The acute effects of intravenously administered mibefradil, a new calcium antagonist, on the electrophysiologic characteristics of the human heart

Objective: This multicenter, double-blind, placebo-controlled, parallel-group study was designed to assess the acute effects of intravenous mibefradil on the electrophysiologic characteristics of the human heart. Methods: Seventy-one patients referred for routine electrophysiologic testing were randomized to receive one of three intravenous treatments: placebo n = 23, 15 mg mibefradil in 15 min followed by 25 mg in 60 min (group 1, n = 24), or 35 mg mibefradil in 15 min followed by 45 mg in 60 min (group 2, n = 24). Electrophysiologic evaluations were performed prior to study drug administration and 30 min after the start of the infusion. Plasma samples were obtained at the start of the infusion and after 15, 75, and 105 min. Results: Sinus node recovery time decreased significantly in Group 1 patients (-103 ms). Corrected sinus node recovery time in group 2 patients was 68.7 ms (P = 0.053). Compared to placebo, mibefradil produced mild but significant slowing of conduction in group 2 patients as manifested by an increase in the AH interval of 6.7 ms. Atrioventricular (AV) nodal refractoriness was increased, as indicated by a prolongation of the Wenckebach point in patients in both group 1 (32.1 ms) and group 2 (32.5 ms), compared to placebo. All adverse events were classified as mild to moderate and only one event (vasovagal attack) was considered to be treatment related. Conclusions: At plasma levels close to those found after chronic oral administration of 50 and 100 mg mibefradil, the higher dose produced an increase in corrected sinus node recovery time. Mibefradil also produced small but significant effects on AV nodal conduction and increased AV nodal refractoriness. Mibefradil had no effect on any other electrophysiologic parameter and was well tolerated