Evaluating the safety of mibefradil, a selective T-type calcium antagonist, in patients with chronic congestive heart failure

Abstract

Mibefradil is a novel calcium antagonist belonging to a new chemical class of benzimidazolyl-substituted tetraline derivatives. The safety of mibefradil in patients with mild-to-moderate chronic congestive heart failure (CHF) due to coronary heart disease was assessed in a randomized, double-masked, placebo-controlled, multiple-ascending-dose trial in 45 patients. Patients were assigned to receive one of five dose levels (6.25, 12.5, 25, 50, or 100 mg/d) of mibefradil or placebo according to a randomization list. If safety variables remained stable, the subsequent group of patients was randomized to the next higher dose. The safety variables assessed include New York Heart Association class, vital signs, and ejection fraction. Patients were evaluated at baseline 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 was 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.