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

Ahmed, Asif; Williams, David J.; Cheed, Versha; Middleton, Lee J.; Ahmad, Shakil; Wang, Keqing; Vince, Alex T.; Hewett, Peter; Spencer, Kevin; Khan, Khalid S.; Daniels, Jane P.; StAmP trial collaborative group

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.

Citation

Ahmed, A., Williams, D. J., Cheed, V., Middleton, L. J., Ahmad, S., Wang, K., Vince, A. T., Hewett, P., Spencer, K., Khan, K. S., Daniels, J. P., & StAmP trial collaborative group. (2020). Pravastatin for early‐onset preeclampsia: a randomized, blinded, placebo‐controlled trial. BJOG: An International Journal of Obstetrics and Gynaecology, 127(4), 478-488. https://doi.org/10.1111/1471-0528.16013

• Journal Article Type: Article
• Acceptance Date: Nov 4, 2019
• Online Publication Date: Nov 12, 2019
• Publication Date: Mar 1, 2020
• Deposit Date: Nov 19, 2019
• Publicly Available Date: Nov 13, 2020
• Journal: BJOG: An International Journal of Obstetrics & Gynaecology
• Print ISSN: 1470-0328
• Electronic ISSN: 1471-0528
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 127
• Issue: 4
• Pages: 478-488
• DOI: https://doi.org/10.1111/1471-0528.16013
• Keywords: Anti-angiogenic factor, Double-blind, Perinatal mortality, Placebo-controlled, Pravastatin, Pre-eclampsia, Randomized trial, Statin
• Public URL: https://nottingham-repository.worktribe.com/output/3334361
• Publisher URL: https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1111/1471-0528.16013
• Additional Information: This is the peer reviewed version of the following article: Ahmed, A, Williams, DJ, Cheed, V, Middleton, LJ, Ahmad, S, Wang, K, Vince, AT, Hewett, P, Spencer, K, Khan, KS, Daniels, JP, for the StAmP trial Collaborative Group. Pravastatin for early‐onset pre‐eclampsia: a randomised, blinded, placebo‐controlled trial. BJOG 2020; 127: 478– 488. , which has been published in final form at https://doi.org/10.1111/1471-0528.16013. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
• Contract Date: Nov 19, 2019