Selexipag for the treatment of pulmonary arterial hypertension

ABSTRACT

Introduction

: Pulmonary arterial hypertension (PAH) is a rare pulmonary vasculopathy. This review focuses on selexipag, a prostacyclin receptor agonist validated for the treatment of PAH.

Areas covered

We review the structure, mechanisms of action, pharmacokinetics, and pharmacodynamics of selexipag. Clinical efficacy and tolerability are discussed using the main clinical trial published for selexipag (GRIPHON) and its post-hoc analysis.

Expert opinion

Selexipag should be added as a triple oral combination therapy in case of insufficient response to oral combination therapy with endothelin receptor antagonist and phosphodiesterase 5 inhibitor. However, selexipag should not replace parenteral prostacyclin in high-risk patients.

KEYWORDS:

• Endothelin receptor antagonist
• guanylate cyclase stimulators
• phosphodiesterase type 5 inhibitor
• pulmonary arterial hypertension
• prostacyclin Pathway
• selexipag

Article highlights

• Pulmonary arterial hypertension (PAH) is a rare pulmonary vasculopathy progressively leading to right heart failure and eventually death.

• The vast majority of patients are not eligible for calcium channel blockers therapy, because of negative acute vasoreactivity testing. They benefit from specific pulmonary vasodilators.

• Selexipag is a prostacyclin receptor agonist that has different pharmacokinetic and pharmacodynamic properties than synthetic prostacyclin (epoprostenol) and prostacyclin analogs (beraprost, iloprost, and treprostinil)

• Selexipag was demonstrated to be effective in improving a composite outcome of morbidity-mortality in adults PAH patients (mainly idiopathic, associated with connective tissue disease and secondary to corrected congenital heart defects) in WHO-FC II and III as a monotherapy, or as a sequential therapy in addition to an endothelin receptor agonist or a phosphodiesterase 5 inhibitor.

• In clinical practice, selexipag is mainly used when patients show insufficient response to an initial oral combination therapy of an endothelin receptor agonist and a phosphodiesterase 5 inhibitor.

• Selexipag is not equivalent to parenteral prostacyclin and is not intended to replace its use in high-risk patients.

• Due to sparse data for pediatric patients, selexipag can be used on a case-by-case basis with prudent selection and close monitoring as we wait for the results of an ongoing randomized controlled trial assessing the dose and efficacy of selexipag in children.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Scientific accuracy review

Actelion provided a scientific accuracy review at the request of the journal editor.

Declaration of interest

M Beghetti reports grants, personal fees, and non-financial support from Actelion, grants and personal fees from Bayer, personal fees from GSK, personal fees from Elililly, personal fees from Orphacare, personal fees from MSD, outside the submitted work. F Lador reports personal fees support from Actelion, OrphaSwiss, and MSD, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.