Abstract
OBJECTIVE:To evaluate whether daily enoxaparin, added to low-dose aspirin, started before 14 weeks of gestation reduces placenta-mediated complications in pregnant women with previous severe preeclampsia diagnosed before 34 weeks of gestation.METHODS:In this open-label multicenter randomized trial, we enrolled consenting pregnant women with previous severe preeclampsia diagnosed before 34 weeks of gestation, gestational age at randomization of 7-13 weeks, singleton pregnancy, and no plan for anticoagulation. Eligible patients were randomly assigned to a one-to-one ratio to receive daily either 4,000 international units enoxaparin plus 100 mg aspirin or 100 mg aspirin alone. Randomization was done by a web-based randomization system. The primary composite outcome comprised maternal death, perinatal death, preeclampsia, small for gestational age (less than the 10th percentile), and placental abruption. A sample size of 232 women equally divided into two groups was needed to detect a significant reduction in primary outcome from 55% in the aspirin group to 36.7% in the enoxaparin-aspirin group (α: 0.05, β: 0.8, two-sided).RESULTS:Between November 14, 2009, and February 21, 2015, 257 participants were enrolled. Baseline demographic and clinical factors were similar between groups. Eight women were excluded after randomization (six in the enoxaparin-aspirin group and two in the aspirin group), leaving 124 participants assigned to enoxaparin-aspirin and 125 to aspirin. Five participants were lost to follow-up (two in the enoxaparin-aspirin group and three in the aspirin group). There was no significant difference between the groups in the primary outcome: enoxaparin-aspirin 42 of 122 (34.4%) compared with aspirin alone 50 of 122 (41%) (relative risk 0.84, 95% confidence interval 0.61-1.16, P=.29). The occurrence of complications did not differ between the two groups.CONCLUSION:Antepartum prophylactic enoxaparin does not significantly reduce placenta-mediated complications in women receiving low-dose aspirin for previous severe preeclampsia diagnosed before 34 weeks of gestation.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, https://clinicaltrials.gov, NCT00986765.