Double-Blind, randomized comparative study of the antihypertensive effect of nicardipine slow-release and nifedipine slow-release in hypertensive patients with coronary heart disease
The main aim of this study was to investigate whether a new slow-release formulation of nicardipine can control hypertension and whether its antihypertensive effect is manifest throughout the dose intervals. In a randomized, double-blind placebo-controlled study, the antihypertensive effect of two calcium antagonists (Type II) was investigated in two independent groups of hypertensive patients with coronary artery disease. One group of patients received 40 mg nicardipine slow-release b.i.d. and the other 20 mg nifedipine slow-release b.i.d. The effect of the active drugs on blood pressure (BP), heart rate, and hemodynamics was compared with placebo within each group. In addition, a group comparison was made to establish whether nicardipine had any advantage over nifedipine. Twenty-eight patients [27 female, 1 male; 55 (41–72) years old], 18 with previous myocardial infarction (MI) entered the study (nicardipine, 15 patients; nifedipine, 13 patients). A placebo period of 3 days was followed by a 13-day drug treatment period. From the first to last trial day, BP and heart rate were measured three times daily. At the end of the placebo and the active drug periods, the following measurements were caried out: ambulatory BP monitoring by half-hourly recording for 12.5 hours with the Remler system, ergometric tests with ECG, and right heart catheterization. Both drugs lowered the BP at rest, during exercise, and during usual daily activities. The antihypertensive effect of nicardipine was significant for the daytime mean arterial BP (MAP) and for systolic BP and diastolic BP at various stages of the exercise tests. The difference between the effect of nicardipine and nifedipine was not significant. The BP profiles were, in general, at a lower level with both active drugs in comparison to placebo. The exception was the diastolic BP, especially of the nicardipine patients, in the afternoon about 10 hours after the morning medication. Heart rate increased slightly in both groups under ambulatory conditions, but was more pronounced with exercise load. The BP variability, with mean values of about 46 mmHg for systolic BP and 28 mmHg for diastolic BP, was identical within the groups with placebo and with active drugs. There was no influence on the double product, effort tolerance, ST-segment depression, and the hemodynamic parameters. Adverse effects observed during the study were mild and transient. Although this slow-release formulation of nicardipine was proven to have an overall antihypertensive effect, the study results call for improving the formulation to ensure a sustained antihypertensive effect between dose intervals. Neither of the two tested slow-release formulations show any advantage.