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

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A Ahmed, Dj Williams, V Cheed, Lj Middleton, S Ahmad, K Wang, At Vince, P Hewett, K Spencer, Ks Khan, Jp Daniels, Katherine Barber, Mark Kilby, Ellen Knox, Tara Sellman, Paula Trinham, Derek Tuffnell, Vicky Jones, Jennifer Syson, Neil Shah & 50 more Laurie Deeks, Wendy Carter, Ed Dorman, Susannah Thomas, Deborah Harrington, Nicola Higgins, Mirriam Wilmott‐powell, Nigel Simpson, Vivian Dolby, Leanne Bricker, Steve Walkinshaw, Gillian Houghton, Heather Longworth, Catherine Williamson, Mandish Dhanjal, Muna Noori, Mavis Machirori, Richard Howard, Rebecca Murray, Sarah Weist, Fiona Denison, Isobel Crawford, Stephen Robson, Carly Allan, Jenny Myers, Giovanna Bernatavicius, Lynsey Moorhead, Lucy Chappell, Catherine Nelson‐piercy, David Williams, Rebecca Daley, Miguel Rosas, Ian Greer, Libor Vitek, Andy Shennan, Neil Marlow, Ann Marie Barnard, Jim Thornton, Janet Rennie, Janet Peacock, Fang Gao Smith, Carolyn Hyde, Isobel Crawford, Melissa Cudmore, Alex Furmston, Leanne Fulcher, Leanne Homer, Andrew Howman, Nicholas Hilken, Stephen Brown

Original languageEnglish
Pages (from-to)478-488
Number of pages11
JournalBJOG
Volume127
Issue number4
Early online date12 Nov 2019
DOIs
Accepted/In press4 Nov 2019
E-pub ahead of print12 Nov 2019
Published1 Mar 2020

King's Authors

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.

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