Treatments for pulmonary arterial hypertension

PURPOSE: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis and vascular remodeling of small pulmonary arteries inducing a fixed pulmonary arterial obstruction and persistent elevation of pulmonary arterial resistance. Conventional treatment is based on simple measures (exercise limitation) and non-specific drugs (warfarine, diuretics, oxygen). CURRENT KNOWLEDGE AND KEY POINTS: Pure vasodilators like calcium channel antagonists have little or no effect on the vast majority of patients, presumably because fixed pulmonary arteriopathy predominate over vasoconstriction. Intravenous prostacyclin (epoprostenol) and endothelin receptor antagonists have vasodilator and antiproliferative properties. Epoprostenol therapy has resulted in significant improvements in prognosis of this disease and this drug remains the first-line treatment of the most severe patients. 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) open new perspectives in treatment of PAH. The long-term benefit of these drugs remains to be evaluated and their respective place in treatment of these patients is still uncertain. We here present the different therapeutic alternatives available in the PAH and propose an algorithm for treatment of these patients. FUTURE PROSPECTS AND PROJECTS: The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.