Discontinuing aspirin at 24 to 28 weeks gestation feasible for preeclampsia prevention while reducing bleeding risk: JAMA

Previous studies have shown that aspirin causes a reduction in the incidence of preeclampsia by 62% in pregnant individuals at high preeclampsia risk. However, aspirin might be tied to an increased risk of peripartum bleeding, which could be mitigated by aspirin discontinuation before term, i.e. 37 weeks of pregnancy and by accurately selecting individuals at high preeclampsia risk in the pregnancy's first trimester.

Against the above background, Manel Mendoza and colleagues from Spain aimed to determine whether aspirin discontinuation in pregnant women with normal soluble fms-like tyrosine kinase–1 to placental growth factor (sFlt-1:PlGF) ratio between gestation weeks 24 and 28 weeks of gestation was noninferior to aspirin continuation for the prevention of preterm preeclampsia.

They addressed the question, "can aspirin be discontinued at 24 to 28 weeks of gestation among pregnant women taking aspirin to prevent preterm preeclampsia when the sFlt-1:PlGF ratio is normal?"

For this purpose, the researchers conducted a randomized, open-label, multicenter, phase 3, noninferiority trial in 9 maternity hospitals across Spain. They included 968 pregnant women at high preeclampsia risk during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at gestation weeks 24 to 28 between 2019 and 2021. Of 968, 936 were analyzed; 473 were in the intervention, and 463 were in control. All participants were followed-up until delivery.

Enrolled patients were randomly allocated in a 1:1 ratio to the intervention group (aspirin discontinuation) or control group (aspirin continuation) until 36 weeks of gestation.

Noninferiority was met if the higher difference in preterm preeclampsia incidences between groups was less than 1.9%.

The study led to the following findings:

• Among the 936 participants, the mean age was 32.4 years; 3.4% were Black, and 93% were White.
• The incidence of preterm preeclampsia was 1.48% in the intervention group and 1.73% in the control group (absolute difference, −0.25%), indicating noninferiority.

To conclude, aspirin discontinuation at gestation weeks 24 to 28 was noninferior to aspirin continuation for preterm preeclampsia prevention in pregnant women at high preeclampsia risk and a normal sFlt-1:PlGF ratio.

Reference:

Mendoza M, Bonacina E, Garcia-Manau P, et al. Aspirin Discontinuation at 24 to 28 Weeks’ Gestation in Pregnancies at High Risk of Preterm Preeclampsia: A Randomized Clinical Trial. JAMA. 2023;329(7):542–550. doi:10.1001/jama.2023.0691