Impacto combinado del riesgo en el primer trimestre y la adherencia a la aspirina en la prevención de la preeclampsia...

Aspirin prevents preterm pre-eclampsia (PE) in high-risk pregnancies, but the extent to which its effectiveness depends on adherence and baseline risk remains uncertain.

To evaluate how first-trimester PE risk and aspirin adherence jointly influence aspirin's preventive effect, and to assess the potential benefits and harms of targeted versus universal prophylaxis.

We combined data from the Aspirin for Evidence-based Preeclampsia Prevention (ASPRE) and the Screening Program for Preeclampsia (SPREE) cohorts, including singleton pregnancies delivering at ≥24 weeks. All pregnancies were screened for preterm PE at 11⁺⁰ to 13⁺⁶ weeks using the Fetal Medicine Foundation (FMF) competing risks model, which combines maternal characteristics, mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor. Aspirin adherence and baseline risk distributions were modeled using Monte Carlo simulations to estimate relative risk (RR), absolute risk reduction (ARR), and number needed to treat (NNT) under four adherence scenarios: full (100%), trial-based (intention-to-treat), 50%, and variable adherence positively correlated with predicted risk (ρ=0.4). Decision-curve analysis assessed net benefit across risk thresholds.

Simulations informed by 51,024 pregnancies indicated that aspirin's preventive effect varied substantially with adherence. In fixed-adherence scenarios, the strongest effect occurred with full adherence (RR 0.25, 95% CI 0.09-0.66) and the weakest with 50% adherence (RR 0.70, 95% CI 0.58-0.98). Under variable adherence, RR decreased non-linearly with baseline risk, approaching the per-protocol effect in high-risk women but near null in low-risk women. ARR and NNT were highly dependent on predicted risk: at 1 in 50 to 1 in 100 risks, NNT ranged from 73 to 146 with high adherence and 161 to 321 with 50% adherence, whereas at lower risks, NNTs exceeded several thousand even with high adherence. Decision-curve analysis indicated that targeted prophylaxis using the FMF model provided greater net benefit than universal treatment, primarily by avoiding unnecessary interventions.

Aspirin is highly effective for preventing preterm PE in women at increased risk, but its effect depends on predicted risk and adherence. The absolute benefit of treatment is negligible in low-risk populations. A targeted screen-and-treat strategy using the FMF model maximizes clinical benefit while minimizing unnecessary treatment.