How a Most Unlikely Drug Changed the Outcome of Pulmonary Arterial Hypertension

Epoprostenol is a prostaglandin that was first identified by investigators in 1976 and found to be a potent vasodilator and inhibiter of platelet aggregation, initially in animal studies and subsequently in humans. Based on these properties epoprostenol, which has a short half-life of several minutes in vivo requiring continuous intravenous infusion, was administered to patients with pulmonary arterial hypertension (PAH) and found to decrease pulmonary vascular resistance (PVR) during acute vasodilator testing. Investigators then studied the effects of long-term infusion of epoprostenol and observed sustained hemodynamic and clinical improvement, albeit with persistent elevation of pulmonary artery pressure and PVR. The results of a randomized multicenter study confirmed the benefit of epoprostenol, including improved survival, in patients with PAH leading to FDA approval in 1995. Before this, there was no effective therapy for the vast majority of patients with PAH. A number of other less complicated and safer medications have subsequently been approved for the treatment of patients with PAH. However, nearly 30 years after approval, despite the complexity and risks of continuous intravenous therapy, epoprostenol remains the most effective treatment for PAH.