Riociguat for pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD): A subgroup analysis from the PATENT studies

Abstract

Introduction: Riociguat treatment has shown beneficial effects in patients with pulmonary arterial hypertension (PAH) in a randomized, placebo‐controlled Phase III trial (PATENT‐1) and its open‐label long‐term extension (PATENT‐2). Here we investigated the safety and efficacy of riociguat in the subgroup of patients with persistent or recurrent PAH following complete surgical repair of congenital heart disease (CHD) in PATENT‐1 and PATENT‐2. Methods: In PATENT‐1, treatment‐naïve or pretreated patients with PAH received either placebo, riociguat up to 2.5 mg threetimes daily (tid) (2.5 mg‐maximum group), or riociguat up to 1.5 mg tid (1.5 mg‐maximum group; exploratory) for 12 weeks. Patients completing PATENT‐1 without ongoing drug‐related serious adverse events (SAEs) were eligible to enter PATENT‐2, in which all patients received open‐label treatment with riociguat. Results: There were 35 patients with persistent or recurrent PAH after complete surgical repair of CHD in PATENT‐1, of whom 33 (94%) entered PATENT‐2. At PATENT‐1 baseline, 57% of patients with PAH‐CHD were treatment‐naïve, most had atrial or ventricular septal defects (40% and 34%, respectively), all were in WHO FC II or III (60% and 40%, respectively), and mean time since last corrective surgery was 16.8 years. At Week 12 of PATENT‐1, patients in the riociguat 2.5 mg‐maximum group showed greater improvements from baseline in 6MWD (primary endpoint) and a range of secondary efficacy endpoints compared with patients receiving placebo (Table 1). Improvements in efficacy endpoints were also seen in the riociguat 1.5mg‐maximum group. Four (11%) patients reported SAEs during PATENT‐1; none were considered drug‐related. One patient died owing to right ventricular failure and worsening PAH (riociguat 1.5mg‐maximum group; not considered drug‐related) and two patients discontinued treatment; one owing to supraventricular tachycardia and hypotension (riociguat 2.5mg‐maximum group; considered drug‐related) and one owing to pneumothorax (placebo group; not considered drug‐related). In the PATENT‐2 open‐label extension (median treatment duration 139 weeks), the improvements in 6MWD and WHOFC observed in PATENT‐1 persisted for up to 2 years. Conclusions: In PATENT‐1 and PATENT‐2, riociguat improved a range of clinical outcomes in patients with persistent or recurrent PAH after complete surgical repair of CHD. (Table Presented).