Christopher J. Robinson, MD, MSCR
Does aspirin alone or combined with nadroparin increase live births in women with unexplained recurrent miscarriage?
Randomized placebo-controlled trial (Anticoagulants for Living Fetuses [ALIFE]). Current Controlled Trials ISRCTN58496168.
Blinded (patients and clinicians for aspirin and placebo; data monitoring committee for all treatments).*
2 years or until pregnancy or decision not to become pregnant (trial was stopped early for apparent futility; 6% of women were still in follow-up).
3 university hospitals and 5 teaching hospitals in the Netherlands.
364 women 18 to 42 years of age (mean age 34 y) who had ≥ 2 previous unexplained miscarriages and were pregnant (≤ 6 wk gestation) or trying to become pregnant. Miscarriage was defined as loss of confirmed pregnancy, excluding biochemical pregnancy, at ≤ 20 weeks gestation and clinical manifestations of miscarriage (e.g., vaginal bleeding, abdominal pain, and cramps). Exclusion criteria were previous venous or arterial thromboembolism, endocrine disorders (e.g., diabetes mellitus), or need for anticoagulant treatment.
Acetylsalicylic acid (ASA) equivalent, 80 mg/d, plus subcutaneous nadroparin, 2850 IU/d (n = 123); ASA alone (n = 120); or placebo (n = 121). ASA and placebo were started at randomization and stopped at 36 gestational weeks of pregnancy, miscarriage, premature delivery, or diagnosis of ectopic pregnancy. Nadroparin was started at 6 gestational weeks of ultrasound-confirmed, intrauterine pregnancy and stopped when labor started.
Included live births, miscarriage, and adverse events. The trial had 80% power (α = 0.05) to detect a 15% absolute increase in live births with combination treatment from 75% with ASA alone or placebo.
93% (intention-to-treat analysis).
82% of women became pregnant. ASA alone or combined with nadroparin did not increase live births or reduce miscarriage more than placebo (Table). Combination treatment was associated with more injection site reactions and maternal bruising than placebo; ASA alone and placebo did not differ.
Aspirin alone or combined with nadroparin did not increase live births in women with unexplained recurrent miscarriage.
Acetylsalicylic acid (ASA) equivalent plus nadroparin (Comb) vs ASA alone vs placebo in women with unexplained recurrent miscarriage†
† RBR = relative benefit reduction; other abbreviations defined in Glossary. RBR, RRR, RRI, NNH, NNT, and CI calculated from data in article.
‡For combination therapy vs placebo. Aspirin and placebo did not differ.
Robinson CJ. Aspirin alone or combined with nadroparin did not increase live birth rates in women with unexplained recurrent miscarriage. Ann Intern Med. ;153:JC4–7. doi: 10.7326/0003-4819-153-8-201010190-02007
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Published: Ann Intern Med. 2010;153(8):JC4-7.
Cardiology, Coronary Risk Factors, Diabetes, Emergency Medicine, Endocrine and Metabolism.
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