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

Research output: Contribution to journalArticle

Authors

  • StAmP trial Collaborative Group

External organisations

  • Aston Medical Research Institute, Aston Medical School, Aston Triangle, Birmingham, West Midlands B4 7ET, UK
  • UCL EGA Institute for Women's Health, University College London, London, UK.
  • Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK.
  • Barts and the London Medical School
  • Nottingham Clinical Trials Unit, University of Nottingham, Notthingham, UK.

Abstract

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.

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