CHEST-2 showed riociguat to be the first therapy to have sustained clinical effect in patients with CTEPH. We compared inoperable CTEPH and persistent/recurrent PH subgroup data from the final CHEST-2 datacut.
Patients with inoperable CTEPH or persistent/recurrent PH after PEA who completed the 16-week CHEST-1 study without ongoing riociguat-related SAEs were eligible to enter CHEST-2. All patients received riociguat up to 2.5 mg tid. Primary endpoints were safety and tolerability; secondary endpoints included 6MWD and WHO FC.
In total, 237 patients entered CHEST-2; 172 (73%) had inoperable CTEPH and 65 (27%) had persistent/recurrent PH. At the data cutoff (March 2014), 172 patients (73%) were ongoing. Median treatment duration was 116 weeks and 90% of patients remained on riociguat monotherapy. Improvements in 6MWD in the inoperable subgroup were more pronounced than in the persistent/recurrent subgroup, while improvements in WHO FC were similar (Table 1). Improvements in NT-proBNP, EQ-5D, and Borg dyspnea scores were also observed in both subgroups (Table 1). There were similar rates of AEs (99% vs 97%), and clinical worsening (22% vs 23%) in the inoperable vs persistent/recurrent PH subgroups, respectively. There were fewer SAEs in the inoperable vs persistent/recurrent PH subgroup (52% vs 62%), and higher survival (94% vs 89%).
Riociguat provided long-term clinical benefit in both inoperable CTEPH and persistent/recurrent PH after PEA, with good tolerability at 2 years. The improvements in 6MWD and WHO FC observed with riociguat treatment in CHEST-1 were sustained at 2 years in CHEST-2 in both subgroups.