Efficacy of mibefradil compared with amlodipine in suppressing exercise-induced and daily silent ischemia: results of a multicenter, placebo-controlled trial.

BACKGROUND: Mibefradil is a new benzimidazolyl-substituted tetraline-derivative calcium antagonist. Its vasodilatory activity combined with an ability to lower heart rate without negative inotropic effects as well as its long duration of action make it a promising anti-ischemic agent. METHODS AND RESULTS: Three hundred nine patients with coronary artery disease, stable angina pectoris, and positive exercise tests were randomized to receive mibefradil (50, 100, or 150 mg), amlodipine (10 mg), or placebo. The anti-ischemic effects of mibefradil on exercise test and silent ischemia parameters were assessed. At doses of 100 and 150 mg, mibefradil increased exercise duration (by 55.5 and 51.0 seconds, respectively; P<.001 for both), increased time to onset of angina (by 98.3 and 82.7 seconds, respectively; P<.001), and increased time to 1-mm ST depression (by 81.7 and 94.3 seconds, respectively; P<.001). By comparison, a 10 mg/d dose of amlodipine significantly improved only time to onset of angina (treatment effect: 38.5 seconds, P=.036). Mibefradil 100 mg and 150 mg decreased the number of episodes of silent ischemia (treatment effects: -3.1 and -3.6, respectively; P<.001) and the duration of silent ischemia (treatment effects: -9.2 minutes, P=.048, and -14.6 minutes, P=.002, respectively). The decrease in the number of episodes of silent ischemia was also statistically significant in the group receiving 10 mg of amlodipine (-1.5; P=.036). CONCLUSIONS: Once-daily doses of 100 and 150 mg mibefradil were effective in improving exercise tolerance and reducing ischemic episodes during ambulatory monitoring in patients with coronary artery disease.

Mibefradil, a novel calcium antagonist, in elderly patients with hypertension: favorable hemodynamics and pharmacokinetics.

A multicenter, double-blind, placebo-controlled study of 310 elderly patients with mild-to-moderate essential hypertension was conducted in 20 sites throughout Europe, Brazil, and Israel to assess the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel calcium antagonist mibefradil in the elderly. Patients were randomly assigned to receive once-daily doses of 6.25, 12.5, 25, 50, or 100 mg of mibefradil or placebo for 4 weeks. Statistically significant and clinically relevant reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) were observed with the 50 and 100 mg doses. Therapeutic responses reached 88.5% for SDBP and 76.5% for SSBP in the 100 mg group. Trough/peak ratios were > 75% in SDBP and SSBP with the 50 mg and 100 mg doses. At doses of 50 to 100 mg once daily, mibefradil was well tolerated and effective with a high antihypertensive response rate and consistent 24-hour blood pressure control in elderly patients.

The impact of near-patient testing on the organisation and costs of an anticonvulsant clinic.

A near-patient testing facility was provided at an anticonvulsant clinic and compared with the previously offered service. Productivity was increased by over 20%, with savings in medical and nursing staff time. This saving in time is offset by increased consumable costs but still enables a significant net saving.