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

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; 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

doi:10.1111/1471-0528.16013

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

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

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

Aston Medical Research Institute Aston Medical School Aston University Birmingham UK
King Fahad Centre for Medical Research King Abdulaziz University Jeddah Saudi Arabia
UCL Hospitals NHS Foundation Trust
University of Birmingham
Barking, Havering & Redbridge University Hospitals NHS Trust Romford UK
Univ Coll London Hosp, Queen Mary University London, University of London, University College London, Dept Microbiol
University of Nottingham

Research output: Contribution to journal › Article › peer-review

124 Citations (Scopus)

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.

Original language	English
Pages (from-to)	478-488
Number of pages	11
Journal	BJOG
Volume	127
Issue number	4
Early online date	12 Nov 2019
DOIs	https://doi.org/10.1111/1471-0528.16013
Publication status	Published - 1 Mar 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Anti-angiogenic factor
double-blind
perinatal mortality
placebo-controlled
pravastatin
pre-eclampsia
randomised trial
statin

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10.1111/1471-0528.16013

Cite this

Ahmed, A., Williams, D., Cheed, V., Middleton, L., Ahmad, S., Wang, K., Vince, A., Hewett, P., Spencer, K., Khan, K., Daniels, J., Barber, K., Kilby, M., Knox, E., Sellman, T., Trinham, P., Tuffnell, D., Jones, V., Syson, J., ... Brown, S. (2020). Pravastatin for early‐onset pre‐eclampsia: a randomised, blinded, placebo‐controlled trial. BJOG, 127(4), 478-488. https://doi.org/10.1111/1471-0528.16013

@article{855d5b44a53c4b4787a1b0dce894f38e,

title = "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. ",

keywords = "Anti-angiogenic factor, double-blind, perinatal mortality, placebo-controlled, pravastatin, pre-eclampsia, randomised trial, statin",

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

year = "2020",

month = mar,

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doi = "10.1111/1471-0528.16013",

language = "English",

volume = "127",

pages = "478--488",

journal = "BJOG",

issn = "1470-0328",

publisher = "John Wiley and Sons Inc.",

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Ahmed, A, Williams, D, Cheed, V, Middleton, L, Ahmad, S, Wang, K, Vince, A, Hewett, P, Spencer, K, Khan, K, Daniels, J, Barber, K, Kilby, M, Knox, E, Sellman, T, Trinham, P, Tuffnell, D, Jones, V, Syson, J, Shah, N, Deeks, L, Carter, W, Dorman, E, Thomas, S, Harrington, D, Higgins, N, Wilmott‐powell, M, Simpson, N, Dolby, V, Bricker, L, Walkinshaw, S, Houghton, G, Longworth, H, Williamson, C, Dhanjal, M, Noori, M, Machirori, M, Howard, R, Murray, R, Weist, S, Denison, F, Crawford, I, Robson, S, Allan, C, Myers, J, Bernatavicius, G, Moorhead, L, Chappell, L, Nelson‐piercy, C, Williams, D , Daley, R, Rosas, M, Greer, I, Vitek, L, Shennan, A, Marlow, N, Barnard, AM, Thornton, J, Rennie, J, Peacock, J, Gao Smith, F, Hyde, C, Crawford, I, Cudmore, M, Furmston, A, Fulcher, L, Homer, L, Howman, A, Hilken, N & Brown, S 2020, 'Pravastatin for early‐onset pre‐eclampsia: a randomised, blinded, placebo‐controlled trial', BJOG, vol. 127, no. 4, pp. 478-488. https://doi.org/10.1111/1471-0528.16013

TY - JOUR

T1 - Pravastatin for early‐onset pre‐eclampsia: a randomised, blinded, placebo‐controlled trial

AU - Ahmed, A

AU - Williams, Dj

AU - Cheed, V

AU - Middleton, Lj

AU - Ahmad, S

AU - Wang, K

AU - Vince, At

AU - Hewett, P

AU - Spencer, K

AU - Khan, Ks

AU - Daniels, Jp

AU - Barber, Katherine

AU - Kilby, Mark

AU - Knox, Ellen

AU - Sellman, Tara

AU - Trinham, Paula

AU - Tuffnell, Derek

AU - Jones, Vicky

AU - Syson, Jennifer

AU - Shah, Neil

AU - Deeks, Laurie

AU - Carter, Wendy

AU - Dorman, Ed

AU - Thomas, Susannah

AU - Harrington, Deborah

AU - Higgins, Nicola

AU - Wilmott‐powell, Mirriam

AU - Simpson, Nigel

AU - Dolby, Vivian

AU - Bricker, Leanne

AU - Walkinshaw, Steve

AU - Houghton, Gillian

AU - Longworth, Heather

AU - Williamson, Catherine

AU - Dhanjal, Mandish

AU - Noori, Muna

AU - Machirori, Mavis

AU - Howard, Richard

AU - Murray, Rebecca

AU - Weist, Sarah

AU - Denison, Fiona

AU - Crawford, Isobel

AU - Robson, Stephen

AU - Allan, Carly

AU - Myers, Jenny

AU - Bernatavicius, Giovanna

AU - Moorhead, Lynsey

AU - Chappell, Lucy

AU - Nelson‐piercy, Catherine

AU - Williams, David

AU - Daley, Rebecca

AU - Rosas, Miguel

AU - Greer, Ian

AU - Vitek, Libor

AU - Shennan, Andy

AU - Marlow, Neil

AU - Barnard, Ann Marie

AU - Thornton, Jim

AU - Rennie, Janet

AU - Peacock, Janet

AU - Gao Smith, Fang

AU - Hyde, Carolyn

AU - Crawford, Isobel

AU - Cudmore, Melissa

AU - Furmston, Alex

AU - Fulcher, Leanne

AU - Homer, Leanne

AU - Howman, Andrew

AU - Hilken, Nicholas

AU - Brown, Stephen

PY - 2020/3/1

Y1 - 2020/3/1

N2 - 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.

AB - 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.

KW - Anti-angiogenic factor

KW - double-blind

KW - perinatal mortality

KW - placebo-controlled

KW - pravastatin

KW - pre-eclampsia

KW - randomised trial

KW - statin

UR - https://www.scopus.com/pages/publications/85077081210

U2 - 10.1111/1471-0528.16013

DO - 10.1111/1471-0528.16013

M3 - Article

SN - 1470-0328

VL - 127

SP - 478

EP - 488

JO - BJOG

JF - BJOG

IS - 4

ER -

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

Abstract

UN SDGs

Keywords

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