Pulmonary artery pressure-directed therapies in pulmonary arterial hypertension?

Pulmonary arterial hypertension is a rare dyspnea-fatigue syndrome defined by an increase in mean pulmonary artery pressure above 20 mmHg combined with an increase in pulmonary vascular resistance higher than 2 Wood units. The condition is of poor prognosis and still incurable in spite of progress achieved in recent decades. The approach is currently optimized by multi-drug combinations titrated on serial risk assessments using recently validated scores. In this issue of Vascular Pharmacology argument is made based on retrospective registry data from three reference centers in favor of initial multi-drug therapies including a parenteral prostanoid dosed to decrease mPAP to normal. This objective was achieved in only a minority of patients, but improved outcome was demonstrated when mPAP can be brought to below 35 mmHg. This data suggest that pulmonary artery pressure-directed multi-drug therapies in PAH may reverse right heart remodeling and limit progression, or even reverse pulmonary vascular disease. However, further studies are needed to validate mPAP as a primary endpoint in PAH drug trials. In the meantime, aggressive initial prescription of parenteral prostanoids combined with one or two oral drugs targeting the pulmonary circulation under careful clinical, imaging and hemodynamic follow-up may be the best therapeutic strategy.