Abstract Rationale Endothelin receptor antagonists (ERAs) are key therapies for pulmonary arterial hypertension (PAH). Real-world data on ERA switching are limited. In 2025, a nationwide shortage of ambrisentan in Brazil required substitution with bosentan. We evaluated short-term clinical and risk changes after this transition. Methods This retrospective single-center cohort included 72 adults with Group 1 PAH who switched from ambrisentan to bosentan. Demographic, functional, and laboratory data were collected at baseline and 3-6 months post-switch. Risk stratification used COMPERA 2.0 and REVEAL Lite 2. Paired comparisons used Wilcoxon and McNemar-Bowker tests. Results Mean age was 49.8 ± 14.6 years; 83.3% were female. Time since diagnosis averaged 5.0 ± 4.2 years, and ambrisentan exposure 39.2 ± 30.5 months. Major etiologies were idiopathic (52.8%) and connective-tissue disease (15.3%). Combined therapy was double in 51.4% and triple in 48.6%. After switching, 6-minute walk distance declined significantly (419.5 → 386.5 m; p = 0.010), whereas BNP increased modestly (median 99 → 135 pg/mL; p = 0.097). WHO functional class showed no overall statistical change (p = 0.91) though a slight shift toward higher classes occurred, with 10 patients (14%) worsening. According to COMPERA 2.0 (n = 72), risk distribution changed from 41.7% low / 30.6% intermediate-low / 20.8% intermediate-high / 0% high to 25.0% / 29.2% / 23.6% / 4.2% (p = 0.0018). By REVEAL Lite 2, categories shifted from 55.6% low / 29.2% intermediate / 13.9% high to 38.9% / 29.2% / 25.0% (p 0.0001), indicating upward risk reclassification. Clinical decompensation, defined as early worsening with deterioration in class, dyspnea, or syncope, occurred in 23 patients (31.9%). Those who decompensated had higher baseline right atrial pressure (12.3 ± 4.6 vs. 9.6 ± 4.8 mmHg; p = 0.011) but no significant differences in cardiac index, pulmonary vascular resistance, or mixed venous oxygen saturation. One patient (1.4%) presented with hepatotoxicity, recovering fully after bosentan discontinuation. Conclusions In this real-world cohort, short-term switching from ambrisentan to bosentan was associated with a significant functional decline and worsening in risk assessment. Hepatotoxicity was rare. Patients with higher baseline right atrial pressure were more likely to decompensate. These findings suggest a different efficacy profile between the two ERAs that should be taken into account when switching, reinforcing the need for close monitoring due to the risk of deterioration. This abstract is funded by: None
Nascimento et al. (Fri,) studied this question.