Macitentan for the treatment of pulmonary arterial hypertension

Abstract

Macitentan is a novel dual endothelin receptor antagonist recently approved for the treatment of symptomatic pulmonary arterial hypertension (PAH). Compared to other endothelin receptor antagonists, in vitro and in vivo studies have demonstrated that macitentan has improved tissue targeting, a longer duration of action and an improved safety profile. Macitentan is available as a once daily oral medication and has been well tolerated in clinical trials. The recently published Study with an Endothelin Receptor Antagonist in PAH to Improve cliNical Outcomes (SERAPHIN), which was the first event-driven trial ever done in PAH, also demonstrated the benefit of macitentan on reducing the likelihood of a composite endpoint of morbidity and mortality events without a significant difference in mortality.

Keywords::

• endothelin receptor antagonist
• macitentan
• pulmonary arterial hypertension

Financial & competing interests disclosure

R Channick has received research grants from Actelion pharmaceuticals and has served as a consultant for Actelion. H DuBrock has no conflicts of interest to disclose. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pulmonary arterial hypertension (PAH) is a disease characterized by vasoconstriction and vascular remodeling that is associated with significant morbidity and mortality.

• Current treatment options target the endothelin, nitric oxide and prostacyclin pathways but disease progression often occurs despite treatment.

• Bosentan and ambrisentan are two endothelin receptor antagonists approved for the treatment of pulmonary arterial hypertension but both are associated with significant adverse effects including aminotransferase elevation and edema, respectively.

• Macitentan is a novel dual endothelin receptor antagonist with increased potency and tissue targeting and an improved side effect profile compared with other endothelin receptor antagonists.

• Macitentan was recently studied in the largest event-driven study in pulmonary arterial hypertension to date and was found to delay progression of disease and decrease time to a composite end point of morbidity and mortality events.

• Macitentan is well tolerated; the most common side effects include peripheral edema (18.2%), nasopharyngitis (14%), headache (13.6%) and anemia (13.2%).

Notes