Use of blood thinners may be unnecessary in women with recurrent pregnancy loss
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NEW ORLEANS — The use of low-molecular-weight heparin among pregnant women with a history of recurrent miscarriage and inherited thrombophilia had no effect on the live birth rate, results from the phase 3 ALIFE2 trial showed.
Data from the study — presented at ASH Annual Meeting and Exposition — revealed a higher rate of treatment-related adverse events among women who received antithrombotic therapy, leading the investigators to advise against routine use in women with recurrent miscarriages and inherited thrombophilia.
“We hypothesized that due to blood clotting or other effects of thrombophilia, [use of low-molecular-weight heparin] would increase the live birth rate,” Saskia Middeldorp, MD, PhD, professor of vascular medicine at Amsterdam University Medical Center, said during a press briefing. “After adjusting for major baseline characteristics, [results] did not show an increase in live birth rate by intervention with low-molecular-weight heparin.”
Background
The previous ALIFE trial revealed no link between anticoagulant use and prevention of miscarriage in women who experienced recurrent pregnancy loss. However, a subgroup of women in the trial with inherited thrombophilia who took anticoagulants showed a 30% better chance of having a live birth, Middeldorp noted.
Given these results, Middeldorp and colleagues decided to conduct a randomized phase 3 trial to determine whether antithrombotic therapy would influence the live birth rate among women with inherited thrombophilia when compared with standard surveillance.
Methodology
Researchers designed the international, open-label ALIFE2 trial to compare low-molecular-weight heparin with standard pregnancy surveillance in women with inherited thrombophilia and a history of recurrent miscarriage.
The study enrolled women from August 2012 to January 2021 across 15 centers in the Netherlands, U.S., Belgium, Slovenia and U.K. Participants included women aged 18 to 42 actively trying to conceive or less than 7 weeks pregnant. Other eligibility criteria included at least two previous miscarriages and confirmed inherited thrombophilia.
The investigators randomly assigned 326 women (mean age, 33 years; 83% white) in a 1:1 ratio to receive subcutaneous low-molecular-weight heparin (n = 164) once daily or undergo standard pregnancy surveillance (n = 162) after confirmation of their pregnancy.
Approximately 70% of study participants had three or more previous miscarriages.
The live birth rate served as the study’s primary outcome measurement. Secondary measurements included adverse pregnancy outcomes, congenital malformations and safety.
Key findings
Results showed a live birth rate of 71.6% among women who receive low-molecular-weight heparin compared with 70.9% in the standard surveillance group (adjusted OR = 1.08; 95% CI, 0.65-1.78).
Women who received low-molecular weight heparin reported significantly more treatment-related adverse events than women in the standard surveillance group (43.9% vs. 26.5%; OR = 2.17; 95% CI, 1.32-3.55). These included bruising, skin reactions at the injection site and minor bleeding.
Clinical implications
Although she expressed disappointment that the intervention in this study did not increase the live birth rate for women in this subgroup, Middledorp said she was pleased that the results have perhaps settled a decades-long debate.
“We should not say that this is a negative study,” she said. “In practice, we can reassure women with a history of recurrent pregnancy loss that they have a 70% chance of having a healthy baby in their next pregnancy.”
Because low-molecular-weight heparin did not increase the live birth rate, Middledorp said it should not be used to treat women for the prevention of miscarriage, nor is it necessary to test for inherited thrombophilia among women who have recurrent miscarriages.
Reference s :
- Kaandorp SP, et al. N Engl J Med. 2010;doi:10.1056/NEJMoa1000641.
- Quenby S, et al. Abstract LBA-5. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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Quenby S, et al. Abstract LBA-5. Presented at: ASH Annual Meeting and Exposition; Dec. 10-13, 2022; New Orleans.
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