Background: Mibefradil was recently withdrawn from the market because of an
unfavorable clinical profile in patients with chronic heart failure. Altho
ugh drug interactions appear to play a role, other mechanisms such as proar
rhythmia and autonomic deterioration could also be relevant. Chronic heart
failure is accompanied by autonomic impairment and analysis of heart rate v
ariability can be used to examine autonomic modulation of heart rate. Metho
ds: 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. He
art 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<0.0
5). After 7 months of treatment a reduction in (24-h) heart rate was observ
ed (P=0.02, versus placebo). Apart from the effect on mean NN, no significa
nt differences were observed for the remaining heart rate variability param
eters. Conclusions: Mibefradil does not impair autonomic balance and in fac
t reduces heart rate in patients with heart failure. These findings suggest
that autonomic activation did not contribute to the adverse effects of mib
efradil. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.