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.
Mak
Anselm
A
Department of Medicine, Division of Rheumatology, University Medical Cluster, National University Health System, Yong Loo Lin School of Medicine, Singapore. mdcam@nus.edu.sg
Cheung
Mike W-L
MW
Cheak
Alicia Ai-cia
AA
Ho
Roger Chun-Man
RC
D000026:Abortion, Habitual / Q000276:immunology / Q000517:prevention & control*; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood; D000925:Anticoagulants / Q000627:therapeutic use; D016736:Antiphospholipid Syndrome / Q000188:drug therapy*; D001241:Aspirin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D050498:Live Birth; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000276:immunology; D016032:Randomized Controlled Trials as Topic
D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D001241:Aspirin