Long-term efficacies of selective vasodilators in pulmonary arterial hypertension: A comprehensive comparison using a spontaneous reporting database

Aims : There is no clinical evidence of differences in drugs associated with long-term survival in patients with pulmonary arterial hypertension (PAH) due to a small population and the lack of information on death in the Japanese medical database systems. This study evaluated whether patient data from a spontaneous reporting database could be used for comparing the effects of pulmonary vasodilators on long-term survival in PAH patients. Methods : PAH patient data reported in the Japanese Adverse Drug Event Report (JADER) database from April 2004 to July 2022 were extracted. Kaplan-Meier curves were used to compare survival times. Adjusted hazard ratios (aHRs) for all-cause mortality were determined using Cox proportional hazards models. Results : Of 1969 PAH patients reported in the JADER database, 1208 patients were included in the survival analyses. The patient demographics were similar to those of the PAH population reported in the Japan Pulmonary Hypertension Registry. Among drugs targeting the prostacyclin pathway, epoprostenol was most associated with long-term survival (aHR: 0.38; 95% confidence interval [CI], 0.23–0.64). The PAH patients treated with endothelin receptor antagonists had improved survival, especially in the macitentan users (aHR: 0.30; 95% CI, 0.22–0.42). Sildenafil was associated with a poor prognosis in the PAH patients (aHR: 1.56; 95% CI, 1.19–2.04). Conclusion : Although our results must be interpreted with caution due to several limitations inherent to spontaneous reporting databases, our approach using the JADER database for survival analysis may provide useful information in limited situations such as the treatment of rare diseases including PAH.