Pravastatin fails to reduce preeclampsia in high-risk pregnancies
Pravastatin compared with placebo did not reduce incidence of delivery with preeclampsia among pregnant women at high risk, according to findings published in Circulation.
“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%,” Moritz Döbert, MD, from the Fetal Medicine Research Institute at King’s College Hospital, London, and colleagues wrote. “One potentially beneficial pharmacological intervention for the high-risk group is the use of pravastatin, a hydrophilic, 3-hydrocy-3-methyl-glutaryl-coenzyme A reductase inhibitor.”
For the multicenter, double-blind, placebo-controlled trial, researchers enrolled 1,091 pregnant women at high risk for term preeclampsia. Participants were randomly assigned to pravastatin (20 mg/day; n = 548; mean age, 32.9 years) or placebo (n = 543; mean age, 32.5 years) from 35 to 37 gestational weeks until delivery or week 41.
The primary outcome was preeclampsia at delivery any time after randomization. Secondary outcomes included gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death or neonatal morbidity.
Researchers observed preeclampsia among 14.6% of participants in the pravastatin group and 13.6% of participants in the placebo group. There was no evidence of an effect of pravastatin (HR = 1.08; 95% CI, 0.78-1.49; P = .65). There was also no evidence of an association between the effect of pravastatin and estimated preeclampsia risk, previous pregnancy history, adherence and aspirin treatment.
In addition, researchers observed no significant between-group difference in incidence of any of the secondary outcomes. There was also no significant between-group difference in treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations at 1 and 3 weeks.
Participants demonstrated good overall adherence to their randomization groups, with a reported 80% or more intake of the required number of tablets in 89.1% of participants.
There were two cases of at least one serious adverse event among participants in the pravastatin group and six cases among participants in the placebo group, with no significant between-group difference.
“It is possible that considerably higher doses and longer duration of treatment with pravastatin are needed to restore the balance in the circulating levels of angiogenic and anti-angiogenic factor and thereby prevent the development of preeclampsia,” the researchers wrote.