In a previous forced-titration trial, mibefradil 100 mg QD was as effective as amlodipine 10 mg QD in reducing sitting diastolic blood pressure (SDBP), and it produced significantly less leg edema than did amlodipine 10 mg QD. The present multicenter, double-masked, randomized, parallel-design trial was performed to assess the reproducibility of these results using a flexible-titration design. Following a 4-week, single-masked, placebo run-in period, 296 patients with a trough SDBP of between 95 and 114 mm Hg (21 to 27 hours postdose) were randomized to receive once-daily treatment with mibefradil 50 mg (n = 146) or amlodipine 5 mg (n = 150). In patients whose trough SDBP was greater than 90 mm Hg after 4 or 8 weeks of double-masked therapy, the dosage was titrated upward to mibefradil 100 mg or amlodipine 10 mg for the remainder of the 12-week active treatment period. A greater proportion of amlodipine-treated patients (65%) than of mibefradil-treated patients (54%) required titration to the higher dose. Despite this difference, statistically equivalent reductions in trough SDBP were observed after 12 weeks of treatment with 50 to 100 mg of mibefradil QD (−11.7 ± 6.4 mm Hg) and 5 to 10 mg of amlodipine QD (−11.9 ± 6.9 mm Hg). SDBP was normalized to ≤90 mm Hg at week 12 in 66% of patients treated with mibefradil and 65% of those receiving amlodipine. The tolerability profile of mibefradil was superior to that of amlodipine, with significantly fewer patients (P = 0.009) reporting leg edema after mibefradil treatment (7%) than after amlodipine treatment (17%). The results of this study confirm those of the previous trial. Once-daily treatment with mibefradil 50 to 100 mg for 12 weeks was as effective as 12 weeks of once-daily treatment with amlodipine 5 to 10 mg in reducing SDBP and was associated with a significantly lower incidence of leg edema.
