Preeclampsia prevention improved by 150 mg aspirin vs 75 mg

Preeclampsia prevention improved by 150 mg aspirin vs 75 mg | Image Credit: © ironstealth - © ironstealth - stock.adobe.com.

A daily 150 mg dose of aspirin is more effective at inhibiting thromboxane B2 (TbxB2) compared to a 75 mg dose, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Aspirin use in pregnant women

Experts recommend pregnant women with an increased preeclampsia (PE) risk receive prophylactic low-dose aspirin, with the recommended dose varying from 75 to 150 mg/d. Recent data has supported the use of higher doses vs lower doses, more effectively preventing PE with severe features among individuals with obesity.²

“However, as new studies continue to compare the clinical effectiveness of different aspirin doses, there remains a lack of understanding regarding the differences in pharmacokinetic and pharmacodynamic parameters of commonly used doses aspirin in this patient cohort,” wrote investigators.¹

Pharmacokinetic and pharmacodynamic evaluation

The single site randomized crossover study was conducted to evaluate the pharmacokinetics and pharmacodynamics of 75 mg vs 150 mg aspirin in pregnant patients with increased PE risk. Participants were assigned to one of these treatment options through randomization using Sealed Envelope software.

Groups included a 75 mg followed by 150 mg sequence group and a 150 mg followed by 75 mg sequence group. A 1-week washout period occurred between 75 mg and 150 mg doses, with participants taking 75 mg tablets either once or twice per day depending on their current dosage.

Baseline TbxB2 and salicylic acid (SA) were measured from the antecubital fossa using an intravenous cannula. Investigators also collected patients’ blood samples at 1, 2, 3, and 4 hours post-aspirin ingestion. The next day, additional samples were collected at 15, 16, 17, 18, and 19 hours post-ingestion.

The trapezoidal method was used to measure areas under serum SA concentration vs time curve (AUC). Pharmokinetic models were based on extravascular administration with a first order absorption (rate constant ka) and an associated lag time.

Pharmacokinetics and TbxB2 inhibition

There were 14 participants included in the final analysis, none of whom reported adverse events during the trial. In aspirin naïve participants, SA serum concentrations at baseline varied between 0.004 μg/ml and 0.016 μg/ml, indicating residual concentrations from patients’ diets. These concentrations did not differ between dose sequences.

A higher serum SA maximum concentration (Cmax) and AUC were noted following the 150 mg dose vs the 75 mg dose, with median Cmax of 3.03 μg/ml and 1.56 μg/ml, respectively, and median AUCs of 16.68 μg ∗h/ml and 6.8 μg ∗h/ml, respectively. Both aspirin doses led to higher serum SA concentrations at 15, 16, 17, 18, and 19 hours post-administration.

Baseline serum TbxB2 concentrations did not significantly differ between groups, ranging from 0.49 ng/ml to 118.08 ng/ml. However, serum TbxB2 concentrations rapidly declined following the administration of either a 75 mg dose or a 150 mg dose. The 150 mg dose led to a larger reduction, with a mean of 95.4% in the 150 mg group vs 79.1% in the 75 mg group over 19 hours.

Advantages of a 150 mg dose

Eighty-six percent of women taking the 75 mg dose achieved a maximum reduction of over 90% in serum TbxB2, vs every patient taking the 150 mg dose. Overall reductions were also greater in the 150 mg group vs the 75 mg group, at 95.67% vs 84.76%, respectively.

These results indicated improved efficacy of a 150 mg of aspirin toward inhibiting TbxB2 concentrations vs a 75 mg dose. Investigators recommended further research about the impact of higher aspirin doses for PE prevention.

“Despite limitations, measuring serum SA concentration could still be used in future models to test adherence if done within 12 hours after ingestion,” wrote investigators.

References

1. Vinogradov R, Kavanagh ON, Palmer J, et al. A randomized crossover design study comparing the pharmacokinetics and pharmacodynamics of 2 single doses of oral aspirin (75 mg v 150 mg) in pregnant women at risk of preeclampsia: implications on assessing aspirin response and patient adherence to therapy. Am J Obstet Gynecol. 2025;232:474.e1-15. doi:10.1016/j.ajog.2024.10.023
2. Amro FH, Blackwell SC, Pedroza C. Aspirin 162 mg vs 81 mg for preeclampsia prophylaxis in high-risk obese individuals: a comparative effectiveness open-label randomized trial (ASPREO). Am J Obstet Gynecol. 2025;232(3):315.e1-315.e8. doi:10.1016/j.ajog.2024.06.038