Practice Update: Cardiology

Low-molecular-weight heparin improves endothelial function in pregnant women at high risk of preeclampsia AMERICAN HEART ASSOCIATION ANNUAL SCIENTIFIC SESSIONS 26

J ohn Kingdom, MD, of Mount Sinai Hospital, Toronto, Ontario, Canada, explained that preeclampsia is a hypertensive disorder of pregnancy characterised by new-onset hypertension with evidence of organ injury. The disorder affects 2–8% of pregnancies worldwide. The majority of women with preeclampsia present clinically near term with favourable maternal and infant outcomes. A subset, however, develop severe disease characterised by the need for preterm delivery, typically before 34 weeks of gestation due to end- organ injury, severe hypertension, or intrauterine growth restriction. Women with severe preeclampsia demonstrate significant cardiovascular impairment during pregnancy and the immediate postpartum period, as well as a higher risk of cardiovascular disease later in life. Given the significant short-and long- term maternal cardiovascular effects of preeclampsia, elucidating its pathogenesis has been of interest in recent years. Yet the most effective pharmacologic therapy to prevent preeclampsia in screen-positive women beyond aspirin has not been established. Clinical symptoms typically resolve only on delivery. Low-molecular-weight heparin has been evaluated for the prevention of various placenta-mediated pregnancy complications, including severe preeclampsia and recurrent miscarriage. Multiple trials and systematic

For the first time, low-molecular weight heparin has been shown to improve maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability, reported a randomised, prospective trial at AHA 2016.

reviews have concluded that low-molecular- weight heparin reduces the incidence of recurrent severe preeclampsia in high- risk women, as well as perinatal mortality, preterm birth, and infant birth weight <10th percentile for gestational age. Others have demonstrated no treatment effect. As the majority of trials have consisted of clinical endpoints, the mechanism of action of low-molecular-weight heparin for the possible prevention of severe preeclampsia is unknown. Evidence suggests that observed beneficial effects do not result from heparin’s anticoagulant actions within the placenta. An alternative hypothesis is that low- molecular-weight heparin exerts vascular actions in the maternal compartment. These actions are thought to reverse the systemic vascular dysfunction characteristic of preeclampsia. Trials in patients with coronary artery disease have determined that low-molecular-weight heparin demonstrates beneficial endothelial effects, possibly through increased bioavailability of nitric oxide. Dr Kingdom and colleagues set out to investigate the cardiovascular effects of low- molecular-weight heparin in pregnant women at high risk of preeclampsia. Twenty-five pregnant women at high risk of preeclampsia and 20 low-risk pregnant controls at 22–26 weeks of gestation underwent baseline cardiovascular

PRACTICEUPDATE CARDIOLOGY