Riociguat in Adults With Congenital Heart Disease and Pulmonary Hypertension

Study Questions:

What is the efficacy and safety of riociguat in patients with recurrent pulmonary hypertension after correction of congenital heart disease?


This manuscript reports a post-hoc analysis of data from the Pulmonary Arterial hyperTENsion sGC-stimulator (PATENT)-1 and PATENT-2 trials, which prospectively studied riociguat in adults with pulmonary arterial hypertension (PAH). The PATENT-1 trial was a randomized, double-blinded, placebo-controlled phase III trial with duration of 12 weeks, while the PATENT-2 trial was an open-label long-term extension trial. A total of 35 patients with congenital heart disease (CHD) and PAH were enrolled in PATENT-1, of which 33 also participated in PATENT-2. Efficacy assessments included change in 6-minute walking distance (6MWD), pulmonary vascular resistance (PVR), N-terminal of the prohormone of brain natriuretic peptide (NT-proBNP), World Health Organization (WHO) functional class, and time to functional worsening.


In PATENT-1, riociguat increased mean ± standard deviation (SD) 6MWD from baseline to week 12 by 39 ± 60 m as compared with stable 6MWD in the placebo group (0 ± 42 m). Riociguat also improved secondary variables, including PVR (-250 ± 410 vs. -66 ± 632 dyn·s/cm5) and NT-proBNP (-164 ± 317 vs. -46 ± 697 pg/ml). In PATENT-2, riociguat showed sustained efficacy in patients with CHD and PAH at 2 years.


Riociguat was well-tolerated in adults with CHD and PAH, and was associated with improved outcomes including 6MWD, PVR, WHO functional class, and NT-proBNP.


Riociguat is a novel stimulator of soluble guanylate cyclase (sGC). Riociguat acts both to sensitize sGC to endogenous nitric oxide (NO) by stabilizing NO-sGC binding, as well as to directly stimulate sGC via a different binding site, independently of NO. PAH is increasingly understood to be an important late complication after repair of congenital heart defects. This study enrolled patients with a mean age of 38 years, at a mean of 17 years after their procedure. The study was limited to patients with relatively simple CHD (atrial septal defect, ventricular septal defect, and patent ductus arteriosus), which was repaired relatively late in life. As this was a post-hoc analysis of a relatively small number of patients, it is difficult to be sure of the benefit of riociguat over placebo. However, this study is promising in suggesting both safety and efficacy of riociguat to be similar to that reported for the general study population of PATENT-1 and -2.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD & Pediatrics, Cardiac Surgery and Heart Failure, Congenital Heart Disease, CHD & Pediatrics and Arrhythmias, CHD & Pediatrics and Prevention, Statins, Heart Failure and Cardiac Biomarkers, Pulmonary Hypertension, Hypertension

Keywords: Blood Pressure, Ductus Arteriosus, Patent, Guanylate Cyclase, Heart Defects, Congenital, Heart Septal Defects, Atrial, Heart Septal Defects, Ventricular, Hypertension, Hypertension, Pulmonary, Natriuretic Peptide, Brain, Primary Prevention, Pyrazoles, Pyrimidines, Vascular Diseases, Vascular Resistance

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