Administration Time–Dependent Influence of Aspirin on Blood Pressure in Pregnant Women

Abstract
This study prospectively investigates the potential influence of low-dose aspirin on blood pressure in pregnant women who were at a higher risk of developing preeclampsia than that of the general obstetric population and who received aspirin 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 aspirin, 100 mg/day, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Blood pressure was automatically monitored for 48 consecutive hours every 4 weeks from the day of recruitment until delivery, as well as at puerperium. There was no effect of aspirin on blood pressure at time 1 (compared with placebo). A blood pressure reduction was highly statistically significant when aspirin was given at time 2 and, to a greater extent, at time 3 (mean reductions of 9.7/6.5 mm Hg in 24-hour mean for systolic/diastolic blood pressure at the time of delivery as compared with placebo given at bedtime). Differences in blood pressure among women receiving aspirin at different circadian times disappeared at puerperium ( P >0.096). Results indicate a highly significant effect of aspirin on blood pressure that is markedly dependent on the time of aspirin administration with respect to the rest-activity cycle. Timed use of aspirin at low dose effectively contributes to blood pressure control in women at high risk for preeclampsia.