Pravastatin for early‐onset pre‐eclampsia: a randomised, blinded, placebo‐controlled trial

Abstract

Summary Objective Women with pre‐eclampsia 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 pre‐eclampsia‐like syndrome. We investigated the effect of pravastatin on plasma sFlt‐1 levels during pre‐eclampsia. Design Blinded (clinician and participant), proof of principle, placebo‐controlled trial. Setting Fifteen UK maternity units. Population We used a minimisation algorithm to assign 62 women with early‐onset pre‐eclampsia (24+0–31+6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth. Primary outcome Difference in mean plasma sFlt‐1 levels over the first 3 days following randomisation. Results The difference in the mean maternal plasma sFlt‐1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days (interquartile range [IQR] 5–14 days) for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three 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 pre‐eclampsia had developed. Pravastatin appears to have no adverse perinatal effects. Tweetable abstract Pravastatin does not improve maternal plasma sFlt‐1 or placental growth factor levels following a diagnosis of early preterm pre‐eclampsia #clinicaltrial finds.

Pravastatin for preeclampsia: From animal to human

“…The limitations of pravastatin for preeclampsia should also be noted. Ahmed and colleagues reported the effect of pravastatin on plasma sFLT1 levels during early onset preeclampsia (StaMP trial) 33 (Table 1). Sixty-two women with preeclampsia (24 +0 -31 +6 weeks of gestation) were divided into two groups by a minimization algorithm.…”

“…However, it is worth noting that there were three perinatal deaths in the placebo-treated group and no deaths or serious adverse events attributable to pravastatin use. 33…”

Hydroxychloroquine as a Preventive and Therapeutic Option in Preeclampsia – a Literature Review

“…While statins were reported to reduce sFlt-1 in a preclinical setting, no final conclusion could be drawn in a clinical trial so far, due to the low case numbers. However, the impact appears to be lower than estimated [37,38].…”

Placental growth factor in suspected preterm pre‐eclampsia: a review of the evidence and practicalities of implementation

“…Treatment trials for pre‐eclampsia may be improved through targeted patient selection with a specific phenotype of placental disease and biomarkers may prove robust outcome measures for prevention trials. To this effect, sFlt‐1 was used as the primary outcome for the first randomised controlled trial of pravastatin for early‐onset pre‐eclampsia 43 …”