Tadalafil plus endothelin receptor antagonists in connective tissue disease-associated pulmonary arterial hypertension: A multicenter study on exercise capacity and cardiac outcomes.

Abstract

Background and objectives: Pulmonary arterial hypertension (PAH) is a life-threatening condition that requires optimized medical therapy to maintain a low-risk profile. This study assessed the effects of initial PAH-specific combination therapy with tadalafil/sildenafil on clinical and functional outcomes in a real-world setting.

Methods: We conducted a multicenter retrospective study of 85 patients diagnosed with connective tissue disease-associated PAH (CTD-PAH) via right heart catheterization from 2009 to 2023. Data on treatment regimens and efficacy measures, including 6-min walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenicity 2 (sST2), World Health Organization (WHO) functional class, risk stratification, treat-to-target status and survival, were collected.

Results: Patients receiving initial combination therapy with endothelin receptor antagonists (ERAs) and phosphodiesterase-5 inhibitors showed varied improvements. The tadalafil plus ERAs combination significantly reduced NT-pro BNP levels and improved risk status (P < 0.05). Notable enhancements in 6MWD, soluble ST2, and WHO functional class were observed in the tadalafil plus ERA group (P < 0.001), but not in the sildenafil group (P > 0.05). Additionally, 1-year treat-to-target rates were higher in the tadalafil plus ERA group (73.5%) than in the sildenafil group (45.6%, P = 0.005).

Conclusion: These findings suggest that tadalafil combined with ERAs leads to better improvements in exercise capacity, functional class, and treatment goals compared to sildenafil-based regimens, offering valuable insights for optimizing CTD-PAH treatment.