A Double-Blind, Controlled, Multicenter, Randomized Study Comparing the Antihypertensive Effectiveness and Tolerance of a Daily Dose of Two Nifedipine Formulations: Nifedipine Microgranules Versus Nifedipine Osmotic Pump

Abstract

Controlled clinical studies have clearly established the advantages of blood pressure (BP) reduction. However, optimal control of BP in the population is still not adequate. Monotherapy is ineffective in the majority of hypertensive patients, and multidrug therapy increases costs. The objective of the study was to assess to what extent and how uniformly BP can be controlled with two different 24-hour drug-releasing formulations of nifedipine, used as monotherapy. One hundred ninety-two patients of both genders, aged 18 to 65 years, with mild to moderate (Stage 1 and 2) essential hypertension with systolic BP <200 mm Hg and diastolic BP between 90 and 115 mm Hg were randomized in a double-blind, double-dummy fashion to receive sustained-release formulations of 30 mg nifedipine/day either as microgranules (NMG) or via osmotic pump (NOP) for 8 weeks. Office BP was measured at baseline (after 2 weeks of placebo) and after the third to fourth week of treatment. If at the third to fourth week the systolic BP/diastolic BP did not reach values of <140/<90 mm Hg, the dose was doubled to 60 mg/day. Monotherapy that did not yield these BP values at 8 weeks was considered a failure. Ambulatory monitoring of blood pressure (AMBP) was also performed after the placebo period and at the end of treatment. Smoothness index (SI) and trough/peak ratio (T/P) were calculated and their correlation was checked. The initial systolic/diastolic BP values were similar at baseline and decreased significantly after the third to fourth week of treatment, with no difference between the groups. The proportions of patients reaching the goal BP (<140/<90 mm Hg) were similar in the two groups: NMG, 71%, and NOP, 78% (P = 0.12). There were no changes in the heart rate in either group. There was no difference between groups in the reduction in mean arterial pressure measured by AMBP. The frequency of SI values >1.4 and T/P ratios of >0.5 was similar in both groups. An important correlation was found between the SI and T/P values. The incidence of adverse effects was low and similar in both groups. Target BP was reached in more than 70% of patients receiving monotherapy with either formulation. Both formulations were tolerated well.