Switching from PDE5 inhibitors to riociguat in PAH patients with inadequate response increased 6-minute walking distance by a mean of 31 m and improved WHO functional class in 54% at 24 weeks.
Does switching from PDE5i to riociguat improve functional capacity and biomarkers in PAH patients with inadequate response to PDE5i?
Switching from PDE5i to riociguat appears feasible and may improve exercise capacity and biomarkers in selected PAH patients with inadequate response to PDE5i.
A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients. RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO) functional class (FC) III, with 6-min walking distance (6MWD) 165–440 m, cardiac index 400 dyn·s·cm−5underwent a 1–3 day PDE5i treatment-free period before receiving riociguat adjusted up to 2.5 mg maximumt.i.d. Exploratory end-points included change in 6MWD, WHO FC,N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and safety. Of 61 patients enrolled, 51 (84%) completed RESPITE. 50 (82%) were receiving concomitant endothelin receptor antagonists. At week 24, mean±sd6MWD had increased by 31±63 m, NT-proBNP decreased by 347±1235 pg·mL−1and WHO FC improved in 28 patients (54%). 32 patients (52%) experienced study drug-related adverse events and 10 (16%) experienced serious adverse events (2 (3%) study drug-related, none during the PDE5i treatment-free period). Six patients (10%) experienced clinical worsening, including death in two (not study drug-related). In conclusion, selected patients with PAH may benefit from switching from PDE5i to riociguat, but this strategy needs to be further studied.
Hoeper et al. (2017) studied pulmonary arterial hypertension (PAH) (n=61). Riociguat was evaluated on change in 6-min walking distance (6MWD). Switching from PDE5 inhibitors to riociguat in PAH patients with inadequate response increased 6-minute walking distance by a mean of 31 m and improved WHO functional class in 54% at 24 weeks.