Macitentan for the treatment of pulmonary arterial hypertension.
OBJECTIVE
To review the pharmacology, safety, and efficacy of macitentan.


METHODS
PubMed, EMBASE, and ClinicalTrials.gov were searched using the terms macitentan and ACT-064992.


METHODS
Phase II and III trials were reviewed in our primary analysis; data from phase I trials and other studies were reported as applicable.


RESULTS
Macitentan is a dual endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH). Current treatment options for PAH include 2 other ERAs, phosphodiesterase type 5 inhibitors, prostanoids, and calcium channel blockers. Recently published guidelines do not assert a preference for individual agents. Two trials evaluated the safety and efficacy of macitentan. The phase II study was a 12-month placebo-controlled trial involving patients with idiopathic pulmonary fibrosis; the primary end point was change in forced vital capacity. No significant treatment effect was observed. The phase III study was a placebo-controlled trial involving patients with PAH. The primary end point was time to first occurrence of a composite of outcomes, including all-cause death and PAH worsening. Over a median period of 115 weeks, macitentan 10 mg and 3 mg daily significantly reduced morbidity and mortality. Commonly reported adverse effects included worsening of PAH, peripheral edema, upper-respiratory-tract infection, and anemia.


CONCLUSIONS
Macitentan represents the latest addition to the PAH armamentarium. Compared with other ERAs, clinical advantages may include fewer contraindications, use in hepatic impairment, and once-daily administration. However, further comparative studies are necessary to ascertain its place in therapy.
University at Buffalo, The State University of New York, NY, USA.
Irene S
IS
Hong
Holly V
HV
Coe
Linda M
LM
Catanzaro
D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy; D011743:Pyrimidines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
D065128:Endothelin Receptor Antagonists; D011743:Pyrimidines; D013449:Sulfonamides; C533860:macitentan
ACT-064992; endothelin receptor antagonist; macitentan; pulmonary arterial hypertension