Low-dose aspirin for preeclampsia prevention: efficacy by ethnicity and race

Background: Low-dose aspirin is recommended for the prevention of preeclampsia among women at a high risk of developing the disease. Aspirin undergoes polymorphic metabolism, and it is well known that common genetic polymorphisms are related to aspirin intolerance. We hypothesized that the efficacy of aspirin prophylaxis may differ by ethnicity and race.

Objective: This study aimed to compare the rates of preeclampsia among low- and high-risk women who received aspirin compared with placebo, stratifying results by ethnicity and race as a first-pass approximation of genomic polymorphisms.

Study design: This is a secondary analysis of 2 randomized controlled trials previously performed by the Maternal-Fetal Medicine Units Network: the Low-Risk Aspirin trial and the High-Risk Aspirin trial. For the Low-Risk Aspirin trial, normotensive, nulliparous women were enrolled between 13 and 26 weeks' gestation and randomized to 60 mg aspirin daily or placebo. For the High-Risk Aspirin trial, women with pregestational insulin-treated diabetes mellitus, chronic hypertension, multiple gestations, or a history of preeclampsia in a previous pregnancy were enrolled between 13 and 26 weeks' gestation and randomized to 60 mg aspirin daily or placebo. The primary outcome of our secondary analysis was preeclampsia. Secondary outcomes included gestational age at delivery, preterm delivery, placental abruption, small for gestational age, stillbirth, and neonatal death. Outcomes were stratified by ethnicity and race (Hispanic, non-Hispanic white, non-Hispanic black, or other).

Results: In the Low-Risk Aspirin trial of 3135 women, the risk of preeclampsia was significantly reduced among non-Hispanic white women who received aspirin compared with non-Hispanic white women who received placebo (relative risk, 0.19; 95% confidence interval, 0.06-0.63; P=.007). The risk of preeclampsia was not different when comparing the aspirin and placebo groups among the Hispanic, non-Hispanic black, or other ethnicity and race groups. The efficacy among non-Hispanic white women persisted after consideration of compliance and gestational age at randomization (relative risk, 0.07; 95% confidence interval, 0.009-0.51; P=.009). As noted in the original trial, there was an increased risk of placental abruption in the aspirin group overall compared with placebo (P=.025). The risk of stillbirth was significantly increased among non-Hispanic black women who received aspirin compared with non-Hispanic black women who received placebo (P=.048). In the High-Risk Aspirin trial of 2539 women, 269 were Hispanic (10.6%), 832 were non-Hispanic white (32.8%), 1426 were non-Hispanic black (56.2%), and 12 were categorized as other (0.5%). Stratification by ethnicity and race did not reveal a decreased incidence of preeclampsia for any of the subgroups (P>.05). Moreover, there was no significant difference in other measured outcomes including preterm delivery at <37 weeks' gestation, placental abruption, small for gestational age, stillbirth, or neonatal death.

Conclusion: The incidence of preeclampsia was significantly reduced among low-risk non-Hispanic white women who received aspirin compared with placebo (P=.007), but not overall or among Hispanic or non-Hispanic black women. The analysis of high-risk women did not indicate a difference in the efficacy of aspirin by ethnicity and race.