Treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries. It induces a fixed pulmonary arterial obstruction, persistent elevation of pulmonary arterial resistance, and eventually right heart failure. Conventional therapy is based on simple measures (exercise limitation) and nonspecific treatments (warfarin, diuretics, and oxygen). Pure vasodilators, such as calcium channel blockers, are effective only in a minority of patients who have an acute response to vasodilator testing. Intravenous prostacyclin (epoprostenol) and endothelin receptor blockers have vasodilator and antiproliferative properties. Epoprostenol therapy has significantly improved PAH prognosis and remains the first-line treatment for patients with the most severe disease. Bosentan is an interesting first-line treatment for NYHA functional class III patients. Availability of novel specific drugs (endothelin receptor type A antagonists, prostacyclin analogues, type 5 phosphodiesterase inhibitors) is opening new perspectives in PAH treatment. The long-term benefit of these drugs remains to be evaluated and their respective place in treatment of these patients is still uncertain. The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.

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