Pulmonary arterial hypertension (PAH) is a rare, progressive, and potentially fatal disease characterized by increased pulmonary vascular resistance and right ventricular dysfunction. Among the four major molecular pathways involved in PAH pathophysiology-nitric oxide, prostacyclin, activin, and endothelin-1 (ET-1)-the endothelin pathway plays a central role. Endothelin-1 acts on ETA and ETB receptors, inducing vasoconstriction and vascular remodeling.
Endothelin receptor antagonists (ERAs) are cornerstone therapies in PAH. Ambrisentan is selective for ETA and associated with a lower risk of hepatotoxicity. Bosentan, a dual ERA (ETA/ETB), has well-established efficacy but a higher incidence of liver enzyme elevation, with approximately 9% of patients experiencing hepatic side effects and about 2% discontinuing therapy due to hepatotoxicity.
While transitions between ERAs occur in routine clinical practice, data on their clinical impact are scarce. This prospective, observational, single-center cohort study aims to evaluate the effect of switching from ambrisentan to bosentan on risk stratification using the COMPERA 2.0 and REVEAL Lite 2.0 scores at 3-6 months post-switch.
Secondary outcomes include variations in functional class (WHO/NYHA), 6-minute walk distance (6MWD), NT-proBNP levels, incidence of adverse events (with a focus on hepatotoxicity), and hematologic parameters such as anemia.
The study will enroll adult patients (≥18 years) with confirmed PAH by right heart catheterization who have undergone a documented switch from ambrisentan 10 mg to bosentan 125 mg within the last 6 months. The primary endpoint is the proportion of patients whose risk category changes post-transition according to COMPERA 2.0 and REVEAL Lite 2.0. The results are expected to provide clinically relevant insights into therapeutic decisions involving ERA transitions in PAH management.
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
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. The cohort is representative of a real-world PAH population receiving care at a specialized pulmonary hypertension center. Patients will be prospectively followed for clinical, functional, and laboratory outcomes under routine care conditions.
Cohort
Prospective
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.
Change in risk category according to used scores
Proportion of patients who change their clinical risk category (improvement, worsening, or no change) based on scores between baseline (at the time of medication switch) and follow-up (3 to 6 months after the switch from ambrisentan to bosentan).
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.
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.
Change in NT-proBNP Levels
Variation in serum NT-proBNP levels between baseline and follow-up to assess cardiac stress and right ventricular function.
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.
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