Aspirin in combination with heparin results in more live births in Repeated Pregnancy Loss: a systemic review and meta-analysis

Aspirin in combination with heparin ups the odds of live births 2.5 times as compared to aspirin alone among women with antiphospholipid syndrome (APS) who had experienced repeated pregnancy loss says the result of a systematic review and meta-analysis.

The prevalence of APS in women with RPL varies according to studies, from as low as 6% to as high as 42%, but it is generally accepted to be 5%–20%.

The results were presented at the International Society on Thrombosis and Haemostasis (ISTH)2017 Conference.

Researchers at Leiden University Medical Center in the Netherlands conducted a systematic literature search for randomized controlled trials that compared low dose aspirin (LDA), low-molecular-weight heparin (LMWH)or unfractionated heparin (UFH), or both on the effect of live birth in women with APS and recurrent pregnancy loss.

The study is an update of earlier Cochrane Database Systematic Review by Empson andcolleagues from 2005.

The investigators identified 939 research studies, full text review resulted in 9 studies, of which only 5 were included in the final analysis. Combined data resulted in a total of 398 women. Studies were excluded if they did not meet the diagnostic criteria   for APS.

The study results showed that:

LDA alone did not have much potential benefits in increasing the live birth rates as compared to a placebo.

Heparin of any kind resulted in live birth rate 2.5 times that of LDA alone (odds ratio [OR] 2.51; 95% CI 1.48–4.25, P<0.001).

When unfractionated heparin (UFH) was combined with LDA the likelihood of live birth rates increased to 3.75 times as compared to LDA alone in an analysis of pooled data from three studies. (odds ratio [OR] 3.75; 95% CI 2.04–6.90, P<0.001).

However, when LMWH was paired with LDA in two studies, there was no significant difference in odds of having a live birth.

This systematic review and meta-analysis findings were limited by sample size, lack of adverse effects reporting of heparin and aspirin in the original studies, dose disparities. Mauritia Marijnen from Academic Medical Center, Amsterdam, the Netherlands stressed on urgent need of rigorous randomized controlled trials, particularly on the use of LMWH.

Unfractionated heparin (UFH) is an older drug with side effects, but in this meta-analysis it appeared to be more effective in increasing the odds of live birth rates. It maybe because of some other confounders which were not analyzed in this study, which makes it all the more important to carry out future studies with LMWH.

The authors concluded, “Heparin plus aspirin compared with aspirin improves live birth in women with APS and recurrent pregnancy loss. This effect is driven by studies that investigated UFH and not LMWH.”

All the abstract presented at the conference can be accessed here.

Primary source: Marijnen MC, Scheres LJJ, Middeldorp S, et al. Aspirin, heparin or both to improve live birth in women with antiphospholipid syndrome and recurrent pregnancy loss. ISTH 2017; July 11, 2017; Berlin, Germany. Abstract ASY 22.3.