Mibefradil in the treatment of systemic hypertension: comparative studies with other calcium antagonists

Abstract

This paper summarizes the results of 4 double-blind studies of antihypertensive therapy in which mibefradil was compared with other commonly used calcium antagonists (diltiazem CD, amlodipine, nifedipine SR, and nifedipine GITS) at the recommended dose range. A total of 640 patients were included, with 361 randomized to mibefradil, 98 to diltiazem CD, 119 to amlodipine, 71 to nifedipine SR, and 36 to nifedipine GITS. Trials included an active treatment phase of 6 or 12 weeks in duration. Compared with diltiazem CD or nifedipine SR, mibefradil demonstrated statistically significant greater efficacy. Decreases in sitting diastolic blood pressure (SDBP) after treatment with mibefradil 100 mg once daily were 14.0 +/- 7.8 mm Hg compared with 9.5 +/- 7.5 mm Hg with diltiazem CD 360 mg once daily (p = 0.001), and 12.8 +/- 8.4 mm Hg compared with 8.1 +/- 19.2 mm Hg with nifedipine SR 40 mg twice daily (p = 0.014). Patients on mibefradil also had higher normalization (SDBP reduced to < or = 90 mm Hg) and response (SDBP reduction > or = 10 mm Hg or normalization) rates than did those on diltiazem CD or nifedipine SR. The overall incidence of adverse events was similar among these 3 compounds, but the number of premature withdrawals due to adverse events was greater with both comparators than with mibefradil. Treatment with 100 mg mibefradil or 10 mg amlodipine once daily resulted in statistically significant decreases from baseline in SDBP of 11.5 +/- 8.2 mm Hg and 13.2 +/- 7.9 mm Hg, respectively, which were statistically equivalent. However, patients treated with amlodipine had a considerably greater incidence of leg edema than did those treated with mibefradil (33.6% vs 4.2%, respectively). Similarly, 100 mg mibefradil was equivalent in efficacy to 60 mg nifedipine GITS once daily, but patients on mibefradil experienced fewer vasodilatory related adverse events. In summary, mibefradil demonstrated superior efficacy to diltiazem CD and nifedipine SR and equivalent efficacy to amlodipine and nifedipine GITS in the treatment of hypertension.