Toward a personalized chronotherapy of blood pressure

Background: A consensus regarding the optimal time to administer anti-hypertensive medications has not been reached. Possible differential effects of different anti-hypertensive drugs on the circadian pattern of blood pressure (BP) and differential responses of individual patients receiving the same treatment at different times of the day may partly account for the controversy. Methods: Ambulatory blood pressure monitoring (ABPM) data available at 30-min intervals for 7 days from previous studies are reanalyzed to compare the effect of five drugs (amlodipine, atenolol, captopril retard, long-acting carteolol, and nilvadipine) taken 1.5 h after awakening or twice a day on the 24-h profile of BP from 7 to 13 conventionally diagnosed patients per treatment group. Similar data from 30 patients receiving losartan/hydrochlorothiazide for at least one month at each of six different times in relation to their time of awakening serve to compare the effect of treatment time in different patients. Results: Some but not all drugs affected the 24-h amplitude and/or phase of BP or the contribution of the 12-h harmonic term to modify the circadian waveform of BP. While evening dosing increased the 24-h amplitude of BP in some patients, other patients achieved such a desired effect with morning dosing. Conclusion: Personalized optimization of treatment timing to best match a healthy circadian BP pattern is recommended, guided by chronobiological analyses of ABPM data collected over several days in view of the large day-to-day variability in all features of the 24-h BP rhythm.