Aspirin plus heparin or aspirin alone in women with recurrent miscarriage

Stef P. Kaandorp, Mariëtte Goddijn, Joris A.M. Van Der Post, Barbara A. Hutten, Harold R. Verhoeve, Karly Hamulyák, Ben Willem Mol, Nienke Folkeringa, Marleen Nahuis, Dimitri N.M. Papatsonis, Harry R. Büller, Fulco Van Der Veen, Saskia Middeldorp

Research output: Contribution to journalArticle

301 Citations (Scopus)

Abstract

Background: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. Methods: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. Results: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. Conclusions: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage.

LanguageEnglish
Pages1586-1596
Number of pages11
JournalNew England Journal of Medicine
Volume362
Issue number17
DOIs
Publication statusPublished - 29 Apr 2010

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kaandorp, S. P., Goddijn, M., Van Der Post, J. A. M., Hutten, B. A., Verhoeve, H. R., Hamulyák, K., ... Middeldorp, S. (2010). Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. New England Journal of Medicine, 362(17), 1586-1596. https://doi.org/10.1056/NEJMoa1000641
Kaandorp, Stef P. ; Goddijn, Mariëtte ; Van Der Post, Joris A.M. ; Hutten, Barbara A. ; Verhoeve, Harold R. ; Hamulyák, Karly ; Mol, Ben Willem ; Folkeringa, Nienke ; Nahuis, Marleen ; Papatsonis, Dimitri N.M. ; Büller, Harry R. ; Van Der Veen, Fulco ; Middeldorp, Saskia. / Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. In: New England Journal of Medicine. 2010 ; Vol. 362, No. 17. pp. 1586-1596.
@article{0ae32469ec7e495e87e48e23fd0719f3,
title = "Aspirin plus heparin or aspirin alone in women with recurrent miscarriage",
abstract = "Background: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. Methods: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. Results: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5{\%} in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8{\%} in the aspirin-only group, and 57.0{\%} in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95{\%} confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95{\%} CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1{\%} in the combination-therapy group, 61.6{\%} in the aspirin-only group, and 67.0{\%} in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95{\%} CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95{\%} CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. Conclusions: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage.",
author = "Kaandorp, {Stef P.} and Mari{\"e}tte Goddijn and {Van Der Post}, {Joris A.M.} and Hutten, {Barbara A.} and Verhoeve, {Harold R.} and Karly Hamuly{\'a}k and Mol, {Ben Willem} and Nienke Folkeringa and Marleen Nahuis and Papatsonis, {Dimitri N.M.} and B{\"u}ller, {Harry R.} and {Van Der Veen}, Fulco and Saskia Middeldorp",
year = "2010",
month = "4",
day = "29",
doi = "10.1056/NEJMoa1000641",
language = "English",
volume = "362",
pages = "1586--1596",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "17",

}

Kaandorp, SP, Goddijn, M, Van Der Post, JAM, Hutten, BA, Verhoeve, HR, Hamulyák, K, Mol, BW, Folkeringa, N, Nahuis, M, Papatsonis, DNM, Büller, HR, Van Der Veen, F & Middeldorp, S 2010, 'Aspirin plus heparin or aspirin alone in women with recurrent miscarriage', New England Journal of Medicine, vol. 362, no. 17, pp. 1586-1596. https://doi.org/10.1056/NEJMoa1000641

Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. / Kaandorp, Stef P.; Goddijn, Mariëtte; Van Der Post, Joris A.M.; Hutten, Barbara A.; Verhoeve, Harold R.; Hamulyák, Karly; Mol, Ben Willem; Folkeringa, Nienke; Nahuis, Marleen; Papatsonis, Dimitri N.M.; Büller, Harry R.; Van Der Veen, Fulco; Middeldorp, Saskia.

In: New England Journal of Medicine, Vol. 362, No. 17, 29.04.2010, p. 1586-1596.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aspirin plus heparin or aspirin alone in women with recurrent miscarriage

AU - Kaandorp, Stef P.

AU - Goddijn, Mariëtte

AU - Van Der Post, Joris A.M.

AU - Hutten, Barbara A.

AU - Verhoeve, Harold R.

AU - Hamulyák, Karly

AU - Mol, Ben Willem

AU - Folkeringa, Nienke

AU - Nahuis, Marleen

AU - Papatsonis, Dimitri N.M.

AU - Büller, Harry R.

AU - Van Der Veen, Fulco

AU - Middeldorp, Saskia

PY - 2010/4/29

Y1 - 2010/4/29

N2 - Background: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. Methods: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. Results: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. Conclusions: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage.

AB - Background: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. Methods: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. Results: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. Conclusions: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage.

UR - http://www.scopus.com/inward/record.url?scp=77951724860&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1000641

DO - 10.1056/NEJMoa1000641

M3 - Article

VL - 362

SP - 1586

EP - 1596

JO - New England Journal of Medicine

T2 - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 17

ER -

Kaandorp SP, Goddijn M, Van Der Post JAM, Hutten BA, Verhoeve HR, Hamulyák K et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. New England Journal of Medicine. 2010 Apr 29;362(17):1586-1596. https://doi.org/10.1056/NEJMoa1000641