Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression

Objective. The combination of heparin and aspirin was regarded as the 'standard therapy' for patients with recurrent pregnancy loss (RPL) and positive aPL antibodies to enhance live births, but it largely stems from expert opinion. We performed a meta-analysis of randomized controlled trials (RCTs) to assess whether this combination works better than aspirin alone. Methods. RCTs testing the efficacy of a combination of heparin and aspirin vs aspirin alone in patients with RPL and positive aPL antibodies were identified in electronic databases. Random effect meta-analysis was employed to pool relative risks (RRs) (with 95% CI) of live births as the primary outcome. RRs of obstetrical complications and standardized mean difference of birth weight were the secondary outcomes. Mixed-effects meta-regression was performed to identify factors associated with live births. Results. Data from five trials involving 334 patients were analysed. The overall live birth rates were 74.27 and 55.83% in the combination and aspirin alone groups, respectively. Patients who received heparin and aspirin had significantly higher live birth rate (RR 1.301; 95% CI 1.040, 1.629) than aspirin alone, with the number needed to achieve one live birth being 5.6. No significant differences in pre-eclampsia, preterm labour and birth weight were found between both the groups. Meta-regression using age at randomization, previous history of live births and episodes of miscarriages as covariates failed to predict the RR of live birth. Conclusions. The combination of heparin and aspirin is superior to aspirin alone in achieving more live births in patients with positive aPL antibodies and RPL.