Keiko Yamamoto1, Nobuhiro Tanabe2, Rika Suda3, Akane Sasaki4, Akane Matsumura4, Ryogo Ema4, Hajime Kasai4, Fumiaki Kato4, Ayumi Sekine2, Rintaro Nishimura2, Takayuki Jujo2, Toshihiko Sugiura4, Ayako Shigeta4, Seiichiro Sakao4, Koichiro Tatsumi4. 1. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. Electronic address: shiitake@mx7.ttcn.ne.jp. 2. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; Department of Advanced Medicine in Pulmonary Hypertension, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. 3. Department of Advanced Medicine in Pulmonary Hypertension, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. 4. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Abstract
BACKGROUND: Riociguat, the first approved drug for patients with chronic thromboembolic pulmonary hypertension (CTEPH), is a soluble guanylate cyclase (sGC) Stimulator. It directly stimulates sGC independently of nitric oxide (NO) and increases sGC sensitivity for NO. The safety and efficacy of transitioning from a phosphodiesterase 5 inhibitor (PDE5i) to riociguat is unknown. METHODS AND RESULTS: Twenty-three patients were prospectively enrolled: 8 symptomatic patients with inadequate clinical responses to PDE5i were changed to riociguat (transitioned group); 15 started riociguat anew (new or add-on group). We analyzed the change from baseline to 6-12 months of riociguat treatment for the 6-minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI), partial pressure of oxygen in arterial blood (PaO2), brain natriuretic peptide (BNP), World Health Organization (WHO) functional class, safety and adverse events. The mPAP, BNP and WHO functional class significantly improved in total. In the transitioned group, BNP significantly decreased by -116.5±188.6pg/ml (P=0.0156). The 6MWD, mPAP, PVR, CI, and PaO2 improved but not significantly. The baseline condition was significantly more severe in the transitioned than in the new or add-on group. No patients discontinued riociguat. Relatively rapid transitioning from PDE5i to riociguat was safe under careful observation. CONCLUSIONS: Transitioning to riociguat may be safe and effective in CTEPH patients with inadequate clinical responses to PDE5i.
BACKGROUND:Riociguat, the first approved drug for patients with chronic thromboembolic pulmonary hypertension (CTEPH), is a soluble guanylate cyclase (sGC) Stimulator. It directly stimulates sGC independently of nitric oxide (NO) and increases sGC sensitivity for NO. The safety and efficacy of transitioning from a phosphodiesterase 5 inhibitor (PDE5i) to riociguat is unknown. METHODS AND RESULTS: Twenty-three patients were prospectively enrolled: 8 symptomatic patients with inadequate clinical responses to PDE5i were changed to riociguat (transitioned group); 15 started riociguat anew (new or add-on group). We analyzed the change from baseline to 6-12 months of riociguat treatment for the 6-minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI), partial pressure of oxygen in arterial blood (PaO2), brain natriuretic peptide (BNP), World Health Organization (WHO) functional class, safety and adverse events. The mPAP, BNP and WHO functional class significantly improved in total. In the transitioned group, BNP significantly decreased by -116.5±188.6pg/ml (P=0.0156). The 6MWD, mPAP, PVR, CI, and PaO2 improved but not significantly. The baseline condition was significantly more severe in the transitioned than in the new or add-on group. No patients discontinued riociguat. Relatively rapid transitioning from PDE5i to riociguat was safe under careful observation. CONCLUSIONS: Transitioning to riociguat may be safe and effective in CTEPHpatients with inadequate clinical responses to PDE5i.
Authors: Rajat Kalra; Sue Duval; Thenappan Thenappan; Ganesh Raveendran; Marc Pritzker; Sasha Z Prisco; Kurt W Prins Journal: Sci Rep Date: 2020-06-01 Impact factor: 4.379