Mid‐gestation aspirin withdrawal and its effects on maternal hemodynamics and uteroplacental Doppler: A post hoc analysis of the StopPRE trial

Objective This study assesses the effect of aspirin discontinuation at 24–28 weeks of gestation on longitudinal trajectories of mean arterial pressure (MAP) and uterine artery pulsatility index (UtAPI) in pregnant women at high risk of preterm preeclampsia with a normal angiogenic profile. Methods This was a post hoc analysis of the multicenter StopPRE randomized trial including 936 women identified as high risk for preterm preeclampsia in the first trimester and treated with aspirin. At 24–28 weeks, participants with a normal soluble fms‐like tyrosine‐kinase 1/placental growth factor ratio (≤38) were randomized to either continue aspirin until 36 weeks ( n = 463) or discontinue treatment ( n = 473). Serial measurements of MAP and UtAPI were obtained until delivery. Longitudinal trajectories were compared between groups using linear mixed‐effects models, including an interaction term between gestational age and treatment group. Results A total of 2977 MAP and 2939 UtAPI measurements were analyzed. MAP increased and UtAPI decreased with advancing gestational age in both groups. There were no significant differences between continuation and discontinuation groups in the trajectories of MAP or UtAPI (group–time interaction P = 0.623 and P = 0.498, respectively). Results were consistent when values were expressed as multiples of the median and in sensitivity analyses restricted to women with ≥90% treatment adherence. No differences were observed when analyses were stratified by the development of preterm preeclampsia. A significant reduction in UtAPI percentiles was observed from the first trimester to mid‐pregnancy. Conclusion Discontinuation of aspirin at 24–28 weeks of gestation in high‐risk pregnancies with a normal angiogenic profile does not affect longitudinal trajectories of MAP or UtAPI. These findings provide indirect supportive evidence regarding the pharmacodynamic effects of aspirin withdrawal at mid‐gestation and suggest that its beneficial effects on uteroplacental perfusion might occur earlier in pregnancy.