treated with mibefradil or placebo, who participated in the MACH-I (Mortality Assessment in Chronic Heart failure) trial in our center, and compared them with 18 healthy matched controls. Heart rate variability analysis was performed at baseline and after 7 months of treatment. Results: At baseline, heart rate variability parameters were impaired in patients with heart failure compared to healthy controls (P<0.05). After 7 months of treatment a reduction in (24-h) heart rate was observed (P=0.02, versus placebo). Apart from the effect on mean NN, no significant differences were observed for the remaining heart rate variability parameters. Conclusions: Mibefradil does not impair autonomic balance and in fact reduces heart rate in patients with heart failure. These findings suggest that autonomic activation did not contribute to the adverse effects of mibefradil.