Comprehensive Clinical Evaluation of Endothelin Receptor Antagonists in Pulmonary Arterial Hypertension Using Multi-Criteria Decision Analysis

Introduction Endothelin receptor antagonists (ERAs), including ambrisentan, bosentan, and macitentan, are central to the treatment of pulmonary arterial hypertension (PAH). As patient survival improves, long-term management increasingly requires systematic evaluation of these agents to balance their efficacy, safety, cost, and accessibility. However, standardized frameworks that integrate the multiple dimensions of clinical value remain limited. Aim This study aimed to establish and apply a six-dimensional Multi-Criteria Decision Analysis (MCDA) framework to comprehensively assess the clinical value of ambrisentan, bosentan, and macitentan in the treatment of PAH. Method A structured evaluation system was developed using Delphi expert consultation and evidence synthesis from systematic reviews, meta-analyses of randomized controlled trials (RCTs), pharmacoeconomic assessments, and regulatory documents. Six core dimensions were included: safety, efficacy, economic value, suitability, accessibility, and innovation. Quantitative and qualitative indicators were normalized and weighted using the Analytic Hierarchy Process and integrated using the MCDA model. Sensitivity analyses were performed to verify the robustness of rankings. Results The final framework comprised six primary dimensions, 13 secondary indicators, and 32 tertiary indicators. Twelve RCTs met the inclusion criteria for quantitative analysis. All three ERAs improved exercise capacity and hemodynamic parameters, whereas ambrisentan exhibited superior tolerability. Economic evaluation showed that ambrisentan and bosentan offered better cost-effectiveness, with incremental cost-effectiveness ratios of ࿥140.12 per meter and ࿥142.38 per meter, respectively, compared with ࿥1,470.71 per meter for macitentan. Suitability analysis favored ambrisentan and macitentan because of their once-daily dosing and favorable adherence profiles. Bosentan demonstrated advantages in affordability owing to its lower cost and National Reimbursement Drug List coverage. Innovation assessment ranked macitentans as the highest for technological advancement. Integrated MCDA scoring indicated that ambrisentan achieved the greatest overall clinical value. Conclusion This study developed a multidimensional, evidence-based evaluation model for PAH therapy using MCDA. Ambrisentan achieved the highest comprehensive score across the six key dimensions, reflecting its balanced efficacy, safety, and economic performance. The proposed framework provides a practical tool for clinicians, pharmacists, and policymakers to support rational drug use, formulary management, and value-based decision making in PAH and other rare diseases.