Pravastatin for early‐onset preeclampsia: a randomized, blinded, placebo‐controlled trial

Objective Women with preeclampsia have elevated circulating levels of soluble fms‐like tyrosine kinase‐1 (sFlt‐1). Statins can reduce sFlt‐1 from cultured cells and improve pregnancy outcome in animals with a preeclampsia‐like syndrome. We investigated the effect of pravastatin on plasma sFlt‐1 levels during preeclampsia. Design Blinded (clinician and participant), proof of principle, placebo‐controlled trial Setting 15 UK maternity units. Population We used a minimization algorithm to assign 62 women with early‐onset preeclampsia (24+0 ‐ 31+6 weeks' gestation) to receive pravastatin 40mg daily (n=30) or matched placebo (n=32), from randomization to childbirth. Primary outcome Difference in mean plasma sFlt‐1 levels over the first three days following randomization. Results The difference in the mean maternal plasma sFlt‐1 levels over the first three days after randomisation between the pravastatin (n=27) and placebo (n=29) groups was 292pg/mL (95%CI: ‐1175‐ 592; p=0.5), and over days 1‐14 was 48pg/ml (95% CI ‐1009 to 913; p=0.9). Women who received pravastatin had a similar length of pregnancy following randomization compared with those who received placebo (Hazard ratio 0.84; 95%CI: 0.50‐1.40; p=0.6). The median time from randomization to childbirth was 9 days (IQR 5‐14 days) for the pravastatin group and 7 days (IQR 4‐11 days) for the placebo group. There were 3 perinatal deaths in the placebo‐treated group and no deaths or serious adverse events attributable to pravastatin. Conclusions We found no evidence that pravastatin lowered maternal plasma sFlt‐1 levels once early onset preeclampsia had developed. Pravastatin appears to have no adverse perinatal effects.