OBJECTIVES: Indications for PAH medications vary between countries, and products may have restricted reimbursement based on policies limiting treatment to WHO functional class (FC) III patients. In the PATENT-1 study, the novel soluble guanylate cyclase stimulator riociguat significantly improved 6-minute walking distance (6MWD) and a range of secondary endpoints in patients with PAH. This subgroup analysis of PATENT-1 investigated the proportion of FC III/IV patients achieving threshold criteria. METHODS: PATENT-1 was a double-blind, randomized Phase III study in which patients with PAH received 12 weeks’ oral treatment with placebo, an individual titration of riociguat (up to 2.5 mg tid), or a capped titration of riociguat (up to 1.5 mg tid). Increase in 6MWD ≥40 m, 6MWD ≥380 m, cardiac index (CI) ≥2.5 L/min/m2, pulmonary vascular resistance (PVR) <500 dyn·s·cm−5, mixed venous oxygen saturation (SvO2) ≥65%, FC I/II, absence of clinical worsening events, and NT-proBNP <1800 pg/mL were chosen as positive response criteria based on studies showing their prognostic relevance at baseline and after targeted therapy. RESULTS: At baseline, 241 patients were in FC III/IV (FC IV n=4) across the three treatment groups, and similar proportions met selected criteria in the riociguat individual titration (n=141) and placebo groups (n=61). At Week 12/last visit, the proportion of patients fulfilling these criteria was higher in the riociguat individual titration group than the placebo group for all parameters: increase in 6MWD ≥40m (44% vs 15%), 6MWD ≥380m (49% vs 36%), CI ≥2.5 L/min/m2 (75% vs 43%), PVR <500 dyn·s·cm−5 (52% vs 27%), SvO2 ≥65% (68% vs 35%), FC I/II (33% vs 23%), absence of clinical worsening events (99% vs 90%), and NT-proBNP <1800 pg/mL (84% vs 64%). CONCLUSIONS: In this population of predominantly FC III PAH patients, riociguat increased the proportion fulfilling criteria defining a positive response to therapy.