Acute dose-response, double-blind, placebo-controlled pilot study of lercanidipine in patients with angina pectoris

Objective: The aim of this double-blind, placebo-controlled, parallel- group, dose-response, pilot study was to assess the acute hemodynamic and therapeutic effects of a single dose of lercanidipine in patients with angina pectoris. Background: The calcium channel blocker lercanidipine is a new lipophilic, vasoselective dihydropyridine derivative with a slow onset and long duration of action that has been shown to be effective in hypertensive patients at a dosage of 10 to 20 mg/d. Methods: Forty-five patients (42 males, 3 females) with chronic stable angina pectoris and angiographically documented coronary artery disease received a single oral dose of lercanidipine 5 mg (n = 7), 10 mg (n = 8), 20 mg (n = 7), 30 mg (n = 7), or 40 mg (n = 8) or of placebo (n = 8). Anti-ischemic and antianginal efficacy was assessed by a bicycle exercise test 3 and 8 hours after dosing. Systolic and diastolic blood pressures and heart rate were assessed both at rest and during exercise. Results: Because of the small number of patients and high variability between the groups, no significant difference was seen compared with placebo. Nevertheless, a significant (P < 0.05) improvement in total exercise duration was observed 3 and 8 hours after dosing compared with baseline in patients receiving lercanidipine 10 mg and 40 mg. A significant improvement in time to ST-segment depression was also observed with all lercanidipine doses compared with baseline, and the maximal ST:segment depression decreased significantly in the 20- and 30-mg lercanidipine groups. An improvement in time to angina was observed with all lercanidipine doses except the 5-mg dose. Heart rate, systolic blood pressure, and rate pressure product remained unchanged at rest and during exercise after active treatment (all doses). No adverse effects caused by reflex tachycardia or acute hypotension were reported. Conclusions: Our data indicated that the acute administration of lercanidipine 10 mg to 40 mg in patients with stable exercise-induced angina pectoris caused no unfavorable change in myocardial oxygen consumption and was well tolerated.