ARIES-3: Ambrisentan Therapy in a Diverse Population of Patients with Pulmonary Hypertension

Introduction: Ambrisentan is an oral, once daily, endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension (PAH). Previous studies of ambrisentan were limited to patients with Group 1 PAH and often excluded patients receiving other pulmonary hypertension (PH) therapies. Aims: ARIES-3 was an open-label study evaluating efficacy and safety of ambrisentan in patients with various PH etiologies and background PH medications. Patients received 5 mg ambrisentan once daily for 24 weeks. The primary endpoint was change from baseline in 6-minute walk distance (6MWD) at week 24. Results: A total of 224 patients with PH due to idiopathic and familial PAH (31%), connective tissue disease (18%), chronic hypoxemia (22%), chronic thromboembolic disease (13%), or other etiologies (16%) were enrolled and 53% of patients received stable background PAH therapies. After 24 weeks of therapy, an increase in 6MWD (+21 m; 95% CI: 12-29) and a decrease in B-type natriuretic peptide (-26%; 95% CI: -34 to -16%) was observed in the overall population compared to baseline; however, increases in 6MWD were not observed in several non-Group 1 PH subpopulations. Peripheral edema, headache, and dyspnea were the most common adverse events. Conclusion: This study reconfirms the results of previous placebo-controlled studies, which demonstrate that ambrisentan is well tolerated and provides benefit in patients with PAH. Definitive conclusions regarding the safety and efficacy of ambrisentan in specific non-Group 1 PH etiologies cannot be determined and larger, controlled studies will be necessary to determine the efficacy and safety of ambrisentan in these populations.