Differential effects of lercanidipine and nifedipine GITS on plasma norepinephrine in chronic treatment of hypertension

Abstract

This study aimed to compare the effects of two long-acting dihydropyridine calcium channel blockers (CCBs) with different pharmacologic properties, lercanidipine and nifedipine Gastro-Intestinal Therapeutic System (GITS), in the chronic treatment of essential hypertension. After a 4-week placebo run-in period, 60 patients of both sexes were randomly treated with lercanidipine 10 to 20 mg or nifedipine GITS 30 to 60 mg taken orally for 48 weeks, according to a double-blind, parallel group design. For the first 4 weeks of treatment, the lowest dose of each drug was used, followed by higher doses if diastolic blood pressure (BP) was >90 mm Hg. At the end of the placebo period and after 4, 8, 12, 24, and 48 weeks of active treatment BP, heart rate (HR), and plasma norepinephrine (NE) levels were assessed. Lercanidipine and nifedipine GITS similarly reduced BP values after 48 weeks (-21.7/15.9 mm Hg and -20.7/14.6 mm Hg, respectively, both P <.001 v placebo), with no change in HR. Despite the similar lack of effect on HR, the two drugs displayed different influences on plasma NE, which was significantly increased by nifedipine GITS (+56 pg/mL, P <.05 v placebo) but not by lercanidipine. These findings suggest that 1) sympathetic activation occurs during chronic therapy with nifedipine GITS but not with lercanidipine, which might be related to the different pharmacologic characteristics of the two CCBs at the doses evaluated; and 2) nifedipine GITS seems to activate peripheral but not cardiac sympathetic nerves, consistent with differing regulation of cardiac and peripheral sympathetic activity.