The Impact of ERA Switching on Risk Stratification in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare, progressive, and potentially life-threatening disease characterized by pulmonary vascular remodeling, increased pulmonary vascular resistance, and right ventricular dysfunction. The endothelin pathway plays a central role in its pathophysiology and is targeted by endothelin receptor antagonists (ERAs), including ambrisentan and bosentan. Ambrisentan is a selective ETA receptor antagonist, whereas bosentan blocks both ETA and ETB receptors. Although transitions between ERAs occur in clinical practice, evidence regarding the clinical impact of switching from ambrisentan to bosentan remains limited. ACTION is a retrospective, observational, single-center cohort study evaluating adult patients with pulmonary arterial hypertension (World Health Organization Group 1) and/or chronic thromboembolic pulmonary hypertension (World Health Organization Group 4) confirmed by right heart catheterization. Patients who switched from ambrisentan to bosentan because of a national ambrisentan shortage will be compared with clinically similar patients who remained on ambrisentan. Clinical, functional, and laboratory data recorded at baseline and at 3 to 6 months of follow-up will be assessed. The primary outcome is the proportion of patients with worsening risk stratification after switching from ambrisentan to bosentan compared with patients who continued ambrisentan. Risk will be evaluated using the COMPERA 2.0 and REVEAL Lite 2 assessment tools. Secondary outcomes include changes in World Health Organization/New York Heart Association functional class, 6-minute walk distance, BNP levels, individual risk-assessment components, hepatic enzymes, hemoglobin levels, and clinically relevant events such as hospitalization, emergency department visits, initiation of supplemental oxygen, and right heart failure decompensation.