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

Research output: Contribution to journalArticlepeer-review

Authors

  • StAmP trial Collaborative Group

External organisations

  • Aston Medical Research Institute, Aston Medical School, Aston Triangle, Birmingham, West Midlands B4 7ET, UK
  • University College London Hospitals NHS Foundation Trust
  • Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK.
  • Barts and the London Medical School
  • University of Nottingham

Abstract

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.

Details

Original languageEnglish
Pages (from-to)478-488
Number of pages11
JournalBJOG: An International Journal of Obstetrics & Gynaecology
Volume127
Issue number4
Early online date12 Nov 2019
Publication statusPublished - Mar 2020

Keywords

  • anti‐angiogenic factor, double‐blind, perinatal mortality, placebo‐controlled, pravastatin, pre‐eclampsia, randomized trial, statin, pre-eclampsia, randomised trial, placebo-controlled, Anti-angiogenic factor, double-blind, Double-Blind Method, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, Humans, Vascular Endothelial Growth Factor Receptor-1/blood, Pre-Eclampsia/blood, Gestational Age, Pregnancy, Adult, Female, Pravastatin/administration & dosage

ASJC Scopus subject areas