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

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-naive 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-naive 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-naive 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-naive 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-naive 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.