Initial Riociguat Monotherapy and Transition from Sildenafil to Riociguat in Patients with Idiopathic Pulmonary Arterial Hypertension: Influence on Right Heart Remodeling and Right Ventricular–Pulmonary Arterial Coupling

• Published in: Lung 2018-12, Vol.196 (6), p.745-753
• Main Authors: Taran, Irina N., Belevskaya, Anna A., Saidova, Marina A., Martynyuk, Tamila V., Chazova, Irina E.
• Format: Article
• Language: English
• Subjects: Adult; Atrial Remodeling; Care and treatment; Coupling; Development and progression; Drug Substitution; Drug therapy; Echocardiography; Enzyme Activators - adverse effects; Enzyme Activators - therapeutic use; Familial Primary Pulmonary Hypertension - diagnostic imaging; Familial Primary Pulmonary Hypertension - drug therapy; Familial Primary Pulmonary Hypertension - physiopathology; Female; Functional morphology; Heart; Heart Atria - diagnostic imaging; Heart Atria - physiopathology; Heart Ventricles - diagnostic imaging; Heart Ventricles - physiopathology; Humans; Hypertension; Male; Medicine; Medicine & Public Health; Middle Aged; Patient outcomes; Patients; Pilot Projects; Pneumology/Respiratory System; Pulmonary Artery - physiopathology; Pulmonary Hypertension; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Sildenafil; Sildenafil Citrate - therapeutic use; Subgroups; Therapy; Ventricle; Ventricular Remodeling; Walk Test
• ISSN: 0341-2040; 1432-1750
• DOI: 10.1007/s00408-018-0160-4

Purpose To evaluate the influence of riociguat on World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), right heart remodeling, and right ventricular–pulmonary arterial (RV–PA) coupling in patients with idiopathic pulmonary arterial hypertension (IPAH) who are treatment-naïve or who have failed to achieve treatment goals with sildenafil therapy. Methods Twenty patients with IPAH were enrolled: 12 had not previously received PAH-targeted therapy (treatment-naïve subgroup) and 8 had been receiving sildenafil therapy but failed to achieve treatment goals; on entering this pilot study these 8 patients were switched from sildenafil to riociguat therapy (treatment-switch subgroup). Patients received riociguat individually dose-adjusted up to a maximum of 2.5 mg three times daily. After 12 weeks, patients were assessed for WHO FC, 6MWD, right heart remodeling, and RV–PA coupling. Results Riociguat significantly improved WHO FC in treatment-naïve patients (from 0/4/8/0 patients in WHO I/II/III/IV at baseline to 1/6/5/0 at week 12) and in treatment-switch patients (from 0/4/4/0 patients in WHO I/II/III/IV at baseline to 1/4/3/0 at week 12). Additionally, treatment-naïve and treatment-switch patients showed significant improvements at week 12 versus baseline in 6MWD (increases of + 76.8 m and + 71.6 m, respectively), RV systolic function, and RV–PA coupling. Conclusion These results support the proven efficacy of riociguat in patients with IPAH, including treatment-naïve patients and those switching to riociguat following failure to achieve treatment goals with sildenafil, and suggest that it may be possible to delay disease progression in this patient group.