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.
Age ≥ 18 years
Confirmed diagnosis of pulmonary arterial hypertension (PAH) by right heart catheterization
Documented therapeutic switch from ambrisentan (10 mg once daily) to bosentan (125 mg twice daily) within the previous 6 months for the switch group
Treatment with ambrisentan for at least 6 months without switching to bosentan for the maintenance group
History of severe hepatic impairment
Incomplete clinical or laboratory records that prevent risk score calculation
Inability to attend clinical follow-up between 3 and 6 months after medication switch
This study will include adult patients (≥18 years old) diagnosed with pulmonary arterial hypertension (PAH), confirmed by right heart catheterization, who have undergone a clinically indicated therapeutic switch from ambrisentan to bosentan within the past 6 months or who remained on ambrisentan for at least 6 months without switching. The cohort is representative of a real-world PAH population receiving care at a specialized pulmonary hypertension center. Patients will be retrospectively evaluated for clinical, functional, and laboratory outcomes under routine care conditions.
Cohort
Retrospective
Switch from Ambrisentan to Bosentan
Other interventionThis intervention refers to a therapeutic switch from ambrisentan (10 mg once daily) to bosentan (125 mg twice daily) in adult patients with pulmonary arterial hypertension (PAH), performed as part of routine clinical care. The switch was not assigned by the investigators but was made based on clinical indications prior to study enrollment. Patients are followed prospectively for up to 6 months to assess changes in risk stratification, functional status, laboratory parameters, and safety outcomes.
Maintenance of Ambrisentan Therapy
DrugContinued treatment with ambrisentan 10 mg once daily without transition to bosentan, as part of routine clinical care. Treatment was not assigned by the investigators. Clinical, functional, laboratory, and safety outcomes are assessed over a 3- to 6-month period.
Change in risk category according to used scores
Proportion of participants with worsening clinical risk category from baseline to follow-up, comparing patients who switched from ambrisentan to bosentan with patients who remained on ambrisentan..
Change in Functional Class
Change in functional class between baseline and follow-up (classified as improvement, worsening, or no change), as an indicator of clinical status and exercise tolerance, and compared between the study groups.
Change in 6-Minute Walk Distance (6MWD)
Change in the distance walked during the 6-minute walk test (6MWD) between baseline and follow-up, measured in meters, to assess exercise capacity, and compare bewtween groups
Change in NT-proBNP Levels
Variation in serum NT-proBNP levels between baseline and follow-up to assess cardiac stress and right ventricular function. And comparison of this change between the study groups.
Incidence of Hepatotoxicity
Number and proportion of patients who develop elevation of AST or ALT above 3 times the upper limit of normal during the follow-up period, indicating possible liver toxicity. And compared between the study groups.
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