Riociguat for pulmonary arterial hypertension associated with congenital heart disease

Objective The Pulmonary Arterial hyperTENsion sGC-stimulator Trial-1 (PATENT-1) was a randomised, doubleblind, placebo-controlled phase III trial evaluating riociguat in patients with pulmonary arterial hypertension (PAH). PATENT-2 was an open-label long-term extension to PATENT-1. Here, we explore the efficacy and safety of riociguat in the subgroup of patients with persistent/recurrent PAH after correction of congenital heart disease (PAH-CHD) from the PATENT studies. Methods In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo for 12 weeks; efficacy assessments included change from baseline to study end in 6-min walking distance (6MWD; primary), pulmonary vascular resistance (PVR), N-terminal of the prohormone of brain natriuretic peptide (NT-proBNP), WHO functional class (WHO FC) and time to clinical worsening. In PATENT-2, eligible patients from PATENT-1 received long-term riociguat (maximum 2.5 mg three times daily); the primary assessment was safety and tolerability. All PAH-CHD patients had a corrected cardiac defect. Results In PATENT-1, riociguat increased mean+/-SD 6MWD from baseline to week 12 by 39+/-60 m in patients with PAH-CHD versus 0+/-42 m for placebo. Riociguat also improved several secondary variables versus placebo, including PVR (-250+/-410 vs -66+/-632 dyn.s/cm(5)), NT-proBNP (-164+/-317 vs -46+/-697 pg/mL) and WHO FC (21%/79%/0% vs 8%/83%/8% improved/stabilised/worsened). One patient experienced clinical worsening (riociguat 1.5 mg group). Riociguat was well tolerated. In PATENT-2, riociguat showed sustained efficacy and tolerability in patients with PAH-CHD at 2 years. Conclusions Riociguat was well tolerated in patients with PAH-CHD and improved clinical outcomes including 6MWD, PVR, WHO FC and NT-proBNP.