Comparable exercise hemodynamic improvements with riociguat and selexipag under multimodal therapy including balloon pulmonary angioplasty in inoperable chronic thromboembolic pulmonary hypertension

Background In current clinical practice, multimodal treatment combining balloon pulmonary angioplasty (BPA) and pulmonary vasodilators represents the standard approach for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Riociguat is approved worldwide for inoperable CTEPH, whereas selexipag is approved only in Japan. However, direct comparative data between these agents are limited, particularly regarding exercise hemodynamics assessed by exercise right heart catheterization (RHC). Objective We aimed to compare the efficacy of riociguat and selexipag in patients with inoperable CTEPH receiving multimodal therapy including BPA. Methods This was a single-center retrospective observational study. We analyzed patients who underwent BPA at our institution between August 2021 and February 2026. All patients received either riociguat or selexipag prior to BPA. Baseline data were collected before initiation of pulmonary vasodilator therapy. Follow-up evaluation was performed approximately 6 months after the final BPA session while patients continued pulmonary vasodilator therapy. The primary outcomes were changes in pulmonary vascular resistance (PVR) at rest and the mean pulmonary arterial pressure–cardiac output (mPAP/CO) slope obtained during exercise RHC. Secondary outcomes included changes in other hemodynamic parameters and exercise-induced changes in cardiac index (ΔCI). Results A total of 48 patients were included (riociguat group; n=32, selexipag group; n=16). There was no significant difference in baseline PVR between the groups (8.3 ± 4.2 WU vs. 10.9 ± 4.6 WU, p = 0.054). At 6-month follow-up after the final BPA session, the mean daily dose was 5.8 ± 2.1 mg/day for riociguat and 2.3 ± 0.7 mg/day for selexipag. PVR was significantly reduced from baseline in both groups, and there was no significant difference between riociguat and selexipag at follow-up (2.9 ± 1.0 vs 3.6 ± 1.2 WU; p = 0.089; Figure. 1). In addition, the mPAP/CO slope during exercise was significantly reduced in the selexipag group (17.3 ± 16.3 to 4.9 ± 1.0, p = 0.003), and there was no significant difference in the change of mPAP/CO slope between the groups (riosiguat; -6.6 ± 11.9, selexipag; -12.4 ± 16.4, p = 0.403; Figure. 2). Under multimodal therapy including BPA, selexipag also demonstrated significant reductions in mPAP and increases in CI (p = 0.002 and p = 0.005, respectively), comparable to those observed with riociguat. Maximal workload during exercise increased significantly in both groups, and ΔCI during exercise was comparable between groups (p = 0.142, Figure. 3). Conclusions In patients with inoperable CTEPH undergoing multimodal treatment including BPA, both riociguat and selexipag significantly improved resting and exercise hemodynamics. Selexipag demonstrated efficacy comparable to riociguat, suggesting that effective hemodynamic improvement can also be achieved with selexipag in this clinical setting.