Abstract Background Multimodal treatment is now the standard therapeutic strategy for patients with chronic thromboembolic pulmonary hypertension (CTEPH), and pharmacological therapy is one of the components which plays an important role. Although riociguat is the only drug approved for CTEPH patients worldwide, selexipag is approved in Japan for CTEPH patients. Therefore, the safety and efficacy analysis of selexipag compared with riociguat is lacking. Purpose We aimed to evaluate the difference of the efficacy and safety of riociguat and selexipag in patients with inoperable CTEPH. Methods This study was a prospective investigational randomized controlled trial. In total, 24 patients were enrolled and randomized to either riociguat or selexipag treatment group with pulmonary vascular resistance (PVR) as an allocation factor. Either of the allocated drug was titrated to maximum tolerated dose within 16 weeks. At 20 weeks, follow-up examination was performed. Among 24 patients, one patient in riociguat group and 2 patients in selexipag group withdrew during the study period. As a result, 11 patients in riociguat group and 10 patients in selexipag group completed the follow-up and were analyzed. Results In total 21 patients who completed the follow-up, all were treatment naive, median age was 75 (IQR 69–80) years, 24% were male, and median baseline PVR was 8.9 (IQR 6.0–12.2) WU. The baseline characteristics were comparable in both groups including PVR. PVR significantly decreased from baseline to follow-up in both riociguat group (median 7.09WU IQR 6.03–10.25 to median 5.39WU IQR 3.23–6.24, P=0.002) and selexipag group (median 10.35WU IQR 7.45–15.8 to median 7.85WU IQR 6.05–11.3, P=0.006). There was no significant difference of change in PVR with riociguat and selexipag group (median -2.85 vs -2.605 WU, respectively, P=0.916). In riociguat group, mean pulmonary artery pressure significantly decreased from baseline to follow-up (median 33.0 mmHg IQR 30.5–38.0 to median 27.0 mmHg IQR 22.5–31.5, respectively, P=0.025), while mean arterial blood pressure also significantly decreased (median 102.0 mmHg IQR 90.5–104.5 to median 81.0 mmHg IQR 78.5–87.5, respectively, P=0.025). In selexipag group, cardiac index significantly improved (median 1.96 L/min/m2 IQR 1.59–2.30 to median 2.30 L/min/m2 IQR 2.20–2.44, respectively, P=0.037), while SaO2 significantly decreased from baseline to follow-up (median 89.6% IQR 86.8–92.2 to median 87.5% IQR 85.3–90.1, respectively, P=0.02). Exercise tolerance and BNP was comparable at baseline and after treatment in both groups. Conclusion Riociguat and selexipag was significantly effective in treatment naive patients with inoperable CTEPH. Selecting the drug based on the characteristics of each drug could contribute to more favorable result in patients with CTEPH.
Nakano et al. (Sat,) studied this question.