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 therap eutic effects of a single dose of lercanidipine in patients with angina pec toris, Background: The calcium channel blocker lercanidipine is a new lipophilic, vasoselective dihydropyridine derivative with a slow onset and long duratio n 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 angi na pectoris and angiographically documented coronary artery disease receive d 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 h ours after dosing, Systolic and diastolic blood pressures and heart rate we re assessed both at rest and during exercise, Results: Because of the small number of patients and high variability betwe en the groups, no significant difference was seen compared with placebo, Ne vertheless, 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 co mpared with baseline, and the maximal ST-segment depression decreased signi ficantly 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. H eart rate, systolic blood pressure, and rate-pressure product remained unch anged at rest and during exercise after active treatment (all doses). No ad verse effects caused by reflex tachycardia or acute hypotension were report ed. Conclusions: Our data indicated that the acute administration of lercanidip ine 10 mg to 40 mg in patients with stable exercise-induced angina pectoris caused no unfavorable change in myocardial oxygen consumption and mas well tolerated.