Effect of Mibefradil, a T-Type Calcium Channel Blocker, on Morbidity and Mortality in Moderate to Severe Congestive Heart Failure

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Abstract
Background —Calcium antagonists have proved disappointing in long-term congestive heart failure (CHF) studies. Mibefradil, a new calcium antagonist that selectively blocks T-type calcium channels, has been shown to be an effective antihypertensive, antianginal, and anti-ischemic agent, and because of its different mechanism of action, it may be beneficial as adjunct therapy in CHF patients. Methods and Results —This multicenter, randomized, double-blind study compared mibefradil with placebo as adjunct to usual therapy in 2590 CHF patients (NYHA class II to IV; left ventricular fraction P =0.151). The 14% increased risk of mortality with mibefradil in the first 3 months was not statistically significant ( P =0.093). Treatment groups had similar cardiovascular mortality ( P =0.246), cardiovascular morbidity/mortality ( P =0.783), and reasons for death or hospitalization. Patients comedicated with mibefradil and antiarrhythmics (class I or III), including amiodarone, had a significantly increased risk of death. Substudies demonstrated no significant differences between treatments. Conclusions —When used as adjunct therapy, mibefradil did not affect the usual outcome of CHF. The potential interaction with antiarrhythmic drugs, especially amiodarone, and drugs associated with torsade de pointes may have contributed to poor outcomes early in the study.