In patients with coronary artery disease nicardipine improved L.V. diastolic distensibility during the early filling phase, probably due to a faster rate of myocardial relaxation in previously underperfused areas. There is little or no effect on normal myocardium, suggesting the improvement is mainly by indirect mechanisms such as afterload reduction, and reduced ischemia. Nicardipine has no negative effect on myocardial relaxation at therapeutic doses. The clinical consequences of these properties are as yet undemonstrated.

Electrophysiologic Effects

In general, no detrimental effects on the cardiac conduction system were seen with the use of nicardipine HCl.

Nicardipine HCl increased the heart rate when given intravenously during acute electrophysiologic studies, and prolonged the corrected QT interval to a minor degree. The sinus node recovery times and SA conduction times were not affected by the drug. The PA, AH and HV intervals* and the functional and effective refractory periods of the atrium were not prolonged by nicardipine HCl and the relative and effective refractory periods of the His-Purkinje system were slightly shortened after intravenous nicardipine HCl.

* PA = conduction time from high to low right atrium, AH = conduction time from low right atrium to His bundle deflection, or AV nodal conduction time, HV = conduction time through the His bundle and the bundle branch-Purkinje system.

Renal Function

There is a transient increase in electrolyte excretion, including sodium. Nicardipine HCl does not cause generalized fluid retention, as measured by weight changes, though 7-8% of patients experience pedal edema..

Effects in Angina Pectoris

In controlled clinical trials of up to 12 weeks duration in patients with chronic stable angina, nicardipine HCl increased exercise tolerance and reduced nitroglycerin consumption and the frequency of anginal attacks. The antianginal efficacy of nicardipine HCl (20-40 mg) has been demonstrated in four placebo-controlled studies involving 258 patients with chronic stable angina. In exercise tolerance testing, nicardipine HCl significantly increased time to angina, total exercise duration and time to 1 mm ST segment depression. Included among these four studies was a dose-definition in which dose-related improvements in exercise tolerance at one and four hours post-dosing and reduced frequency of anginal attacks were seen at doses of 10, 20 and 30 mg TID. Effectiveness at 10 mg TID w.s. however, marginal. In a fifth placebo-controlled study, the antianginal efficacy of nicardipine HCl was demonstrated at 8 hours post-dose (trough). The sustained efficacy of nicardipine HCl has been demonstrated over long-term dosing. Blood pressure fell in patients with angina by about 10/8 mmHg at peak blood levels and was little different from placebo at trough blood levels.

Effects in Hypertension

Nicardipine HCl produced dose-related decreases in both systolic and diastolic blood pressure in clinical trials. The antihypertensive efficacy of nicardipine HCl administered three times daily has been demonstrated in three placebo-controlled studies involving 517 patients with mild to moderate hypertension. The blood pressure responses in the three studies were statistically significant from placebo at peak (1 hour post-dosing) and trough (8 hours post-dosing) although it is apparent that well over half of the antihypertensive effect is lost by the end of the dosing interval. The results from placebo controlled studies of nicardipine HCl given three times daily are shown in the following tables.

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