Pharmacotherapy for idiopathic pulmonary arterial hypertension during the past 25 years.

OBJECTIVE To review the current pharmacotherapy for idiopathic pulmonary arterial hypertension (IPAH). METHODS A search of the primary literature was conducted by using MEDLINE, the National Institutes of Health medical research Web site (www.clinicaltrials.gov), and the United States Food and Drug Administration's Center for Drug Evaluation and Research Web site (www.fda.gov/cder). RESULTS Until the early 1980s, conventional therapy for IPAH consisted of anticoagulation, diuretics, digitalis extracts, and supplemental oxygen, yet the 5-year mortality rate remained at 66%. Calcium channel blocker therapy was introduced with the hope that it would improve survival in patients with IPAH, but it was found to be effective in only approximately 25% of patients. In 1996, intravenous epoprostenol was the first drug to show long-term benefit on hemodynamics, exercise capacity, and survival. However, administration of epoprostenol requires a permanently indwelling central venous catheter, and tachyphylaxis is common, necessitating continuous dosage escalations. Subsequently, treprostinil, a prostacyclin analog of epoprostenol that can be administered by continuous subcutaneous infusion, was introduced, followed by aerosolized iloprost, a prostacyclin analog for inhalation. An increasing understanding of the multiple pathogeneses of IPAH led to the discovery of another target for drug therapy, and bosentan, an orally administered agent, became the first endothelin-receptor antagonist approved for treatment of IPAH. Most recently, the phosphodiesterase inhibitor, sildenafil, has received approval from the United States Food and Drug Administration for the treatment of IPAH. CONCLUSION Recently developed pharmacotherapies offer greater effectiveness and safety than traditional agents for the treatment of IPAH.