New Oral Drugs for Pulmonary Arterial Hypertension: Macitentan, Riociguat, and Treprostinil
In 2013, the US Food and Drug Administration (FDA) approved 3 new oral drugs for the treatment of pulmonary arterial hypertension (PAH; World Health Organization [WHO] Group 1 pulmonary hypertension [PH]). These include the endothelin receptor antagonist macitentan, the soluble guanylate cyclase stimulator riociguat, and the prostacyclin analogue treprostinil. In addition, riociguat was approved for the treatment of patients with inoperable or postsurgery recurrent or persistent chronic thromboembolic PH (CTEPH; WHO Group 4 PH). The approval of these drugs has several important clinical implications: first, in a disease where many of the currently available treatments are complicated by significant side effects and/or complex administration regimens, the availability of new oral drugs clearly represents a valuable addition to the armamentarium. Second, the macitentan study was the first long-term, event-driven trial to be published in the PAH field, making the results more robust and paving the way for improved clinical trial design in the future. Third, riociguat is the first FDA-approved medical treatment regimen for selected CTEPH patients, thus providing a critical treatment option for patients with inoperable or recurrent/persistent CTEPH. Lastly, the approval of oral treprostinil made this drug the first oral prostacyclin analogue to be available in the United States. In this article, the authors will discuss the mechanisms of action of macitentan, riociguat, and oral treprostinil; review the landmark trials that led to the FDA approval of these drugs, and discuss their clinical use.