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

J Clin Invest. 2016 Aug 1;126(8):2933-40. doi: 10.1172/JCI86957. Epub 2016 Jul 25.


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.

MeSH terms

  • Adult
  • Antiphospholipid Syndrome / drug therapy*
  • Endothelium / metabolism
  • Enoxaparin / administration & dosage
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Gestational Age
  • Hemodynamics
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Pravastatin / administration & dosage*
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Outcome*
  • Risk Factors
  • Tinzaparin
  • Uterine Artery / pathology


  • Enoxaparin
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Tinzaparin
  • Pravastatin