TY - JOUR
T1 - Antithrombotic therapy to prevent recurrent pregnancy loss in antiphospholipid syndrome—What is the evidence?
AU - Hamulyák, Eva N.
AU - Scheres, Luuk J. J.
AU - Goddijn, Mariëtte
AU - Middeldorp, Saskia
N1 - Funding Information: S. Middeldorp reports grants and fees paid to her institution from GSK, BMS/Pfizer, Aspen, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Sanofi, and Portola. L.J.J. Scheres received funding for the printing of his doctoral thesis from the Dutch Heart Foundation, Dutch Federation of Coagulation Clinics, Stichting tot Steun Promovendi Vasculaire Geneeskunde, Bayer, Daiichi Sankyo, LEO Pharma, and Pfizer, outside the submitted work. M. Goddijn works at the Department of Reproductive Medicine of the Amsterdam UMC (location AMC and location VUmc). Location VUMC has received several research and educational grants from Guerbet, Merck, and Ferring, not related to the presented work. E.N. Hamulyák has nothing to disclose. Funding Information: The authors would like to thank Mauritia Marijnen for her help in the data preparation and Lynn Hampson, Jim Neilson, Emily Shepherd, Fiona Stewart, and Frances Kellie of the Cochrane Pregnancy and Childbirth Trials Register for their guidance in constructing and finalizing this review. L.J.J. Scheres was a PhD candidate of the CREW project (2013T083) supported by the Netherlands Heart Foundation. S. Middeldorp was supported by a VIDI grant for the Netherlands Organization for Health Research and Development (0.16.126.364). This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to Cochrane Pregnancy and Childbirth. Publisher Copyright: © 2021 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis
PY - 2021/5
Y1 - 2021/5
N2 - Aspirin and heparin are widely used to reduce the risk of recurrent pregnancy loss in women with antiphospholipid syndrome. This practice is based on only a few intervention studies, and uncertainty regarding benefits and risk remains. In this case-based review, we summarize the available evidence and address the questions that are most important for clinical practice. We performed a systematic review of randomized controlled trials assessing the effect of heparin (low molecular weight heparin [LMWH] or unfractionated heparin [UFH]), aspirin, or both on live birth rates in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Eleven trials including 1672 women met the inclusion criteria. Aspirin only did not increase live birth rate compared to placebo in one trial of 40 women (risk ratio [RR] 0.94; 95% confidence interval [CI] 0.71–1.25). One trial of 141 women reported a higher live birth rate with LMWH only than with aspirin only (RR 1.20; 95% CI 1.00–1.43). Five trials totaling 1295 women compared heparin plus aspirin with aspirin only. The pooled RR for live birth was 1.27 (95% CI 1.09–1.49) in favor of heparin plus aspirin. There was significant heterogeneity between the subgroups of LMWH and UFH (RR for LWMH plus aspirin versus aspirin 1.20, 95% CI: 1.04–1.38; RR for UFH plus aspirin versus aspirin 1.74, 95% CI: 1.28–2.35; I2 78.9%, p =.03). Characteristics of participants and adverse events were not uniformly reported. Heparin (LMWH or UFH) plus aspirin may improve live birth rates in women with recurrent pregnancy loss and antiphospholipid antibodies, but evidence is of low certainty.
AB - Aspirin and heparin are widely used to reduce the risk of recurrent pregnancy loss in women with antiphospholipid syndrome. This practice is based on only a few intervention studies, and uncertainty regarding benefits and risk remains. In this case-based review, we summarize the available evidence and address the questions that are most important for clinical practice. We performed a systematic review of randomized controlled trials assessing the effect of heparin (low molecular weight heparin [LMWH] or unfractionated heparin [UFH]), aspirin, or both on live birth rates in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Eleven trials including 1672 women met the inclusion criteria. Aspirin only did not increase live birth rate compared to placebo in one trial of 40 women (risk ratio [RR] 0.94; 95% confidence interval [CI] 0.71–1.25). One trial of 141 women reported a higher live birth rate with LMWH only than with aspirin only (RR 1.20; 95% CI 1.00–1.43). Five trials totaling 1295 women compared heparin plus aspirin with aspirin only. The pooled RR for live birth was 1.27 (95% CI 1.09–1.49) in favor of heparin plus aspirin. There was significant heterogeneity between the subgroups of LMWH and UFH (RR for LWMH plus aspirin versus aspirin 1.20, 95% CI: 1.04–1.38; RR for UFH plus aspirin versus aspirin 1.74, 95% CI: 1.28–2.35; I2 78.9%, p =.03). Characteristics of participants and adverse events were not uniformly reported. Heparin (LMWH or UFH) plus aspirin may improve live birth rates in women with recurrent pregnancy loss and antiphospholipid antibodies, but evidence is of low certainty.
KW - antiphospholipid syndrome
KW - heparin
KW - live birth
KW - recurrent pregnancy loss—aspirin
UR - http://www.scopus.com/inward/record.url?scp=85103154976&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/jth.15290
DO - https://doi.org/10.1111/jth.15290
M3 - Article
C2 - 33687789
SN - 1538-7933
VL - 19
SP - 1174
EP - 1185
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 5
ER -