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LMWH did not reduce complications in pregnant women with thrombophilia
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Low–molecular-weight heparin did not reduce risk for venous thromboembolism, pregnancy loss or placenta-mediated pregnancy complications in women with thrombophilia at high risk for those complications, according to study results.
“These results mean that many women around the world can save themselves a lot of unnecessary pain during pregnancy,” Marc Rodger, MD, FRCPC, MSc, senior scientist at Ottawa Hospital Research Institute, said in a press release. “Using low–molecular-weight heparin unnecessarily medicalizes a woman’s pregnancy and is costly.”
Rodger and colleagues sought to evaluate the effects of anticoagulation with dalteparin (Fragmin, Eisai), a form of low–molecular-weight heparin (LMWH). Dalteparin had been the preferred thromboprophylactic agent during pregnancy because it does not cross the placenta and has a favorable safety profile, according to background information provided by the researchers.
The analysis included 143 women who received the antepartum prophylactic dose of 5,000 international units of dalteparin daily until 20 weeks of gestation, followed by twice-daily doses until 37 weeks of gestation. An additional 141 women included in the control arm received no dalteparin.
The mean age of patients was 31.8 years, and the mean gestational age at the time of randomization was 11.9 weeks. The mean number of previous pregnancies in the cohort was 2.2 and the mean number of previous deliveries was 1. Most of the study population (61%) had experienced complications during a prior pregnancy.
The primary composite outcome included adjudicated severe or early-onset pre-eclampsia, small-for-gestational-age infant, pregnancy loss and venous thromboembolism (VTE).
Results of the intention-to-treat analysis indicated dalteparin did not reduce the occurrence of one or more components of the composite endpoint. Incidence was 17.1% in the treatment group vs. 18.9% in the control group (risk difference, –1.8%; 95% CI, –10.6 to 7.1). The on-treatment analysis also indicated the composite endpoint was comparable among women who did and did not receive dalteparin (19.6% vs. 17%; risk difference, 2.6%; 95% CI, –6.4 to 11.6).
The incidence of major bleeding events was similar between study arms. However, 19.6% of women who received dalteparin experienced minor bleeding compared with 9.2% of women in the control arm (risk difference, 10.4%; 95% CI, 2.3-18.4).
“These findings allow us to move on, to pursue other potentially effective methods for treating pregnant women with thrombophilia and/or complications from placenta blood clots,” Rodger said.
The study took 12 years to accrue due to the fact that some centers already used LMWH as standard practice in this setting, Paul S. Gibson, MD, of the University of Calgary and Kara A. Nerenberg, MD, of the Royal Alexandra Hospital at the University of Alberta, wrote in an accompanying editorial.
“This situation draws attention to the fact that clinicians’ altruistic intentions to treat those high-risk women might have inadvertently caused them minor harm, potentially increased rates of labor induction, reduced access to regional anesthetics, increased health care costs (because of the high cost of low–molecular-weight heparin), and slowed the research momentum in this area,” Gibson and Nerenberg wrote. “Hopefully, these results will finally tip clinicians away from using the drug in this setting and motivate researchers to pursue other potentially effective preventive interventions.”
For more information:
- Gibson PS. Lancet. 2014;doi:S0140-6736(14)60850-3.
- Rodger MA. Lancet. 2014;doi:S0140-6736(14)60793-5.
Disclosure: One researcher reports honoraria from Bayer, Leo Pharma and Sanofi. Gibson reports an unrestricted educational grant from Sanofi.