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A Focus on Macitentan in the Treatment of Pulmonary Arterial Hypertension
Author(s) -
Bedan Martin,
Grimm Daniela,
Wehland Markus,
Simonsen Ulf,
Infanger Manfred,
Krüger Marcus
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13033
Subject(s) - bosentan , ambrisentan , endothelin receptor antagonist , medicine , pharmacology , endothelin receptor , cardiology , receptor
The approval of macitentan has increased the number of pharmacological treatments of pulmonary arterial hypertension ( PAH ). Here, we review the effect on PAH of macitentan compared to other endothelin receptor antagonists. Drugs targeting the endothelin ( ET ) pathway include the selective ET A receptor antagonist ambrisentan, the ET A / ET B receptor antagonists, bosentan and macitentan, which were recently approved for PAH treatment. Macitentan exhibits higher antagonistic potency than bosentan and ambrisentan in pulmonary smooth muscle cells. Compared to ambrisentan and bosentan, macitentan has a longer duration of action, reflected by the longer half‐life, as well as pharmacodynamics attributed to its active metabolite, ACT ‐132577. The efficacy of macitentan on PAH was investigated in the phase III SERAPHIN trial ( NCT 00660179). Macitentan significantly reduced morbidity and mortality. It improved the 6‐min. walk distance (6 MWD ) among PAH patients. In the AMB ‐320/321‐E ( NCT 00578786) study, ambrisentan improved exercise capacity. In the EARLY study ( NCT 00091715), bosentan showed improvements in 6 MWD which were not statistically significant. Bosentan had an effect on PAH in patients with Eisenmenger syndrome ( ES ) in the BREATHE ‐5 study ( NCT 00367770), while macitentan did not improve 6 MWD in these patients, but there are differences regarding study size and functional class, and that 30% of the patients treated with macitentan were already in treatment with a phosphodiesterase type 5 inhibitor. Macitentan revealed a lower risk of developing peripheral oedema and hepatotoxicity in the SERAPHIN study. In summary, macitentan has an efficiency comparable to bosentan and ambrisentan in the treatment of PAH . Patients treated with macitentan exhibited less adverse effects compared to bosentan and ambrisentan. In patients with PAH associated with ES , the trials with bosentan and macitentan do not seem comparable, and it needs to be clarified whether these drugs are effective when administered as part of a combination treatment in this condition.