Doubling up on the daily aspirin dose of 81 mg appears to yield no significant protective effect against the incidence of preeclampsia in high-risk pregnancies, suggests findings from the ASAPP* study presented at SMFM 2025.

“Our data show that the rates of preterm preeclampsia or preeclampsia with severe features were similar in pregnant women at high risk for preeclampsia taking aspirin 81 mg or 162 mg,” said the researchers, led by presenting author Dr Amrin Khander from the Weill Cornell Medicine/New York ? Presbyterian Hospital, New York, New York, US.

The rates of the primary composite outcome of preterm preeclampsia or preeclampsia with severe features were 14 percent with the 81-mg dose and 13 percent with the 162-mg dose. A comparison between arms yielded a p value of 0.7. [SMFM 2025, abstract LB06]

Adherence rates based on the Simplified Medication Adherence Questionnaire scores were also similar between study arms irrespective of gestational timepoints (ranging between 88 percent and 92 percent).

On subgroup analyses, the incidence of the primary outcome was lower in the 162- vs 81-mg arm in women with multifoetal gestation (4 percent vs 21 percent; odds ratio, 0.2; p=0.08). “Given the physiologic increased placental volume in multifoetal gestations or development of two placentas in dichorionic pregnancies, a higher aspirin dose in this population makes sense,” explained Khander.

However, the difference between arms were not considered clinically significant, Khander noted. Rather, the results were deemed exploratory, thus warranting further studies for validation.

Moreover, the 162-mg arm had lower infant birthweight (2.9 vs 3.2 kg; p=0.01), greater quantitative blood loss at delivery (705 vs 552 mL; p=0.5), slightly earlier deliveries (37.7 vs 38.1 weeks; p=0.05), and more neonatal intensive care unit admissions (16 percent vs 9.3 percent; p=0.06) than the low-dose arm, but none of the between-group differences were clinically significant.

The overall incidence of adverse events was nearly twofold higher in the 162- vs 81-mg arm (21 percent vs 12 percent; p=0.02). “Those on 162 mg were more likely to have bleeding episodes and triage visits for foetal heart rate tracings or elevated blood pressures, but the difference was not significant,” Khander said.

Low-dose aspirin may be sufficient

Khander and colleagues conducted a prospective open-label pragmatic trial involving 369 pregnant women (median age 35 years, 19 percent Asian) at least 16 weeks’ gestation. The participants were randomized 1:1 to either aspirin 81 mg or 162 mg daily and monitored throughout their pregnancy until 6 weeks postpartum.

The American College of Obstetricians and Gynecologists defines high risk for preterm preeclampsia as pregnant women having ≥1 of the following: chronic hypertension, history of preeclampsia, type 1 or type 2 diabetes (T1D or T2D), autoimmune disease, multifoetal gestation, or kidney disease. [https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/12/low-dose-aspirin-use-for-the-prevention-of-preeclampsia-and-related-morbidity-and-mortality, accessed 26 February 2025]

At baseline, over a third of the overall population had chronic hypertension. Similarly, 33 percent had a history of preeclampsia. Nineteen percent had T1D or T2D, 12 percent had autoimmune disease, 16 percent had multifoetal gestation, and 4 percent had kidney disease.

“[E]xisting literature suggests that higher aspirin doses may be more protective, but prospective data directly comparing low and high doses are lacking,” Khander said.

The current findings imply that aspirin 81 mg ? which remains the standard recommended dose and is “the only recognized prophylaxis for preeclampsia” ? may be sufficient for the prevention of preeclampsia in high-risk pregnancies.

Khander recommended further research in larger and geographically diverse populations as the study was only conducted in the New York ? Presbyterian Manhattan and Queens campuses. Future trials should also look into the optimal time to start and stop prophylactic aspirin during pregnancy, she added.