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Development of macitentan for the treatment of pulmonary arterial hypertension
Author(s) -
Selej Mona,
Romero Alain J.,
Channick Richard N.,
Clozel Martine
Publication year - 2015
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12856
Subject(s) - endothelin receptor antagonist , medicine , tolerability , pulmonary hypertension , ambrisentan , cardiology , adverse effect , endothelin receptor , bosentan , heart failure , placebo , receptor , alternative medicine , pathology
Pulmonary arterial hypertension (PAH) is a serious, chronic condition that, without early recognition and treatment, leads to progressive right heart failure and death. The dual endothelin receptor antagonist macitentan was designed through a deliberate discovery process to maximize endothelin‐axis blockade while improving adverse‐effect profiles compared with previous compounds. Macitentan's efficacy was demonstrated in an event‐driven morbidity and mortality study of treatment‐naive and background PAH therapy–treated symptomatic patients. Compared to placebo, 10 mg of macitentan significantly reduced the relative risk of morbidity and mortality by 45%, primarily by delaying PAH worsening, most prominently in World Health Organization (WHO) functional class II and III PAH patients. Macitentan reduced the incidence of the composite end point of PAH‐related hospitalizations and mortality and improved WHO FC and exercise capacity (6‐min walk distance). Furthermore, it significantly improved cardiopulmonary hemodynamics and quality of life, and had a favorable safety and tolerability profile. To date, this was the largest and longest prospective trial for PAH. Macitentan, currently the only approved oral PAH treatment shown to be safe and effective in delaying long‐term progression and reducing PAH‐related hospitalizations, has changed treatment paradigms from goal‐directed to long‐term outcome–oriented therapy.