Administration time-dependent effects of aspirin in women at differing risk for preeclampsia

This study extends previous results on the effects of low-dose aspirin on b lued pressure in pregnant women at differing risk of developing hypertensio n in pregnancy and who received aspirin at different times according to the ir rest-activity cycle. A double-blind, randomized, placebo-controlled tria l was conducted in 240 pregnant women randomly assigned to 1 of 6 groups ac cording to treatment (placebo or aspirin, 100 mg/d. stm tine at 12 to 16 we eks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Blood pressure and h eart rate for each subject were automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery, as well as at puerperium (6 to 8 weeks after delivery). Subjects were further divided for comparativ e purposes according to the results of the tolerance-hyperbaric test for ea rly identification of those with a higher risk for developing hypertensive complications in pregnancy, Results indicated that there was no effect of a spirin on blood pressure at time 1 (compared with placebo). A blood pressur e reduction was, however, highly statistically significant at time 2 and, t o a greater extent, at time 3 (mean reductions of 14.2 and 9.6 mm Hg in 24- hour means for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). Effects of aspirin on blood pressure wen significantly larger for women with a positiv e test at the time of recruitment (P<0.001). Differences in blood pressure among pregnant women receiving aspirin at different times in the circadian cycle disappeared at puerperium (P>0.212). There was no effect of aspirin o r placebo on heart rate. This study corroborates the statistically signific ant, time-dependent effect of low-dose aspirin on blood pressure in pregnan t women with differing risk of developing hypertensive complications in pre gnancy. Although the mechanism involved in the administration-time-dependen t responsiveness of blood pressure to aspirin still remains uncertain, the use of doses of aspirin <80 mg/d that do not affect placental thromboxane, initiation of the use of aspirin after 16 weeks' gestation, and the lack of circadian timing for aspirin administration could all explain the lack of positive results in previous clinical trials.