Chronopharmacology of aspirin: administration-time dependent effects on blood pressure in women at high risk for preeclampsia

This study extends previous results on the effects of low-dose aspirin (ASA) on blood pressure (BP) in pregnant women who were at a higher risk of developing preeclampsia than the general obstetric population and who received ASA at different times of the day according to their rest-activity cycle. A double-blind, randomized, controlled trial was conducted in 341 pregnant women (181 primipara) randomly assigned to 1 of 6 possible groups according to treatment (either placebo or ASA, 100 mg/day, starting at 12-16 weeks of gestation) and the time of treatment: on awakening (Time-1), 8 hours after awakening (Time-2), or before bedtime (Time-3). BP for each woman was automatically monitored for 48 consecutive hours every 4 weeks from the day of recruitment until delivery, as well as at puerperium. The women under investigation provided a total of 2511 BP profiles. Effects of medication and time of ingestion upon BP were evaluated by ANOVA. There was no effect of ASA on BP at Time-1 (compared with placebo). A BP reduction was, however, highly statistically significant when ASA was given at Time-2 and, to a greater extent, at Time-3 (mean reductions of 12.6/8.5 mm Hg in 24-hour mean for systolic/diastolic BP at the time of delivery as compared to placebo given at bedtime). Differences in BP among women receiving ASA at different circadian times disappeared at puerperium (P>0.096). There was no effect of ASA or placebo on heart rate at any time of administration. Results indicate a highly significant effect of ASA on BP that is markedly dependent on the time of ASA administration with respect to the rest-activity cycle. Timed use of ASA at low dose effectively contributes to BP control in women at high risk for preeclampsia and could thus eventually reduce the incidence of hypertensive complications in pregnancy, as previously documented [Hermida et al. Hypertension. 1999;34:1016-1023]. SUPPORT: DGES, PM98-0106; PGICT00-PXI-32205PN; Univ. Vigo.