Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate

The time of administration of once-daily antihypertensive agents may have a significant impact on blood pressure control during awake and sleep period s. Using 24-h ambulatory monitoring, we compared the effects of morning and evening dosing of the long-acting dihydropyridine calcium channel blocker, nisoldipine extended-release (ER), on circadian blood pressure (BP) and he art rate in patients with mild-to-moderate hypertension. After completing a 3-week placebo run-in period, 85 patients were randomized to morning versu s evening nisoldipine ER treatment at a fixed 20-mg dose. Patients were tre ated for 4 weeks, followed by crossover to the alternate dosing regimen for 4 additional weeks. Twenty-four-hour ambulatory monitoring was performed a t baseline and at 4 and 8 weeks after randomization. Awake and sleep times were determined by electronic activity recorders (Actigraphy). Similar leas t-squares (+/-SE) mean changes from baseline in 24-h BP (systolic BP/diasto lic BP: -11.9/-7.4 +/- 0.6/0.5 v -11.6/-6.5 +/- 0.6/0.5 mm Hg) and heart ra te (1.0/1.7 +/- 0.4/0.4 beats/min) occurred with morning and evening admini stration, respectively. A significantly greater effect on awake diastolic B P (systolic BP/diastolic BP: -12.6/-8.1 +/- 0.7/0.4 v -11.3/-6.4 +/- 0.7/0. 4 mm Hg; P = .16/.01) was observed with morning dosing compared with evenin g dosing. In addition, small increases in sleep and early morning heart rat e were seen with evening compared with mooting administration of nisoldipin e (sleep, 3.1 +/- 0.4 v 0.4 +/- 0.4 beats/min; P < .001; early morning, 3.5 +/- 0.7 v 0.5 +/- 0.7 beats/min; P = .002). These differential effects on awake BP and sleep heart rate were also observed in patients who had normal (dippers) and elevated (nondippers) BP values during sleep. Appropriate ev aluation of the efficacy and safety of long-acting antihypertensive agents is essential when evening administration is being considered. In the presen t study, the timing of nisoldipine ER administration had no effect on mean changes in BP and heart rate over a 24-h period. However, nisoldipine ER ha d some differential effects during sleep and awake periods with morning rel ative to evening dosing. (C) 1999 American Journal of Hypertension, Ltd.