Change in ph therapy from PDE5I to riociguat is associated with significant incremental increase in cardiac index, decrease in pulmonary vascular resistance and mean arterial pressure

Purpose: Pulmonary hypertension (PH) is characterized by vascular remodeling and progressive constriction. Phosphodiesterase-5 inhibitors (PDE5i) are a well studied class of pulmonary vasodilators. Recently, a soluble guanylate cyclase stimulator, riociguat, has also been used in place of PDE5i but the benefit of switching from PDE5 to this drug has not been established. We sought to investigate the clinical and hemodynamic effects of replacing PDE5i with riociguat. Methods: We retrospectively analyzed data from patients who had been switched from a PDE5i to riociguat for a clinical indication. Baseline (pre- PDE5i), on PDE-5i, and post-riociguat exchange hemodynamic and clinical data were analyzed to determine if any changes were associated with riociguat exchange. Covariate analysis was performed to correct for length of time on therapy and whether other PH specific therapies had been added or intensified. Results: 18 consecutive PDE5i to riociguat switch patients were screened for inclusion and, since 5 were found to have incomplete records, 13 were included for analysis. In comparing pre-PDE5i to post-PDE5i parameters, there were no significant hemodynamic or clinical differences between the groups after a mean of 172 weeks of follow-up despite 75% of patients having other PH therapies added or intensified. However, after PDE5i to riociguat exchange for a minimum of 12 weeks (mean 34 weeks), cardiac index (CI) by Fick increased by 0.41±0.16 L/min/m2 (p= 0.026), pulmonary vascular resistance (PVR) decreased by 1.56±0.67 WU (p= 0.037) and mean arterial pressure (MAP) decreased by 19±5 mmHg (p= 0.001). Further, covariate analysis showed no significant contribution from length of time on riociguat or whether PH therapies were intensified at the time of riociguat exchange. Conclusion: We conclude that PDE5i to riociguat exchange is a viable option for patients with worsening clinical status and, after 12 weeks, is associated with significantly increased CI, decreased PVR, and decreased MAP irrespective of intensifying other PH directed therapies or extended use of the drug beyond 12 weeks. Forthcoming data from the prospective RESPITE trial may aid in further delineating this relationship.