Macitentan in pulmonary arterial hypertension: The SERAPHIN trial.

Karim Said

doi:10.5339/gcsp.2014.20

Abstract

Major limitations of pulmonary arterial hypertension (PAH) drug trials include the small number of enrolled patients, short term follow up (12-16 weeks), and lack of morbidity and mortality primary endpoints. The recently published SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial represents an important landmark in the history of clinical trials in PAH being the largest and longest clinical study conducted thus far in PAH patients with morbidity and mortality events as primary endpoint. SERAPHIN trial investigated whether long-term treatment with the new endothelin receptor antagonist macitentan would reduce the risk of mortality and morbidity in PAH patients.

Highlights

Current clinical research in pulmonary arterial hypertension (PAH) focuses on the development of more potent and less toxic drugs that target pathophysiologic pathways known to be important in PAH with special emphasis on endothelin, nitric oxide and prostacyclin pathways
Of interest are the interactions of bosentan with sildenafil, a frequently used combination therapy, where sildenafil plasma levels are reduced by about 50% while bosentan concentrations rise by approximately 50%
The results showed that over the study period macitentan 10 mg reduced the risk of primary end point by 45% ( p, 0.0001) compared with those who received placebo

Summary

Introduction

Current clinical research in pulmonary arterial hypertension (PAH) focuses on the development of more potent and less toxic drugs that target pathophysiologic pathways known to be important in PAH with special emphasis on endothelin, nitric oxide and prostacyclin pathways.Endothelin is one of the most potent vasoconstrictor ever identified with additional proliferative and profibrotic activities.

Results

Conclusion