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, paralle l-group study was designed to assess the acute effects of intravenous mibefradil on the electrophysiologic characteristics of the human hear t. Methods: Seventy-one patients referred for routine electrophysiolog ic testing were randomized to receive one of three intravenous treatme nts: placebo n = 23, 15 mg mibefradil in 15 min followed by 25 mg in 6 0 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 pe rformed prior to study drug administration and 30 min after the start of the infusion. Plasma samples were obtained at the start of the infu sion 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). Compa red to placebo, mibefradil produced mild but significant slowing of co nduction in group 2 patients as manifested by an increase in the AH in terval of 6.7 ms. Atrioventricular (AV) nodal refractoriness was incre ased, as indicated by a prolongation of the Wenckebach point in patien ts in both group 1 (32.1 ms) and group 2 (32.5 ms), compared to placeb o. All adverse events were classified as mild to moderate and only one event (vasovagal attack) was considered to be treatment related. Conc lusions: At plasma levels close to those found after chronic oral admi nistration of 50 and 100 mg mibefradil, the higher dose produced an in crease 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 electroph ysiologic parameter and was well tolerated.