Network meta-analysis: comparative efficacy of diverse aspirin dosages and heparin in mitigating placenta-mediated pregnancy complications

This study aimed to assess the comparative efficacy of different low-dose aspirin (ASA) dosages, either alone or in combination with heparin, in preventing placenta-mediated pregnancy complications (PMPC) among high-risk pregnant women using a network meta-analysis (NMA). PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for randomized controlled trials (RCTs) up to August 15, 2025. Studies evaluating ASA (< 100 mg/day, ≥ 100 mg/day), unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and their combinations in high-risk populations were included. Data from 63 RCTs (20,325 participants) were analyzed using Bayesian random-effects NMAs and trial sequential analysis (TSA). All anticoagulant regimens significantly reduced preeclampsia (PE) risk by 24–95% compared to placebo/no treatment. The combination of < 100 mg/day ASA + LMWH notably decreased severe PE (odds ratio [OR] = 0.05, 95% confidence interval [CI] = 0.00–0.59) and miscarriage and stillbirth or perinatal death (OR = 0.50, 95% CI = 0.32–0.77). TSA confirmed that ≥ 100 mg/day ASA + LMWH significantly reduced PMPC risk. While LMWH alone showed efficacy in reducing placental abruption, combined regimens outperformed monotherapies in overall PMPC prevention. No significant differences in bleeding risk or neonatal outcomes (e.g., preterm delivery) were observed across regimens. Anticoagulant therapies, particularly combinations of ASA and LMWH, effectively mitigate PMPC. The < 100 mg/day ASA + LMWH regimen demonstrates optimal efficacy in reducing severe PE and fetal loss, while ≥ 100 mg/day ASA + LMWH is strongly supported by TSA. These findings inform clinical decisions for PMPC prophylaxis. What are the differences in the associations between PMPC-related adverse outcomes and eight routine anticoagulant therapies for PMPC in high-risk patients? In this network meta-analysis of 63 randomized controlled trials (RCTs) involving over 20,325 patients, the combination of < 100 mg/day ASA + LMWH significantly reduced the occurrence of severe PE (odds ratio [OR], 0.05 [95% confidence interval (CI), 0.00–0.59]) and miscarriage and stillbirth or perinatal death (OR, 0.50 [95% CI, 0.32–0.77]) compared with placebo/no therapy. It also reduced the risk of placental abruption and fetal growth restriction/small for gestational age (FGR/SGA) compared with LMWH (odds ratio, 0.49 [0.27–0.88]) and ≥ 100 mg/day ASA + LMWH (odds ratio, 0.43 [0.21–0.89]). Trial sequential analysis (TSA) indicated that ≥ 100 mg/day ASA + LMWH significantly decreased PMPC risk relative to placebo/no intervention, providing robust evidence for its clinical application due to the sufficient sample size and low random error. The findings of this meta-analysis offer insights into routine anticoagulant medications and PMPC-related adverse outcomes, which can guide clinical decision-making regarding PMPC prevention.