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 |
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Pages (from-to) | 478-488 |
Number of pages | 11 |
Journal | BJOG: An International Journal of Obstetrics & Gynaecology |
Volume | 127 |
Issue number | 4 |
Early online date | 12 Nov 2019 |
DOIs | |
Publication status | Published - Mar 2020 |
Keywords
- anti‐angiogenic factor
- double‐blind
- perinatal mortality
- placebo‐controlled
- pravastatin
- pre‐eclampsia
- randomized trial
- statin
- pre-eclampsia
- randomised trial
- placebo-controlled
- Anti-angiogenic factor
- double-blind
- 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
ASJC Scopus subject areas
- Obstetrics and Gynaecology