Comparison of 162 mg and 81 mg Aspirin for Prevention of Preeclampsia: A Randomized Controlled Trial

To compare the efficacy of 162 mg vs 81 mg aspirin daily for the prevention of preterm preeclampsia (less than 37 weeks of gestation) or preeclampsia with severe features among pregnant people at high risk.

We conducted a pragmatic, randomized, open-label, blinded endpoint clinical trial. Pregnant people at high risk for preeclampsia were randomized to treatment with either 162 mg or 81 mg aspirin daily beginning before 16 weeks of gestation until term and followed up until 6 weeks postpartum. The primary composite outcome of either preterm preeclampsia or preeclampsia with severe features was adjudicated by independent researchers blinded to treatment group. Secondary outcomes were the components of the composite, adherence to therapy, and maternal and neonatal complications. The anticipated incidence of the primary composite outcome in the 81-mg group was 8.6%. We calculated that enrollment of 394 participants (197 for each group) would have 80% power to detect a 7.1% reduction in the primary outcome with 162 mg aspirin compared with 81 mg, assuming a two-sided α of 0.05.

Of 400 participants randomized, 365 had delivery data available and were included in the intention-to-treat analysis, with 184 participants in the 162-mg group and 181 in the 81-mg group. The incidence of preterm preeclampsia or preeclampsia with severe features was 26 of 184 (14.1%) in the 162-mg group compared with 31 of 181 (17.1%) in the 81-mg group (relative risk 0.83, 95% CI, 0.51-1.33, P =.4). Individual outcomes of preterm preeclampsia and term preeclampsia with severe features were similar between aspirin groups. Adherence rates ranged from 88% to 91% and 89% to 92% for the 162-mg group compared with the 81-mg group, respectively, across study visits. Singleton birth weight was slightly lower in the 162-mg group (2.9 kg vs 3.2 kg, P =.005). There were eight cases of placental abruption in participants randomized to 162 mg compared with 0 in those randomized to 81 mg ( P =.013).

Among people at increased risk for preeclampsia, the rates of preterm preeclampsia or preeclampsia with severe features were similar to rates in those randomized to treatment with either 81 mg or 162 mg aspirin at less than 16 weeks of gestation.

ClinicalTrials.gov , NCT04070573.