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Early Aspirin Discontinuation in Pregnancies at High Risk of Preterm Preeclampsia
Quick Takes
- Discontinuation of aspirin at 24−28 weeks’ gestation may be considered for prevention of preterm preeclampsia in patients with high first trimester risk of preeclampsia and sFlt-1:PlGF ratio <38.
- Early aspirin discontinuation may be associated with decreased risk of minor bleeding or pregnancy complications at 37 weeks’ gestation or more.
Study Questions:
Is discontinuing aspirin in pregnancies at high risk of preterm preeclampsia in the first trimester with a soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio <38 between 24−28 weeks of gestation noninferior to discontinuation at 36 weeks’ gestation to prevent preterm preeclampsia?
Methods:
This was a multicenter, open-label, randomized, phase 3, noninferiority trial conducted at nine hospitals across Spain between August 20, 2019−September 15, 2021. Patients were included if they were ≥18 years old, with a singleton pregnancy, alive fetus, gestational age 24-28 weeks with sFlt-1:PlGF ratio <38, high risk of preterm preeclampsia, and aspirin treatment (150 mg/day) initiated <17 weeks of gestation with ≥50% adherence. Patients were randomly assigned 1:1 to continue (control group, n = 463) or discontinue (intervention group, n = 473) aspirin treatment between 24−28 weeks of gestation. The primary outcome was delivery due to preeclampsia before 37 weeks of gestation (preterm preeclampsia). Secondary outcomes included preeclampsia before 34 weeks of gestation, preeclampsia at or after 37 weeks of gestation, and the presence of any other adverse pregnancy outcome.
Results:
Baseline characteristics were well matched between groups. The primary outcome occurred in 1.48% of patients in the intervention group compared to 1.73% of patients in the control group (95% confidence interval [CI], −1.86% to 1.36%). There was no difference between the median gestational age at delivery for preterm preeclampsia between groups (35.1 weeks). There was no difference between groups related to delivery before 34 weeks of gestation or at or after 37 weeks of gestation. At least one adverse outcome at or after 37 weeks of gestation occurred in fewer patients in the intervention group compared to the control group (13.3% vs. 18.4%; 95% CI, −9.73 to −0.36%). Patients in the intervention group were less likely to experience minor antepartum hemorrhage compared to the control group (7.6% vs. 12.3%; 95% CI, −8.53 to −0.87%). At least one bleeding event occurred in fewer patients in the intervention group compared to the control group (8% vs. 12.7%; 95% CI, −8.61 to −0.81%). The incidence of other bleeding complications or adverse neonatal events did not differ significantly between groups.
Conclusions:
Discontinuing aspirin at 24−28 weeks of gestation was noninferior to continuing aspirin until 36 weeks of gestation for preventing preterm eclampsia in individuals with a high first trimester risk of preeclampsia and a normal sFlt:PlGF ratio. Early discontinuation may decrease the risk of minor bleeding complications or pregnancy complications at ≥37 weeks’ gestation.
Perspective:
This study provides novel data on the best time to discontinue aspirin in patients with high first trimester risk of preeclampsia and low sFlt-1:PlGF ratio (suggesting low risk of preterm preeclampsia). In addition, these patients were on one of the higher recommended aspirin doses (150 mg/day), which may explain the difference in bleeding outcomes observed. This study was not powered for more rare bleeding outcomes, though notably the study was stopped early due to higher incidence of placental abruption in the control group at the interim analysis (1.1% vs. 0; p = 0.12), which was considered clinically significant. Furthermore, larger analyses will be needed to better define the optimal time to discontinue aspirin to decrease the risk of those rare complications at <34 weeks’ gestation and other bleeding complications.
Clinical Topics: Cardiovascular Care Team, Congenital Heart Disease and Pediatric Cardiology, Prevention, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, Hypertension
Keywords: Aspirin, Eclampsia, Fetus, Gestational Age, Hemorrhage, Hypertension, Infant, Newborn, Patient Care Team, Placenta Growth Factor, Pre-Eclampsia, Pregnancy, Pregnancy Complications, Primary Prevention, Women
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