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