Daily Aspirin Dosing for Preeclampsia Prevention

Is a 162-mg dose of daily aspirin more effective than an 81-mg dose in preventing preeclampsia in pregnant patients at risk?

In pregnant patients at high risk for preeclampsia, daily aspirin at any dose reduces the risk. (Strength of Recommendation [SOR]: B, systematic review and meta-analysis of randomized controlled trials [RCTs].) In comparing daily aspirin 75 to 81 mg with 150 to 161 mg for prevention of preterm preeclampsia, higher doses result in lower rates of preterm preeclampsia but not lower rates of preeclampsia at any gestational age. Individual RCTs evaluating doses of aspirin have contradictory results. Current evidence does not support recommending daily aspirin at doses higher than 81 mg for preeclampsia prevention. (SOR: B, two open-label RCTs.)

A 2021 systematic review and meta-analysis of 23 RCTs (N = 32,270) evaluated daily aspirin for preeclampsia prevention in pregnant patients ages 15 to 55 years with moderate to high risk factors. One of the 23 articles was used only in preterm preeclampsia analysis. Aspirin doses were categorized as 36 to 80 mg (14 studies), 81 mg (one study), 100 mg (six studies), and 150 mg (one study), with most trials starting treatment before 16 weeks' gestation. The primary outcomes were the effect of aspirin doses on rates of preeclampsia at any gestational age and preterm preeclampsia.¹

Across all doses, aspirin reduced preeclampsia risk by 27% (relative risk [RR] = 0.73; 95% CI, 0.61–0.87). Doses of 81 mg and 100 mg were not associated with a further reduction compared with other doses for preeclampsia prevention at any gestational age (RR = 0.88; 95% CI, 0.21–3.66) and (RR = 0.78; 95% CI, 0.57–1.06), respectively. Doses of 36 to 80 mg and 150 mg showed a reduction of approximately 28% at any gestational age (RR = 0.70; 95% CI, 0.55–0.89 and RR = 0.72; 95% CI, 0.54–0.98, respectively). The number needed to treat was 38 for 36 to 80 mg (additive RR = 2.6; 95% CI, 0.7–4.5) and 31 for 150 mg (additive RR = 3.2; 95% CI, 0.3–6.1).

Only the 150-mg dose of aspirin was shown to reduce the risk of preterm preeclampsia (RR = 0.38; 95% CI, 0.20–0.72; P = .011), with a number needed to treat of 39 (95% CI, 23–100). Several studies had potential sources of bias, including selective reporting and incomplete data, and there was substantial heterogeneity among studies.¹

A 2023 systematic review and meta-analysis of four RCTs (N = 552) compared daily aspirin doses of 75 to 81 mg with doses of 150 to 162 mg for prevention of preterm preeclampsia. Included studies evaluated aspirin doses initiated before 16 weeks' gestation and followed patients through delivery. Studies were excluded if aspirin was initiated after 16 weeks' gestation or before pregnancy, or if aspirin was used for reasons other than preeclampsia prevention.²

In the three RCTs (n = 472) that evaluated aspirin dosing for prevention of preterm preeclampsia, higher doses of aspirin resulted in a significant reduction (RR = 0.34; 95% CI, 0.15–0.79). In the one RCT that evaluated aspirin dosing for preeclampsia prevention at any gestational age, higher doses of aspirin did not show a risk reduction (n = 552; RR = 0.42; 95% CI, 0.17–1.05). The study outcome for any preeclampsia was at high risk of bias due to deviation from the intended interventions, selection of the reported results, and randomization. Two studies were at risk of bias due to the randomization process.²