Selexipag for Treatment of Pulmonary Arterial Hypertension

Study Questions:

What are the safety and efficacy of selexipag in patients with pulmonary arterial hypertension (PAH) not receiving therapy at baseline and those who are already receiving one or two therapies for the disease at baseline?


The GRIPHON (Prostacyclin [PGI2] Receptor Agonist in Pulmonary Arterial Hypertension) study was a multicenter, double-blind, randomized, parallel-group, placebo-controlled phase 3 study. The study population included patients 18-75 years of age who had idiopathic or heritable PAH or PAH associated with human immunodeficiency virus infection, drug use or toxin exposure, connective tissue disease, or repaired congenital systemic-to-pulmonary shunts. Patients who were not receiving treatment for PAH and those who were receiving an endothelin-receptor antagonist, a phosphodiesterase-5 inhibitor, or both at a dose that had been stable for at least 3 months were eligible. Patients were randomized to receive placebo or selexipag in individualized doses. The primary endpoint was a composite of death or complication related to PAH, whichever occurred first.


A total of 1,156 patients were enrolled and randomly assigned to receive placebo (n = 582) or selexipag (n = 574). Overall, 397 patients had a primary endpoint event (242 patients [41.6%] in the placebo group and 155 patients [27.0%] in the selexipag group). The hazard ratio for a primary endpoint event in the selexipag group was 0.60 (99% confidence interval [CI], 0.46-0.78; p < 0.001). Disease progression and hospitalization accounted for 81.9% of the events. By the end of the study, death from any cause had occurred in 105 patients (18.0%) in the placebo group and in 100 patients (17.4%) in the selexipag group (hazard ratio in the selexipag group, 0.97; 95% confidence interval, 0.74-1.28; p = 0.42). Overall, 7.1% of patients in the placebo group and 14.3% of patients in the selexipag group discontinued their assigned regimen prematurely because of adverse events. The most common side effects in the selexipag group were headache, diarrhea, and nausea.


Among patients with PAH, the risk of the primary composite endpoint of death or a complication related to PAH was significantly lower among patients who received selexipag than among those who received placebo. There was no mortality difference between the two study assignments.


Selexipag is an oral selective IP prostacyclin-receptor agonist that has been shown to be beneficial in the treatment of PAH in phase 2 trials. Now this phase 3 trial establishes the safety and efficacy of this agent, compared to placebo. While no mortality reduction was observed, the risk of the primary endpoint (composite of death from any cause or a complication related to PAH) was significantly lower in the group receiving selexipag compared to placebo.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Congenital Heart Disease, CHD and Pediatrics and Prevention, Lipid Metabolism, Pulmonary Hypertension, Hypertension

Keywords: Connective Tissue Diseases, Endothelin Receptor Antagonists, Epoprostenol, Heart Defects, Congenital, HIV Infections, Hypertension, Hypertension, Pulmonary, Phosphodiesterase 5 Inhibitors, Prostaglandins I, Receptors, Epoprostenol

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