Pravastatin versus Placebo in Pregnancies at High Risk of Term Preeclampsia.

Abstract

BACKGROUND: Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with detection rate of about 75%, at screen positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1,120 women with singleton pregnancies at high-risk of term preeclampsia to receive pravastatin, at a dose of 20 mg per day, or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention-to-treat. RESULTS: A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80/548) participants in the pravastatin group and in 13.6% (74/543) in the placebo group. Allowing for the effect of risk at the time of screening and participating centre, the mixed effects Cox regression showed no evidence of an effect of pravastatin; hazard ratio (statin/placebo) 1.08 (95% confidence interval: 0.78, 1.49; p=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, previous pregnancy history, adherence and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization Adherence was good, with reported intake of 80% or more of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events.