Aspirin Discontinuation at 24-28 Weeks Has No Impact on Preeclampsia in High-risk Patients

Pregnant persons at high risk of preeclampsia who discontinued aspirin therapy at 24 to 28 weeks of gestation were at no greater risk for the complication than those who continued treatment up to 37 weeks according to findings published online February 21, 2023, in JAMA.

The study found that preterm preeclampsia incidence was 1.48% in the group that continued taking aspirin through delivery and 1.73% among those who stopped the drug in the in the third trimester.

Study authors cite research demonstrating that aspirin is effective in reducing the incidence of preterm preeclampsia by 62% and most effective when initiated within the first trimester. Risks associated with aspirin therapy, however, include bleeding complications at the time of delivery.

Despite such safety concerns, the authors add, the recommendations available on when to discontinue treatment are inconsistent. In fact, stopping aspirin before term has been investigated in just one study. The research team’s primary question for this study, thus, was whether aspirin could be stopped safely later in pregnancy among women at high risk for preeclampsia and, importantly, who also had a normal soluble fms-like tyrosine kynase–1 to placental growth factor ratio (sFlt-1:PlGF). An increase in the ratio is a known marker of preeclampsia and is a result of placental ischemia.

The study was conducted at 9 maternity hospitals across Spain and enrolled patients who werepregnant, aged >18 years, carrying a singleton fetus with a gestational age between 24 and 28 weeks. Participants were required to be at high risk (>1/170) of developing preeclampsia, and to have initiated aspirin therapy (150mg daily) before 16 weeks, 6 days of gestation.

Finally, to be eligible for the final analysis, patients had to have an sFlt-1:PlGF ≤38 (low) during the study period.

Between 24 and 28 weeks of gestation, participants were randomly assigned, in a 1:1 ratio, to either continue aspirin treatment (control group) or discontinue aspirin treatment (intervention group). From the time of randomization up to gestation week 36, patients attended study visits every 4 weeks and then every week subsequently until delivery.

The primary outcome was delivery due to preeclampsia before 37 weeks gestation. Investigators determined a priori a noninferiority threshold of 1.9%.

FINDINGS

The final cohort with available data for primary and secondary outcomes numbered 936 (473 randomized to discontinue aspirin, 463 to continue aspirin). Participant’s mean age was 32.4 years; 3.4% were Black and 93% were White.

There were 7 cases of preterm preeclampsia among the 473 pregnant participants (1.48%) in the intervention group and among 8 of 463 pregnant participants (1.73%) in the control group (absolute difference, −0.25% [95% CI, −1.86% to 1.36%]). The median gestational age of delivery for cases of preterm preeclampsia in both the intervention and control groups was 35.1 weeks (P=.42).

The researchers report observing no significant differences between the groups in the rates of most adverse events at delivery. At least 1 bleeding complication occurred in 8% of patients in the intervention group and 12.7% of patients in the control group, suggesting that discontinuation of aspirin could potentially reduce the risk of minor bleeding complications at ≥37 weeks of gestation.

Investigators emphasize the main strength of the work, the first of its kind, is the novelty of the evidence that suggests continuation of aspirin therapy in pregnant persons at high risk of preterm preeclampsia until 36 weeks of gestation may not be necessary in all cases.

Among the benefits of earlier discontinuation, they add, could be reduced risk of bleeding complications and pregnancy complications at term as well as reduced “maternal anxiety, treatment costs, number of visits, ultrasound scans, and iatrogenic interventions in a cohort of healthy pregnant individuals in which more than 95% of cases are actually false-positives.”

One limitation the team notes is that the study was underpowered to detect the effect of stopping aspirin on events less common than preeclampsia. Also limiting generalizability of the findings was the homogeneous racial and ethnic makeup of the cohort and the open-label design, allowing participant and clinician awareness of group assignment.

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. J Am Medical Assoc. Published online February 21, 2023. doi:10.1001/jama.2023.0691