Macitentan for the treatment of pulmonary arterial hypertension

To review the pharmacology, safety, and efficacy of macitentan.

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

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

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.

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.