Haemodynamic and Clinical Impacts of Switching Phosphodiesterase-5 Inhibitors to Riociguat in Patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH) after Balloon Pulmonary Angioplasty (BPA) – A Prospective Cohort Study

Abstract Background For patients with chronic thromboembolic pulmonary hypertension (CTEPH), balloon pulmonary angioplasty (BPA) has been associated with superior reductions in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) when compared to riociguat. In patients with pulmonary arterial hypertension (PAH), greater clinical improvements were observed after switching from phosphodiesterase-5 inhibitors (PDE5i) to riociguat. However, the impact of transitioning from PDE5i to riociguat on pulmonary haemodynamics and functional outcomes after BPA remains unclear. Methods This prospective, open-label, single-arm, study enrolled CTEPH patients who remained symptomatic following BPA. After a 24-hour PDE5i washout period, patients were switched to riociguat. At week 26, primary outcomes assessed changes in haemodynamics including mPAP and PVR. Secondary endpoints evaluated cardiac index; functional status including WHO functional class, 6-minute walking distance (6MWD), REVEAL Lite 2 score; biochemical markers such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP); and echocardiographic measurements of right-heart function. Treatment-related adverse events and clinical worsening were monitored throughout the study. Results From July 2024 to January 2025, 16 patients (mean age 62.3 ± 14.6 years; 75% female) were recruited, with 14 completing the 26-week follow-up. At week 26, significant reductions occurred in mPAP (-4.79 mmHg; Confidence Interval [CI] -8.05 to -1.52; p = 0.007) and PVR (-2.16 Wood units; CI -3.64 to -0.69; p = 0.007). Significant improvements were also noted in cardiac index, WHO functional class, 6MWD, REVEAL Lite 2 score and NT-proBNP levels. Echocardiographic measurements of right-heart function did not demonstrate significant improvement. Treatment-related adverse events were observed in 11 patients (68.75%). Clinical worsening occurred in four patients, including two deaths unrelated to treatment and two unplanned hospitalisations due to pulmonary hypertension. Conclusion In CTEPH patients after completion of BPA, replacing PDE5i with riociguat significantly enhanced pulmonary haemodynamics and functional capacity but was accompanied by a considerable risk of treatment-related adverse events. Trial registration: ClinicalTrials.gov Identifier NCT06715280 retrospectively registered on 26/11/2024.