Aspirin discontinuation at 24 to 28 weeks gestation does not affect preeclampsia in high-risk patients

1. Patients who stopped taking aspirin in their third trimester were at no higher risk for developing preeclampsia compared to patients who continued taking the medication up until delivery.

2. The incidence of preeclampsia was approximately 1.5% and 1.7% among the intervention and control groups, respectively. 

Level of Evidence Rating: 1 (Excellent)

Study Rundown: Preeclampsia is an obstetrical condition characterized by hypertension and proteinuria, which develop after 20 weeks gestation. Complications associated with preeclampsia include other placental pathologies and HELLP syndrome, which significantly increase the risk of maternal and fetal morbidity and mortality. Aspirin is known to reduce the risk of preterm preeclampsia, most effectively initiated within the first trimester of pregnancy. Unfortunately, the use of aspirin may also increase the likelihood of bleeding complications at the time of delivery, therefore it is of interest whether aspirin can safely be stopped later in pregnancy. The soluble fms-like tyrosine kynase–1 to placental growth factor ratio (sFlt-1:PlGF) is a known marker of preeclampsia which arises secondary to placental ischemia. This trial sought to evaluate whether cessation of aspirin therapy in pregnant women identified to be at high risk of preeclampsia, but with a normal sFlt-1:PlGF, affected the risk of preterm preeclampsia.

936 patients were randomized and completed this study. The incidence of preeclampsia at any gestational age was found to be higher in the control group than in the intervention group, as was the number of placental abruptions. 1.48% of participants in the intervention group were diagnosed with preterm preeclampsia, as were 1.73% of patients in the control group. The median gestational age of delivery amongst patients was 35.1 weeks in both groups and there were no significant differences 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.

This randomized controlled trial by Mendoza et al demonstrated that cessation of aspirin therapy between 24 and 28 weeks in patients at high risk for preeclampsia and normal sFlt-1:PlGF was non-inferior to the continuation of aspirin until delivery. There were no significant differences in the rate of preterm preeclampsia or bleeding-related complications. Strengths of this trial include the randomized study design and robust statistical analysis. Conversely, one limitation of this work was that it was underpowered to detect the effect of aspirin discontinuation on rarer events. Additionally, the 1.9% absolute difference that was established as a noninferiority threshold a priori was somewhat controversial, as some literature suggests that 1.6% would be more appropriate.

Click here to read this study in JAMA

Relevant reading: Prevention of preeclampsia with aspirin

In-Depth [randomized controlled trial]: A multicenter randomized controlled trial was conducted in Spain. Eligible patients were: pregnant, above the age of 18, carrying a singleton fetus with a gestational age between 24 and 28 weeks, had a high risk (>1/170) of developing preeclampsia on First Trimester Screening and had started taking aspirin (150mg daily) prior to 16 weeks, 6 days of gestation. Finally, eligible patients had to have an sFlt-1:PlGF less than or equal to 38 (low) during the study period. Participants were randomized in a 1:1 fashion to the control group (continue aspirin) or the intervention group (aspirin cessation). Study visits were conducted every 4 weeks from randomization up to 36 weeks gestation and weekly thereafter until delivery. The primary outcome was the diagnosis of preterm preeclampsia. A noninferiority threshold of 1.9% was determined a priori.

The incidence of preeclampsia at any gestational age was higher in the control group than in the intervention group (13.3% vs. 8.2%, p<0.05). As well, there were more placental abruptions (3 vs. 0, p=0.12) in the control group, which was clinically significant due to the severity of this complication, if not statistically significant. 1.48% of patients in the intervention group and 1.73% of patients in the control group developed preterm preeclampsia, which was not a statistically significant difference (absolute difference -0.25%, 95% confidence interval -1.86-1.36%). These results were robust to sensitivity analysis in which missing data were imputed. The rate of bleeding complications was also not different between the two groups, with 8.0% in the intervention group and 12.7% in the control group (absolute difference 4.71%, 95% confidence interval -8.61%-0.81%).

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