PHARMACOLOGICAL UPDATE

Summary
Treatment of pulmonary arterial hypertension with macitentan, dual endothelin receptor antagonist
Valentina M. Bichara, Raúl J. Bevacqua

Pulmonary arterial hypertension (PAH) is a disease characterized by progressive remodeling of the distal pulmonary arteries, resulting in the loss of vascular cross-sectional area and elevated pulmonary vascular resistance. Without intervention, PAH is usually progressive and leads to right heart failure and death. The development of drugs that specifically target the pathways involved in the pathogenesis of the disease has led to improvements in the quality of life and clinical outcomes in patients with PAH.
Macitentan, a dual endothelin receptor antagonist (ERA) developed by modifying the structure of bosentan to increase efficacy and safety, is approved for the treatment of PAH. The SERAPHIN trial showed a risk reduction of a morbidity or mortality event by 45% during the time of treatment compared to placebo. The positive effect on the primary endpoint was observed whether or not the patient was already on PAH therapy. There has been no direct comparison between macitentan and other ERAs, which were approved based on improved exercise capacity, but preclinical and clinical data suggest better pharmacological and safety profiles.
This update presents evidence of macitentan's superiority for the treatment of PAH, compared to other ERAs, and data from available clinical trials, as well as possible future strategies.

Keywords: Pulmonary arterial hypertension - Endothelin receptor antagonist - Macitentan