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

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.

Publication DOI: https://doi.org/10.1111/1471-0528.16013
Divisions: College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2019 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding: Medical Research Council. Grant Number: G0701824
Uncontrolled Keywords: Anti-angiogenic factor,double-blind,perinatal mortality,placebo-controlled,pravastatin,pre-eclampsia,randomised trial,statin,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,Obstetrics and Gynaecology
Full Text Link:
Related URLs: https://onlinel ... 1471-0528.16013 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-03-01
Published Online Date: 2019-11-12
Accepted Date: 2019-11-04
Authors: Ahmed, Asif (ORCID Profile 0000-0002-8755-8546)
Williams, David
Cheed, Versha
Middleton, Lee J
Ahmad, Shakil (ORCID Profile 0000-0002-9294-0475)
Wang, Keqing (ORCID Profile 0000-0001-6239-6344)
Vince, Alex T
Hewett, Peter
Spencer, Kevin
Khan, Khalid S
Daniels, Jane P
Barber, Katherine
Kilby, Mark
Knox, Ellen
Sellman, Tara
Trinham, Paula
Tuffnell, Derek
Jones, Vicky
Syson, Jennifer
Shah, Neil
Deeks, Laurie
Carter, Wendy
Dorman, Ed
Thomas, Susannah
Harrington, Deborah
Higgins, Nicola
Wilmott‐powell, Mirriam
Simpson, Nigel
Dolby, Vivian
Bricker, Leanne
Walkinshaw, Steve
Houghton, Gillian
Longworth, Heather
Williamson, Catherine
Dhanjal, Mandish
Noori, Muna
Machirori, Mavis
Howard, Richard
Murray, Rebecca
Weist, Sarah
Denison, Fiona
Crawford, Isobel
Robson, Stephen
Allan, Carly
Myers, Jenny
Bernatavicius, Giovanna
Moorhead, Lynsey
Chappell, Lucy
Nelson‐piercy, Catherine
Williams, David
Daley, Rebecca
Rosas, Miguel
Greer, Ian
Vitek, Libor
Shennan, Andy
Marlow, Neil
Marie Barnard, Ann
Thornton, Jim
Rennie, Janet
Peacock, Janet
Gao Smith, Fang
Hyde, Carolyn
Crawford, Isobel
Cudmore, Melissa
Furmston, Alex
Fulcher, Leanne
Homer, Leanne
Howman, Andrew
Hilken, Nicholas
Brown, Stephen

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