EVALUATING THE SAFETY OF MIBEFRADIL, A SELECTIVE T-TYPE CALCIUM-ANTAGONIST, IN PATIENTS WITH CHRONIC CONGESTIVE-HEART-FAILURE

Mibefradil is a novel calcium antagonist belonging to a new chemical c lass of benzimidazolyl-substituted tetraline derivatives. The safety o f mibefradil in patients with mild-to-moderate chronic congestive hear t failure (CHF) due to coronary heart disease was assessed in a random ized, double-masked, placebo-controlled, multiple-ascending-dose trial in 45 patients. Patients were assigned to receive one of five dose le vels (6.25, 12.5, 25, 50, or 100 mg/d) of mibefradil or placebo accord ing to a randomization list. If safety variables remained stable, the subsequent group of patients was randomized to the next higher dose. T he safety variables assessed included New York Heart Association class , vital signs, and ejection fraction. Patients were evaluated at basel ine and day 8 of the dosing period. Mibefradil did not worsen clinical or cardiac variables. Approximately 23.3% (7 of 30) of the mibefradil -treated patients reported one or more adverse events compared with 13 .3% (2 of 15) of the placebo group. The incidence of adverse events wa s not dose dependent. In summary, short-term oral dosing of mibefradil did not worsen measures of cardiac function in 30 patients with mild- to-moderate CHF.