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Journal Club: Pravastatin in Pregnancy-A few articles

Journal Club: Pravastatin in Pregnancy-A few articles

Pravastatin for the Prevention of Preeclampsia in High-Risk Pregnant Women
Maged M. Costantine, M.D. and Kirsten Cleary, M.D. for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Obstetric-Fetal Pharmacology Research Units Network*

Obstet Gynecol. 2013 February ; 121(2 0 1): .

Abstract
Preeclampsia complicates approximately 3–5% of pregnancies and remains one of the major causes of maternal and neonatal morbidity. It shares pathogenic similarities with adult cardiovascular disease as well as many risk factors. Attempts at prevention of preeclampsia using various supplements and classes of medications have failed or had limited success, and were not convincing enough to lead to widespread adoption of any particular strategy. Contrary to the experience with preeclampsia, prevention of cardiovascular mortality and other cardiovascular events in non-pregnant patients using 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, or statins, is widely accepted. Pravastatin, and other statins, have been shown to reverse various pathophysiological pathways associated with preeclampsia, such as angiogenic imbalance, endothelial injury, inflammation, and oxidative stress. These beneficial effects are likely to contribute substantially to preventing preeclampsia, and provide biological plausibility for the use of pravastatin in this setting. Pravastatin has favorable safety and pharmacokinetic profiles. In addition, animal studies and pregnancy human exposure data do not support teratogenicity claims
for pravastatin. Therefore, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Units Network started a pilot trial to collect maternal-fetal safety data and evaluate pravastatin pharmacokinetics when used as a prophylactic daily treatment in high-risk pregnant women (ClinicalTrials.gov identifier NCT01717586).

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Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy

Eleftheria Lefkou,Apostolos Mamopoulos,Themistoklis Dagklis,Christos Vosnakis, David Rousso, and Guillermina Girardi

J Clin Invest. 2016;126(8):2933–2940. doi:10.1172/JCI86957.

BACKGROUND. Administration of conventional antithrombotic treatment (low-dose aspirin plus low–molecular weight heparin [LDA+LMWH]) for obstetric antiphospholipid syndrome (APS) does not prevent life-threatening placenta insufficiency–associated complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR) in 20% of patients. Statins have been linked to improved pregnancy outcomes in mouse models of PE and APS, possibly due to their protective effects on endothelium. Here, we investigated the use of pravastatin in LDA+LMWH-refractory APS in patients at an increased risk of adverse pregnancy outcomes.

METHODS. We studied 21 pregnant women with APS who developed PE and/or IUGR during treatment with LDA+LMWH. A control group of 10 patients received only LDA+LMWH. Eleven patients received pravastatin (20 mg/d) in addition to LDA+LMWH at the onset of PE and/or IUGR. Uteroplacental blood hemodynamics, progression of PE features (hypertension and proteinuria), and fetal/neonatal outcomes were evaluated.

RESULTS. In the control group, all deliveries occurred preterm and only 6 of 11 neonates survived. Of the 6 surviving neonates, 3 showed abnormal development. Patients who received both pravastatin and LDA+LMWH exhibited increased placental blood flow and improvements in PE features. These beneficial effects were observed as early as 10 days after pravastatin treatment onset. Pravastatin treatment combined with LDA+LMWH was also associated with live births that occurred close to full term in all patients.
CONCLUSION. The present study suggests that pravastatin may improve pregnancy outcomes in women with refractory obstetric APS when taken at the onset of PE or IUGR until the end of pregnancy.

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