Comparative clinical evaluation of endothelin receptor antagonists in pulmonary arterial hypertension using a...

Endothelin receptor antagonists are important therapies for pulmonary arterial hypertension, but differences in efficacy, safety, monitoring requirements, drug interactions, costs, and accessibility complicate treatment selection.

To compare endothelin receptor antagonists across safety, efficacy, economic value, suitability, accessibility, and innovation, and to develop a multidimensional framework for clinical pharmacy decision-making and formulary management.

A structured framework was developed through a two-round Delphi process involving 19 multidisciplinary experts. Indicators were classified as quantitative or qualitative and organized into six domains. Consensus was assessed using the authority coefficient, coefficient of variation, and Kendall's coefficient of concordance. Weights were determined using the analytic hierarchy process and integrated through multi-criteria decision analysis. Quantitative evidence was derived from regulatory sources, randomized trial meta-analysis, national pricing databases, and hospital procurement records. Qualitative indicators, including monitoring requirements, drug interactions, adherence-related factors, accessibility, and innovation, were scored using predefined criteria. Economic value was evaluated in the Chinese healthcare context using annual drug acquisition costs, affordability ratios, and cost per metre improvement in 6-min walk distance.

The Delphi process established a framework comprising six domains, 13 subdomains, and 32 indicators, with good reliability and consistency: authority coefficient 0.82, Cronbach's alpha 0.864, and Kendall's W 0.412. Twelve randomized controlled trials were included in the quantitative synthesis. All endothelin receptor antagonists improved exercise capacity and hemodynamic outcomes, although the magnitude varied. Ambrisentan showed comparatively larger improvements in 6-min walk distance and a trend toward lower odds of adverse drug reactions. Annual drug acquisition costs were ¥24,600 for ambrisentan, ¥17,820 for bosentan, and ¥57,240 for macitentan. The corresponding costs per metre improvement were ¥140.12/m, ¥142.38/m, and ¥1470.71/m, and annual cost-to-income ratios were 87.15%, 63.13%, and 202.78%, respectively. After weighted integration, ambrisentan achieved the highest overall score, followed by bosentan and macitentan.

Within the proposed MCDA framework, ambrisentan achieved the highest overall score across multiple clinical and practical dimensions. The framework provides a transparent tool for structured evaluation, although economic and accessibility findings should be interpreted within the Chinese healthcare context.