Extended prospective follow-up of a randomised comparison of riociguat and selexipag under multimodal therapy in inoperable chronic thromboembolic pulmonary hypertension

Background Multimodal therapy combining balloon pulmonary angioplasty (BPA) and pulmonary vasodilators has become the standard therapeutic strategy for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). While riociguat is the only oral agent approved worldwide for inoperable CTEPH, selexipag is approved only in Japan. Comparative data between these two agents in the era of multimodal treatment are limited. Purpose We aimed to compare the therapeutic effects of riociguat and selexipag in patients with inoperable CTEPH at three time points: baseline, after up-titration of pulmonary vasodilators, and after the final BPA session. Methods This study was based on a prospective investigational randomised controlled trial. Twenty-four treatment-naïve patients with inoperable CTEPH were randomised to receive either riociguat or selexipag, with pulmonary vascular resistance (PVR) used as an allocation factor. The assigned drug was titrated to the maximum tolerated dose. The first follow-up assessment was performed at week 20. Subsequently, patients underwent BPA, and a final follow-up evaluation was conducted approximately six months after the final BPA session. Of the 24 enrolled patients, 9 in each group completed the final follow-up and were included in this analysis. Results Among the 18 patients analysed, the median age was 75 years (IQR 69–78), 78% were female. PVR decreased significantly and consistently from baseline to first follow-up and to final follow-up. In the riociguat group, median PVR significantly decreased from 7.1 WU (IQR 6.0–10.2) at baseline to 5.4 WU (IQR 3.3–5.9) at first follow-up and to 2.7 WU (IQR 2.4–3.0) at final follow-up (both Bonferroni-adjusted p=0.012). In the selexipag group, median PVR significantly decreased from 9.6 WU (IQR 7.5–12.6) to 6.9 WU (IQR 6.1–10.7) and to 3.4 WU (IQR 2.1–4.3) (Bonferroni-adjusted p=0.035 and p=0.012, respectively). The magnitude of PVR reduction from baseline to final follow-up did not differ significantly between groups (median −4.2 vs −7.7 WU, p=0.387). From baseline to post-BPA, mean pulmonary arterial pressure significantly decreased in both groups, and cardiac index significantly increased except in the riociguat group. As a sub-analysis, exercise right heart catheterisation was performed at all three time points in 7 patients in the riociguat group and 6 in the selexipag group. The mean pulmonary arterial pressure–cardiac output slope decreased from baseline to post-BPA in both groups (riociguat: 11.59 [IQR 6.91–16.68] to 4.4 [3.74–7.94]; selexipag: 9.87 [6.76–14.9] to 4.68 [4.02–5.88]; both p = 0.031). Conclusion Both riociguat and selexipag demonstrated significant hemodynamic improvements in treatment-naïve patients with inoperable CTEPH before and after BPA. Selexipag showed efficacy comparable to riociguat within a multimodal treatment strategy, supporting its role as an effective pulmonary vasodilator in this setting.