Pravastatin for prevention of HELLP syndrome

Abstract

Rationale:Pravastatin has emerged for prevention and treatment of preeclampsia; no reports are available on pravastatin and HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome.Patient concerns:The first pregnancy necessitated termination of pregnancy at gestational age (GA) 20+5 for HELLP. Intrauterine fetal death at GA 22+5 occurred in the second pregnancy, whilst on temporizing management of HELLP.Diagnoses:Severe, recurrent early-onset HELLP syndrome.Interventions:In her fourth pregnancy, pravastatin was commenced at GA 13.Outcomes:The course of pregnancy was uncomplicated, and a healthy, appropriate for gestational age fetus was delivered at term.Lessons:Pravastatin may be effective in prevention of HELLP. The hepatic uptake may be of particular advantage.

Modelling preeclampsia: a comparative analysis of the common human trophoblast cell lines

“…In a pilot randomized controlled pharmacokinetic study of high‐risk pregnancies, Costantine et al 63 showed promising, although non‐significant, sFlt‐1 and sEng lowering in 10 women who received 10 mg pravastatin daily (vs. 10 placebo subjects) starting from early second trimester. A few other small trials and case studies also reported encouraging data 64‐66 . However, the recent randomized controlled trial of “Statins to Ameliorate Pre‐Eclampsia (StAmP)” found no evidence of sFlt‐1 reduction in 30 women with early‐onset preeclampsia who received 40 mg pravastatin daily in the third trimester (vs. 32 placebo subjects) 25 .…”

“…A few other small trials and case studies also reported encouraging data. [64][65][66] However, the recent randomized controlled trial of "Statins to Ameliorate Pre-Eclampsia (StAmP)" found no evidence of sFlt-1 reduction in 30 women with early-onset preeclampsia who received 40 mg pravastatin daily in the third trimester (vs. 32 placebo subjects). 25 Intriguingly, in most studies with cultured human primary trophoblasts or villous explants, pravastatin appeared to reduce sFlt-1 and sEng only at sub-millimolar to millimolar concentrations, [67][68][69][70] substantially higher than the sub-micromolar plasma concentrations achievable in humans taking the drug.…”

Ferroptosis and Its Emerging Role in Pre-Eclampsia

“…They may also interfere with cell proliferation, growth, and metabolism and protein glycosylation, which all play important roles in normal placental development. Statins may also disrupt the placenta by expressing peroxisome proliferator-activated receptor γ and inhibit trophoblast invasion [ 182 ]. In a patient with poor obstetric outcomes, Otten et al [ 183 ] administered 10 mg of pravastatin daily beginning in the second trimester of pregnancy, achieving a normal pregnancy and full-term delivery of a healthy neonate suitable for gestational age in a patient with a history of severe, early-onset, recurrent HELLP syndrome.…”

Fetal toxicity associated with statins: A systematic review and meta-analysis

“…Five studies were performed on pregnant women with hypercholesterolemia 22,[25][26][27][28] and three studies were performed on women who had preeclampsia or were at high risk for it 24,29,30 . According to the methodology, the studies included nine cohort articles 16,22,23,25,28,[31][32][33][34] , six case reports 26,27,30,[35][36][37] , six case series 29,[38][39][40][41][42] , one clinical trial 24 , and one population-based case-referent study 43 . The studies were published from 1992 to 2018.…”