Positioning Newer Agents: Riociguat, Selexipag, and Oral Treprostinil in the Current Landscape

Abstract

The availability of newer oral agents for therapy of pulmonary arterial hypertension entails both opportunity and uncertainty. There is the opportunity for less intrusive therapy and the potential to further lessen risk of disease progression, but there is also uncertainty regarding optimal role of these agents, concern about their expense, and risk of preventable deterioration if these agents are used in settings that clearly warrant parenteral prostanoids. Among the newer agents, the evidence is strongest for the use of the prostacyclin receptor agonist selexipag, which has been shown to reduce events in functional class II and III patients, even in the setting of background therapy with a phosphodiesterase type 5 (PDE5) inhibitor and an endothelin receptor antagonist. Riociguat is a soluble guanylate cyclase stimulator that has been shown to be beneficial, including in combination with an endothelin receptor antagonist, and may be a useful alternative to a PDE5 inhibitor in properly selected patients. It has also been shown to be beneficial in inoperable or residual thromboembolic pulmonary hypertension. Oral treprostinil has been shown to improve 6-minute walk distance as monotherapy, and has been used to transition from inhaled or parenteral treprostinil in carefully selected patients also on other agents. Herein we discuss the mechanisms of action, side effect profiles, and clinical trial data for these agents, followed by a practical approach to their use, integrating the available data with real-world experience.