Twenty-Four-Hour Antihypertensive Efficacy of Felodipine 10 mg Extended-Release: The Italian Inter-University Study

Abstract

We assessed the 24-h antihypertensive efficacy of an extended-release (ER) 10-mg formulation of the dihydropyridine felodipine in mild-to-moderate essential hypertension [World Health Organization (WHO) stage I-II]. Thirty patients, 23 men and 7 women, aged 37-70 years (mean 53 +/- 9 years) participated in a double-blind, randomized, cross-over study of felodipine 10 mg ER versus placebo. An ambulatory daytime diastolic blood pressure (DBP) >90 mm Hg at the end of a 4-week run-in period was necessary to enter the 10-week treatment phase. Twenty-nine patients completed the treatment phase. Twenty-two underwent a 2-day single-blind placebo follow-up to assess residual drug effects. All patients underwent ambulatory BP monitoring (ABPM) by Spacelabs 90207 recorders. Recorders were programmed to make automatic BP and heart rate (HR) measurements every 15 min throughout the 24 h. Felodipine 10 mg ER significantly (p < 0.01) reduced ambulatory systolic BP (SBP) and DBP values throughout the 24-h, day (7 a.m. to 11 p.m.) and night (11 p.m. to 7 a.m.) periods, but not influencing average ambulatory HR values. Trough-to-peak (T/P) ratios, calculated on the average ambulatory BP values measured in the 7-9 a.m. 2-h interval of the second day of ABPM (before the new drug administration: trough) and in the 10 a.m. to 12 noon 2-h interval of the first day of ABPM (peak BP-lowering effect), were 0.71 and 0.58 for SBP and DBP, respectively. Individual T/P calculations, after post hoc selection of nonresponders, gave superimposable results, the consistency of which was judged on mean, median, and confidence intervals (CI). However, the wide variability of the individual T/P ratios suggests that this method cannot be the only means to evaluate the duration of action of an antihypertensive drug by ABPM. The long-acting BP-lowering drug effect was clearly shown by the ABPM performed in the follow-up when SBP and DBP average values of the 24-h, day, and night periods were still reduced. Felodipine 10 mg ER effectively reduced BP in patients with mild-to-moderate hypertension, showing prolonged duration of its antihypertensive action beyond the time of the next dose.