Aspirin Plus Heparin May Prevent Recurrent Miscarriage in Women With Antiphospholipid Syndrome

Researchers compared and evaluated pharmacologic interventions for the prevention of recurrent miscarriage in women with antiphospholipid syndrome.

Low-dose aspirin plus heparin may be considered as a first-line treatment for the prevention of recurrent miscarriage in women with antiphospholipid syndrome (APS), according to research results published in Lupus. The other supported additions to current treatment regimens include hydroxychloroquine, prednisone, and intravenous immunoglobulin (IVIG). 

To investigate the prevention of recurring miscarriage in pregnant women with antiphospholipid syndrome, the study authors sourced research databases including PubMed, Cochrane, and Embase. All selected studies included comparisons of active interventions with placebo or another type of active intervention. Primary outcomes of the analysis included efficacy (assessed by the rate of live births) and acceptability (assessed by the withdrawal rates of participants). Statistical analysis were performed on the primary outcomes using pairwise meta-analyses, with Cochrane’s Q test and the I2 statistic to assess heterogeneity among the selected studies.

The current network meta-analysis included 54 randomized controlled trials conducted from 1991 to 2019, which included 4957 participants (n=4520 were randomly assigned to receive active intervention; n=437 to placebo).

Treatments found to be significantly more effective than placebo included low-molecular-weight heparin (LMWH) alone (odds ratio [OR], 3.94; 95% CI, 1.68-9.87), aspirin plus LMWH (OR, 2.88; 95% CI, 1.73-4.95), aspirin plus unfractionated heparin (OR, 3.82; 95% CI 1.90-7.69), aspirin plus IVIG plus LMWH (OR, 6.05; 95% CI, 1.69-21.76), and aspirin plus IVIG plus LMWH plus prednisone (OR, 11.24; 95% CI, 3.12-51.42). According to the study authors, the treatments showed no significant difference in terms of acceptability. Compared to aspirin plus LMWH, aspirin alone correlated with a greater risk for premature birth (OR, 3.92; 95% CI, 1.16-16.44), and with lower birthweight than LMWH alone (standardized mean difference, -808.76; 95% CI, -1596.54 to -5.07).

The highest-ranked treatment in this study was aspirin plus LMWH plus IVIG plus prednisone, followed by aspirin plus LMWH plus IVIG, and LMWH alone. Study authors also noted that, due to the “need to improve obstetric outcomes in some patients after receiving current standard of treatments,” further robust randomized controlled trials are needed.

Study limitations included randomization at 8 to 12 weeks of pregnancy in certain studies, though research has shown that fetal cardiac activity at 7 weeks correlates strongly with successful birth, the higher complication rate of prednisone, potential publication bias due to a lack of available high-quality studies published after 2010, heterogeneity in obstetric recording, and a high risk for bias and imprecision in the majority of outcomes.

Study researchers concluded that evidence supports the use of low-dose aspirin plus UFH as a “first-line treatment for women with [recurrent miscarriage] associated with APS.” In addition, “the results support the efficacy of [hydroxychloroquine], IVIG, and prednisone when added to current treatment regimens.”


Yang Z, Shen X, Zhou C, Wang M, Liu Y, Zhou L. Prevention of recurrent miscarriage in women with antiphospholipid syndrome: a systematic review and network meta-analysis. Lupus. Published online October 20, 2020. doi:10.1177/0961203320967097