Abstract Background: Combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 inhibitor (PDE-5i) is widely used for pulmonary arterial hypertension (PAH). While ERA/Sildenafil combinations were once common, suggestions exist that sildenafil bioavailability is reduced by ERA co-administration. This systematic review aimed to compare the effectiveness of ERA/Sildenafil versus ERA/Tadalafil in treating PAH by analyzing invasive hemodynamic data. Methodology: A comprehensive literature search was conducted using keywords (ERA, Sildenafil, Tadalafil, PAH) in PubMed, Embase, Clarivate Analytics/Web of Science Core Collection, and Wiley/Cochrane Library. The search included clinical trials and observational studies published up to July 2024, comparing ERA/Sildenafil and ERA/Tadalafil regimens reporting invasive hemodynamic measurements (mean pulmonary artery pressure mPAP and pulmonary vascular resistance PVR). A meta-analysis was performed using Julius Artificial intelligence software (applying Python tools in data analysis) to assess statistical significance in PVR and mPAP between the two groups. Results: Two retrospective studies were included, comprising 160 patients in the ERA/Sildenafil regimen and 62 in the ERA/Tadalafil regimen. The mPAP was significantly lower in the ERA/Tadalafil group ( P < 0.001), while a lower PVR was observed in the same group, though achieving less statistical significance ( P = 0.04). Conclusion: This systematic review suggests that Tadalafil may be better suited for dual therapy with ERA compared to Sildenafil, given the statistically significant improvement in mPAP. However, this conclusion is based on limited evidence from retrospective studies. Therefore, more clinical trials, particularly randomized controlled trials, are needed to confirm these findings and guide clinical practice. This systematic has been registered in PROSPERO Registration ID: 1048829.
AbdelMassih et al. (Thu,) studied this question.