Even though
pulmonary arterial hypertension (PAH) remains an incurable disease, the combination of PAH-specific
therapies allowed evolving from symptom-based strategies to others aiming to move patients to low-risk conditions.
Endothelin-1 (ET-1) receptor antagonists emerged as specific-PAH drugs that can be used in combination with other specific
therapies. This work aimed to perform a prospective clinical assessment of patients with PAH that switched from
bosentan to
macitentan (POTENT), due to inadequate response. POTENT is a prospective, open-label, single-arm, uncontrolled study including PAH patients from our ongoing SAUDIPH registry. It enrolled 50 PAH patients divided as follows: idiopathic/
heritable pulmonary arterial hypertension (I/
HPAH); n = 24; PAH associated with
congenital heart disease, n = 19; PAH associated with
connective tissue diseases, n = 5; and
pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH), n = 2. At baseline, most patients were in World Health Organization Functional Class (WHO FC) II/III (52.0%). After switching to
macitentan, patients were more likely to be in WHO FC I/II (78%) and 22% of the overall cohort moved to a lower risk condition, with three low risk stratification parameters. Mean 6-min walking distance increased about 34 m after 12 months, with a significant mean change over time (12.63 ± 11.69 at month 3 vs. 40.75 ± 12.57 at month 12, p = 0.002). Most haemodynamic parameters decreased over time, with corresponding negative mean changes (p < 0.001). The safety of
macitentan was confirmed by the absence of anaemia and liver injury; clinical worsening was observed only in a small group of patients. In general,
macitentan might be a valid alternative to
bosentan in PAH stable patients on combination
therapy with insufficient clinical response, and presenting intermediate and high-risk parameters. We anticipate that studying this strategy in PAH subgroups would further clarify its potential and limitations.