The Complicated Question of Anticoagulation in Pulmonary Arterial Hypertension: Time to Get Some Simple Answers

Abstract

According to Dr Seuss, “Sometimes the questions are complicated and the answers are simple.” However, when practitioners are asked if anticoagulation is beneficial in pulmonary arterial hypertension (PAH), it is the question that is simple and the answer that is quite complicated. The histology of PAH is characterized by plexiform lesions, vasoconstriction, medial hypertrophy, intimal hyperplasia, perivascular inflammation, and thrombotic lesions within the pulmonary vasculature. The aetiology of these pathologic lesions remains unclear but has been associated with drug exposures, genetic mutations, and other systemic diseases including cirrhosis, HIV, and collagen vascular diseases. Despite the diverse risk factors for the development of PAH, the therapeutic options currently available have focused on pulmonary vasodilation and improvement in right ventricular function. Randomized controlled trials (RCTs) of antiinflammatory and antiproliferative agents have failed to show clinical benefit or decrease the vascular remodelling seen in PAH. Although pulmonary vasodilators have contributed to an improved prognosis in PAH, 1-year mortality rates remain considerable at 7%-17%. Additionally, mortality differs between phenotypes of PAH, and most particularly is worse in scleroderma-associated PAH. In this setting, efforts to define optimum pharmacotherapy in PAH and individualize therapy based on clinical phenotype are important tasks facing PAH providers. One potential therapeutic approach that has remained somewhat controversial is the use of warfarin and anticoagulation in PAH. In 1992, Rich and colleagues found survival was significantly better in patients given anticoagulation when concurrent therapies with calcium channel blockers were examined. Although these patients were not randomized nor was anticoagulation the primary intervention,