INFLUENCE OF CHRONOTHERAPY WITH DIFFERENT ANTIHYPERTENSIVE DRUGS ON CIRCADIAN BLOOD PRESSURE PATTERN

Abstract

Aim. To determine the value of different blood pressure (BP) measurement methods for arterial hypertension (HT) chronotherapy efficacy assessment. Material and methods. Two similar open, randomized, cross-over studies (morning vs evening intake) were carried out. Duration of the initial wash-out period was 2 weeks; duration of both treatment courses — 3 weeks; the interval between courses — 1 week. Only patients with stable HT (mean day-time BP>135/85 mm Hg) were included. Ambulatory BP monitoring (ABPM) was carried out prior to treatment and at the end of both treatment courses. The patients performed home BP monitoring (HBPM) throughout the study. Pharmacokinetics of verapamil (n=14, mean daily dose — 240.0±16.3 mg) was studied to assess compliance with verapamil therapy. In ramipril trial (n=30) its mean daily dose was 8.9±0.7 mg. The following main ABPM variables were analyzed: ABPM means and variability, maximal and minimal values, nocturnal BP fall, parameters of Fourier transformation and smoothness index. The morning and evening BP means and morning BP surge (morning – evening BP) were assessed by HBPM. Student’s t-value and Mahalanobis distance were used to evaluate individual value of each variable (“morning” vs “evening” effect). This analysis was first done separately for each trial. After that, combined data were analyzed. Results. Overall antihypertensive effect was more intense with morning ramipril (p<0.05) intake and evening verapamil intake. The t-values ranged 2.2-2.3 for nocturnal BP fall; 2.0-2.1 for night-time BP variability; 3.8-4.3 for morning BP surge. The t-values of office and 24-hour BP were low (0.2-1.7). Conclusion. Morning BP surge based on HBPM is a good instrument for chronotherapy effect assessment. Evening administration of antihypertensive drugs causes nocturnal BP fall shift towards “dipper” status.