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

• Published in: BJOG : an international journal of obstetrics and gynaecology Vol. 127; no. 4; pp. 478 - 488
• Main Authors: Ahmed, A, Williams, DJ, Cheed, V, Middleton, LJ, Ahmad, S, Wang, K, Vince, AT, Hewett, P, Spencer, K, Khan, KS, Daniels, JP, 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, Barnard, Ann Marie, Thornton, Jim, Rennie, Janet, Peacock, Janet, Gao Smith, Fang, Hyde, Carolyn, Cudmore, Melissa, Furmston, Alex, Fulcher, Leanne, Homer, Leanne, Howman, Andrew, Hilken, Nicholas, Brown, Stephen
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2020; John Wiley and Sons Inc
• Subjects: Adult; Anti‐angiogenic factor; Double-Blind Method; Double-blind studies; double‐blind; Eclampsia; Female; Gestation; Gestational Age; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Maternal Medicine; perinatal mortality; placebo‐controlled; Placenta; Plasma; Pravastatin; Pravastatin - administration & dosage; Pre-Eclampsia - blood; Pre-Eclampsia - drug therapy; Preeclampsia; Pregnancy; pre‐eclampsia; Protein-tyrosine kinase; randomised trial; statin; Statins; Vascular Endothelial Growth Factor Receptor-1 - blood; Vascular Endothelial Growth Factor Receptor-1 - drug effects; Womens health; randomised trial; statin; pravastatin; placebo-controlled; pre-eclampsia; Anti-angiogenic factor; perinatal mortality; double-blind
• ISSN: 1470-0328; 1471-0528
• DOI: 10.1111/1471-0528.16013

Summary 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 Pravastatin does not improve maternal plasma sFlt‐1 or placental growth factor levels following a diagnosis of early preterm pre‐eclampsia #clinicaltrial finds. Tweetable Pravastatin does not improve maternal plasma sFlt‐1 or placental growth factor levels following a diagnosis of early preterm pre‐eclampsia #clinicaltrial finds.