Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial

M Mendoza, E Bonacina, P Garcia-Manau, M López, S Caamiña, À Vives, E Lopez-Quesada, M Ricart, A Maroto, Mingo L de, E Pintado, R Ferrer-Costa, Lourdes Martin, Alicia Rodríguez-Zurita, Esperanza García, Mar Pallarols, Laia Vidal-Sagnier, Miereia Teixidor, Carmen Orizales-Lago, Adela Pérez-GómezVanesa Ocaña, Linda Puerto, Pilar Millán, Mercè Alsius, Sonia Díaz, Nerea Maíz, Elena Carreras, A Suy

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Abstract

IMPORTANCE Aspirin reduces the incidence of preterm preeclampsia by 62% in pregnant individuals at high risk of preeclampsia. However, aspirin might be associated with an increased risk of peripartum bleeding, which could be mitigated by discontinuing aspirin before term (37 weeks of gestation) and by an accurate selection of individuals at higher risk of preeclampsia in the first trimester of pregnancy.OBJECTIVE To determine whether aspirin discontinuation in pregnant individuals with normal soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1:PlGF) ratio between 24 and 28 weeks of gestation was noninferior to aspirin continuation to prevent preterm preeclampsia.DESIGN, SETTING, AND PARTICIPANTS Multicenter, open-label, randomized, phase 3, noninferiority trial conducted in 9 maternity hospitals across Spain. Pregnant individuals (n = 968) at high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24 to 28 weeks of gestation were recruited between August 20, 2019, and September 15, 2021; of those, 936 were analyzed (intervention: n = 473; control: n = 463). Follow-up was until delivery for all participants.INTERVENTIONS Enrolled patients were randomly assigned in a 1:1 ratio to aspirin discontinuation (intervention group) or aspirin continuation until 36 weeks of gestation (control group).MAIN OUTCOMES AND MEASURES Noninferiority was met if the higher 95% CI for the difference in preterm preeclampsia incidences between groups was less than 1.9%.RESULTS Among the 936 participants, the mean (SD) age was 32.4 (5.8) years; 3.4% were Black and 93% were White. The incidence of preterm preeclampsia was 1.48%(7/473) in the intervention group and 1.73%(8/463) in the control group (absolute difference, -0.25% [95% CI, -1.86% to 1.36%]), indicating noninferiority.CONCLUSIONS AND RELEVANCE Aspirin discontinuation at 24 to 28 weeks of gestation was noninferior to aspirin continuation for preventing preterm preeclampsia in pregnant individuals at high risk of preeclampsia and a normal sFlt-1:PlGF ratio.
Original languageEnglish
Pages (from-to)542-550
Number of pages9
JournalJAMA
Volume329
Issue number7
DOIs
Publication statusPublished - 21 Feb 2023

Keywords

  • Adult
  • Aspirin/adverse effects
  • Biomarkers/blood
  • Female
  • Hemorrhage/blood
  • Humans
  • Infant, Newborn
  • Peripartum Period
  • Placenta Growth Factor/blood
  • Pre-Eclampsia/blood
  • Pregnancy
  • Pregnancy Complications/blood
  • Pregnancy Trimester, First
  • Premature Birth/blood
  • Vascular Endothelial Growth Factor Receptor-1/blood
  • Withholding Treatment

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