RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors

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 <3.0 L.min(-1).m(-2) and pulmonary vascular resistance >400 dyn.s.cm(-5) underwent a 1-3 day PDE5i treatment-free period before receiving riociguat adjusted up to 2.5 mg maximum t.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+/-sd 6MWD had increased by 31+/-63 m, NT-proBNP decreased by 347+/-1235 pg.mL(-1) and 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, M. M.
• Simonneau, G.
• Corris, P. A.
• Ghofrani, H. A.
• Klinger, J. R.
• Langleben, D.
• Naeije, R.
• Jansa, P.
• Rosenkranz, S.
• Scelsi, L.
• Grunig, E.
• Vizza, C. D.
• Chang, M.
• Colorado, P.
• Meier, C.
• Busse, D.
• Benza, R. L.