RT Journal Article
SR Electronic
T1 Riociguat for pulmonary arterial hypertension associated with congenital heart disease
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 1792
OP 1799
DO 10.1136/heartjnl-2015-307832
VO 101
IS 22
A1 Stephan Rosenkranz
A1 Hossein-Ardeschir Ghofrani
A1 Maurice Beghetti
A1 Dunbar Ivy
A1 Reiner Frey
A1 Arno Fritsch
A1 Gerrit Weimann
A1 Soundos Saleh
A1 Christian Apitz
YR 2015
UL http://heart.bmj.com/content/101/22/1792.abstract
AB Objective The Pulmonary Arterial hyperTENsion sGC-stimulator Trial-1 (PATENT-1) was a randomised, double-blind, 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/cm5), 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.Trial registration number The clinical trials numbers are NCT00810693 for PATENT-1 and NCT00863681 for PATENT-2.