Overview of treprostinil sodium for the treatment of pulmonary arterial hypertension.
Pulmonary arterial hypertension is a life-threatening disorder that refers to a group of diseases characterized by an abnormal elevation of the blood pressure within the pulmonary circulation due to a vasculopathy of the pulmonary microcirculation (1). If left untreated, the overall prognosis of pulmonary arterial hypertension is poor, with a 5-year survival rate of 34%. The most common cause of death is progressive right-sided heart failure (2). There is no pharmacologic cure for pulmonary arterial hypertension, and a team approach is required for the proper care of these patients (3). Treatment is directed at improving clinical symptoms, increasing exercise tolerance and extending survival. Until just a few years ago, standard treatment options for the treatment of pulmonary arterial hypertension were limited and included coumarin derivatives, calcium channel blockers, diuretics, digoxin and oxygen supplementation (4). In the last decade, the therapeutic options for pulmonary arterial hypertension have made considerable advances. In at least three major randomized controlled trials, the continuous intravenous infusion of epoprostenol, a synthetic salt of prostacyclin with potent vasodilatory ability, has been shown to improve exercise tolerance, hemodynamics, survival and quality of life in patients with New York Heart Association (NYHA) functional classes III and IV with either primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma (5-9). Epoprostenol has now become a mainstay therapy in the long-term treatment of primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma. Nevertheless, epoprostenol is far from an ideal form of therapy. Issues such as the short half-life of the drug, need for continuous central intravenous access and significant side effects have led to the development of more stable prostacyclin analogues as alternative therapies for primary pulmonary hypertension. These alternative therapies include iloprost (inhaled delivery) and treprostinil (subcutaneous delivery). As a result, the Food and Drug Administration (FDA) recently approved treprostinil for the treatment of pulmonary arterial hypertension in patients with NYHA classes II-IV. This review will offer a discussion of the basic pharmacology of treprostinil, its similarities to and differences from epoprostenol, the animal studies as well as the initial investigational studies leading to its FDA approval, and clinical uses of the drug alone or in combination with newer therapies directed at pulmonary arterial hypertension developed over the last decade.
Budev
Marie M
MM
Department of Pulmonary and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. minaio@ccf.org
Minai
Omar A
OA
Arroliga
Alejandro C
AC
D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D011464:Epoprostenol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008168:Lung / Q000098:blood supply; D016032:Randomized Controlled Trials as Topic
D000959:Antihypertensive Agents; D011464:Epoprostenol; C427248:treprostinil