Stick With Baby Aspirin in Patients at High Risk for Preeclampsia

AURORA, Colo. — A higher dose of aspirin offered no significant benefit as preeclampsia prevention in high-risk patients, although those with multifetal gestations may have seen some gains, according to the ASAPP trial.

The study tested 162 mg of aspirin compared with 81-mg daily, and found that there was no significant difference in rates of preterm preeclampsia or preeclampsia with severe features between the two groups at 13% for 162-mg and 14% for 81-mg (P=0.7), reported Amrin Khander, MD, of Weill Cornell Medical College in New York City, at the Society for Maternal-Fetal Medicine annual meeting.

In subgroup analyses, the higher dose of aspirin achieved statistical significance, but not clinical significance, in patients with multifetal gestations (OR 0.2, 95% CI 0.0-0.9) for being protective against preeclampsia. But the study was not powered to subgroups so the findings are exploratory.

Patients in the 162-mg group were statistically more likely to experience an adverse event, characterized as an unscheduled interaction with the healthcare system (21% vs 12% in the 81-mg group, P=0.02). Among singleton pregnancies, those in the 162-mg group delivered slightly earlier (37.71 weeks vs 38.14 weeks, respectively, P=0.05) and infants had slightly lower birthweight (2.9 kg vs 3.2 kg, P=0.002). But none of the data were clinically significant, Khander said.

She explained that low-dose or “baby” aspirin is the only recognized prophylaxis for preeclampsia. Past research has shown that low-dose aspirin doesn’t impact the kids’ brain development.

Previous trials have used a wide range of doses, from 60-150 mg daily. In terms of prophylaxis for people at high risk of preeclampsia, “existing literature suggests that higher aspirin doses may be more protective, but prospective data directly comparing low and high doses are lacking,” Khander said.

Amanda Roman, MD, MPH, of Thomas Jefferson University in Philadelphia, said the finding about multifetal gestations was promising and that monitoring adherence was a study strength. The authors reported that starting at 18 weeks, and up to 38 weeks, adherence rates ranged from 88%-91% for 162-mg aspirin, and 89%-92% for 81-mg aspirin.

However, it would be more helpful to test aspirin dosing related to preterm severe preeclampsia, “which is where you see severe fetal outcomes, but… you need a very large sample size,” she told MedPage Today.

Roman also noted that past data have shown that patients see the best results starting aspirin between 6-12 weeks — much earlier than this trial initiated treatment — because the placenta develops early, noted Roman, who was not involved in the current study. The latter would benefit from reporting results stratified by BMI, she added.

ASAPP took place from January 2020-August 2023 at New York Presbyterian-Weill Cornell Manhattan and Queens campuses. After the first 100 patients delivered, they conducted a prespecified interim analysis to determine feasibility and final sample size.

A total of 400 patients were randomized 1:1 to either 81-mg or 162-mg per day; 186 were analyzed in the 162-mg group and 183 in the 81-mg group after loss to follow-up and pregnancy loss. Baseline age for both groups was 35; 41% of the 162-mg group were white as were 32% of the 81-mg group. The former had 15% Asian patients while the latter had 22%. The higher-dose group had 19% Black/African-American patients while the latter had 23%. A chronic hypertension diagnosis was present in 41% of the 162-mg group and 33% of the 81-mg group. A history of preeclampsia was seen in 35% and 34%, respectively.

Patients began therapy at the baseline visit less than 16 weeks gestation and were instructed to continue taking aspirin through delivery, unless otherwise directed by their ob/gyn. Patients were evaluated between 18-22 weeks, 24-28 weeks, and 34-38 weeks; data after then came from chart review. Investigators were blinded to treatment.

Incidence of preterm preeclampsia at less than 37 weeks’ gestation or term preeclampsia with severe features was the primary outcome. Secondary outcomes included adherence to the aspirin regimen, determined by a validated questionnaire, as well as maternal and neonatal outcomes, including spontaneous pregnancy loss, gestational age at delivery, blood loss at delivery, blood transfusion rates, maternal ICU admission, neonatal ICU admission, and length of stay at either.

Eligible participants were pregnant people at high risk for preterm preeclampsia as defined by the American College of Obstetricians and Gynecologists, as having one or more of the following:

• Chronic hypertension
• History of preterm preeclampsia
• Diabetes mellitus
• Autoimmune disease
• Multifetal gestation
• Kidney disease

Exclusion criteria included known intention to terminate the pregnancy, major fetal malformations seen on an ultrasound between 11-13 weeks, plans to deliver outside the hospital system, contraindication to aspirin, and the primary ob/gyn declining patient participation.

Study limitations included the open-label design; the geographical proximity of the two institutions; the fact that most participants had commercial insurance (72%-74%). Also, patients who could give written consent in English were excluded.

Khander noted future research should replicate the trial with larger cohorts in multicenter, geographically diverse areas. Further research also is needed on the optimal time to start and discontinue aspirin in pregnancy, she said.

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