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Published online: 25 July 2014
© Springer International Publishing Switzerland 2014
Abstract Macitentan (Opsumit®) is an orally active, dual endothelin receptor antagonist (ERA) with tissue targeting properties. Macitentan was approved recently in the EU (as monotherapy or combination therapy) for the long-term treatment of pulmonary arterial hypertension (PAH) in adults of WHO functional class II or III, and in the USA for the treatment of PAH (WHO group I) to delay disease progression and reduce hospitalization for PAH. This article reviews the pharmacological properties, efficacy and tolerability data relevant to the use of macitentan in this indication. Treatment with macitentan 10 mg once daily significantly reduced the risk for the primary composite endpoint of morbidity and mortality in patients with PAH (mostly WHO functional class II or III) in the large, randomized, placebo-controlled SERAPHIN study. Other efficacy outcomes, including exercise capacity, haemodynamic parameters and health-related quality of life also improved significantly with macitentan relative to placebo. Macitentan was generally well tolerated in this study. As with other ERAs, haemoglobin levels decreased with macitentan therapy; however, these were not progressive and stabilized following longer-term treatment. Although comparative studies are needed to definitively position macitentan with respect to other approved agents, current evidence suggests that macitentan is a useful treatment option for initial therapy in patients with WHO functional class II or III PAH, which has the potential advantage of once-daily administration.
1 Introduction
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by the presence of pre- capillary pulmonary hypertension (PH; defined as pul- monary arterial pressure of >25 mmHg, pulmonary wedge pressure of <15 mmHg, and normal or reduced cardiac output) in the absence of other causes of pre-capillary PH (e.g. lung diseases or chronic thromboembolic PH) [1, 2], The most recent estimates of PAH in Europe reported an annual incidence of 2.4 cases/million adults in France (in 2002-2003) [3] and 7.6 cases/million population in Scot- land (in 1986-2001) [4]
PAH (or group 1 PH) can be classified according to its underlying aetiology (Table 1) [5] and severity (Table 2) [1]. The disease results from functional and structural changes in the pulmonary vasculature, leading to increased pulmonary vascular resistance, right ventricular failure and subsequently death [6-8]. Imbalances in three main bio- logical...