Abstract

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.