TY - JOUR T1 - Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/09031936.00182909 SP - erj01829-2009 AU - H.A. Ghofrani AU - M.M. Hoeper AU - M. Halank AU - F.J. Meyer AU - G. Staehler AU - J. Behr AU - R. Ewert AU - G. Weimann AU - F. Grimminger Y1 - 2010/01/01 UR - http://erj.ersjournals.com/content/early/2010/06/07/09031936.00182909.abstract N2 - We assessed the therapeutic potential of riociguat, a novel soluble guanylate cyclase stimulator, in adults with chronic thromboembolic pulmonary hypertension (CTEPH, n=42) or pulmonary arterial hypertension (PAH, n=33) in WHO functional class II/III.In this 12-week, multicentre, open-label, uncontrolled phase II study, patients received oral riociguat 1.0–2.5 mg t.i.d. titrated according to systemic systolic blood pressure (SBP) (ClinicalTrials.gov identifier: NCT00454558) . Primary endpoints were safety and tolerability; pharmacodynamic changes were secondary endpoints.Riociguat was generally well tolerated. Asymptomatic hypotension (SBP<90 mmHg) occurred in 11 patients, but blood pressure normalised without dose alteration in nine and after dose reduction in two. Median 6-minute walking distance increased in patients with CTEPH (+55.0 m from baseline [390 m]; p<0.0001) and PAH (+57.0 m from baseline [337 m]; p<0.0001); patients in functional class II or III and bosentan-pre-treated patients showed similar improvements. Pulmonary vascular resistance was significantly reduced by 215 dyn.sec·cm−5 from baseline (709 dyn.sec·cm−5; p≤0.0001).Forty-two patients (56%) were considered to have experienced drug-related adverse events (AEs; 96% mild or moderate). Dyspepsia, headache and hypotension were the most frequent AEs. Study discontinuation because of AEs was 4%.These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity, symptoms, and pulmonary haemodynamics in CTEPH and PAH. RCTs are underway. ER -