Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial.
Level 2 - randomized trial
Multi-center international randomized controlled trial
PubMed 37271152 · doi:10.1016/S0140-6736(23)00693-1
What was done
An international, open-label, randomized controlled trial (ALIFE2) across 40 hospitals in five countries evaluated whether low-molecular-weight heparin (LMWH) improves livebirth rates in women aged 18–42 with two or more pregnancy losses and confirmed inherited thrombophilia. Conceived participants were randomly assigned 1:1 to receive low-dose LMWH (started at or before 7 weeks' gestation until the end of pregnancy) alongside standard care, or standard care alone. The primary outcome was livebirth rate.
What was found
Of 326 randomized women, 116 of 162 (72%) with primary outcome data in the LMWH group and 112 of 158 (71%) in the standard care group had livebirths (adjusted odds ratio 1.08, 95% CI 0.65 to 1.78; absolute risk difference 0.7%, 95% CI -9.2% to 10.6%). Adverse events were reported in 39 of 164 women (24%) receiving LMWH and 37 of 162 women (23%) receiving standard care.
Why it matters
This trial demonstrates that LMWH does not increase livebirth rates in women with recurrent pregnancy loss and inherited thrombophilia, challenging common clinical practice and arguing against routine thrombophilia screening in this setting.
Limits
The trial used an open-label design rather than a placebo control. Recruitment was slow and required screening 10,625 women over nearly nine years to randomize 326. Disaggregated outcomes by specific inherited thrombophilia subtypes are not reported in the abstract.
Cited by
- contradicts Universal prophylactic use of enoxaparin in women following a first or second miscarriage would result in 2,000 to 15,000 additional live births per year in the United States.