Haemodynamic effects of riociguat in CTEPH and PAH: a 10-year observational study.

Background Long-term treatment with riociguat has been shown to enhance exercise capacity in patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). This study sought to evaluate the long-term haemodynamic effects of riociguat in patients with PAH and inoperable CTEPH. Methods During this single-centre long-term observational study, riociguat was administered at a three-times-daily dose of up to 2.5 mg. The primary outcome was pulmonary vascular resistance (PVR). The secondary outcomes included mean pulmonary arterial pressure (PAP), cardiac index, mortality, clinical worsening events, 6-min walk distance (6MWD) and World Health Organization functional class (WHO FC). Results 37 patients (CTEPH n=19; PAH n=18) were included. The median follow-up period was 96 months. The survival estimates for all the patients at 1/3/5/8 years were 0.97/0.86/0.72/0.61, without significant differences between patients with CTEPH and PAH. At the final data cut-off, PVR decreased (1232±462 dyn·s·cm-5versus 835±348 dyn·s·cm-5, p<0.001), cardiac index increased (1.7±0.4 L·min-1·m-2versus 2.4±0.5 L·min-1·m-2, p<0.001), 6MWD increased by 43.1±59.6 m, and WHO FC improved/stabilised/worsened in 40%/35%/25% of patients versus baseline. Improvement in PAP was not shown. Compared with patients in WHO FC I/II and III/IV at baseline, the 8-year clinical worsening-free survival estimates were 0.51 versus 0.19 (p=0.026). Conclusions Riociguat improved PVR and cardiac index for up to 8 years, but not PAP. WHO FC may have certain predictive value for the long-term prognosis.