Ahmed, Asif, Williams, David, Cheed, Versha, Middleton, Lee J, Ahmad, Shakil, Wang, Keqing, 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 and Brown, Stephen (2020). Pravastatin for early-onset pre-eclampsia:a randomised, blinded, placebo-controlled trial. BJOG, 127 (4), pp. 478-488.
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 |
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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 |
Publication ISSN: | 1471-0528 |
Last Modified: | 10 Oct 2024 16:22 |
Date Deposited: | 20 Nov 2019 13:16 |
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
(
0000-0002-8755-8546)
Williams, David Cheed, Versha Middleton, Lee J Ahmad, Shakil ( 0000-0002-9294-0475) Wang, Keqing ( 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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