(426) - Value of Cardiopulmonary Exercise Testing for Prediction of Outcomes in Ambulatory Patients With Dilated Cardiomyopathy

Abstract

s S163 7Hannover Medical School and German Center of Lung Research, Hannover, Germany; 8Medical University of Vienna, Vienna, Austria; 9University of Michigan Health System, Ann Arbor, MN; 10University of California, San Diego, CA; 11Hopital Universitaire de Bicetre, Paris, France; 12Cedars-Sinai Medical Center, Los Angeles, CA. Purpose: Selexipag, an orally available, selective IP receptor agonist targeting the prostacyclin pathway, is chemically and pharmacologically distinct from prostanoids. The GRIPHON trial evaluated the long-term effect of selexipag on morbidity/mortality (M/M) as well as tolerability and safety in patients with pulmonary arterial hypertension (PAH). Methods: In this multicenter, double-blind, placebo-controlled, phase 3 study PAH patients (18-75 years) were randomized 1:1 to placebo or selexipag. Study drug was titrated to an individual highest tolerated dose (from 200 to 1600 μg b.i.d.). Stable background PAH therapy with endothelin receptor antagonists (ERA) and/or phosphodiesterase-5 inhibitors (PDE-5i) was allowed. The primary endpoint was the time from randomization to first M/M event up to the end of treatment, defined as either disease progression (based on 15% decrease in 6-minute walk, and either worsening of functional class [FC] or need for additional PAH therapy), hospitalization for PAH worsening, PAH worsening (need for atrial septostomy or lung transplant; initiation of parenteral prostanoids or chronic O2 therapy), or all-cause death. Results: 1156 patients were randomized to placebo (n= 582) or selexipag (n= 574); 20% were PAH therapy naive, 47% were on monotherapy (ERA or PDE-5i) and 33% on combination therapy (ERA and PDE-5i) at baseline. The mean duration of selexipag and placebo treatment was 76.4±50.45 and 71.2±48.32 weeks, respectively. Selexipag reduced the risk of M/M events vs placebo (log-rank p 3% over placebo) were headache, diarrhea, nausea, jaw pain, myalgias, pain in extremity, flushing and arthralgia, consistent with prostacyclin effects. Conclusion: Selexipag demonstrated a significant effect on the time to first M/M event in PAH patients and had an acceptable safety profile. The treatment effect was observed irrespective of background treatment with ERA, PDE-5i, or both. Results from GRIPHON indicate selexipag is an efficacious PAH treatment. This study was funded by Actelion Pharmaceuticals. Medical writing support was provided by apothecom scopemedical ltd and was funded by Actelion Pharmaceuticals.