Oral Prostacyclin Therapy for Pulmonary Arterial Hypertension

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Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and cellular proliferation that leads to narrowing and obstruction of small pulmonary arteries. The arteriopathy is clinically manifest as increased pulmonary vascular resistance and elevation of pulmonary arterial pressures. PAH is considered a progressive vasculopathy that ultimately leads to right heart failure and death. Although there is no cure for PAH, current pharmacological therapies have improved morbidity, and in some cases, mortality. The current 3-year survival for patients with PAH managed with state-of-the-art multiple drug therapy remains troubling at ≈58%.1 This is slightly better than in the 1980s, when there were no approved treatments. Article see p 624 In PAH endothelial dysfunction and platelet activation causes an imbalance of arachidonic acid metabolites with reduced prostacyclin levels and increased thromboxane A2 production. Prostacyclin has both vasodilatory and antiproliferative affects on vascular smooth muscle and inhibits platelet aggregation. Prostacyclin synthase levels are decreased in pulmonary arteries of patients with PAH.2 An imbalance between these two arachidonic acid metabolites favoring thromboxane A2 plays an important role in the pathogenesis of PAH.3 This imbalance is addressed by the exogenous administration of prostanoids as therapy in advanced PAH. Epoprostenol was the first prostacyclin used in the treatment of PAH. Intravenous epoprostenol improves hemodynamics, functional capacity, and survival.4–7 The second-generation prostanoid, Treprostinil, which has a considerably longer half-life (4.5 hours versus 4–6 minutes for epoprostenol),8 can be administered subcutaneously, intravenously, or by inhalation, and also improves pulmonary hemodynamics, symptoms, exercise capacity, and survival in PAH.9–11 Prostacyclin remains a mainstay of PAH therapy and is the only therapy with a proven survival …