[Treatment of pulmonary arterial hypertension]

Treatment of pulmonary arterial hypertension (PAH) attempts to counteract the deleterious effects of pulmonary vasoconstriction, pulmonary vascular remodeling, thrombosis and right heart dysfunction. The development of therapies targeting the endothelial dysfunction (endothelin-receptor antagonists, prostacyclin derivatives, phosphodiesterase type 5 inhibitors) has markedly improved patients' prognosis. Intravenous epoprostenol remains the first line treatment for the most severe patients (NYHA [New York Heart Association] functional class IV). In this situation, initial combination therapy with epoprostenol and either an endothelin-receptor antagonist (ERA) or a phosphodiesterase type 5 inhibitor (PDE5 I), or both should also be discussed. Patients in functional class III should be considered candidates for treatment with either an ERA or a PDE5 I, or a prostanoid. Patients who are in functional class II should be treated with an ERA or a PDE5 I. In the case of inadequate clinical response with a first line therapy, sequential combination therapy should be considered. Combination therapy can include either an ERA plus a PDE5 I,or a prostanoid plus an ERA, or a prostanoid plus a PDE5 I and sometimes a triple therapy. Recommendations in pediatric PAH are equivalent to those proposed in adults. Randomised studies are rare and pharmacokinetics data for available drugs are scarce. The impact of these new therapeutic approaches on long-term survival of patients with PAH is a major challenge in the near future.