Long-term Results with Riociguat Therapy for Pulmonary Hypertension – A Single Center Canadian Experience

Riociguat is the first approved soluble guanylate cyclase stimulator. It provides a novel approach to optimizing the nitric-oxide cyclic GMP pathway in pulmonary hypertension (PH). Riociguat therapy results in symptomatic, hemodynamic and clinical outcome benefits in patients with pulmonary arterial hypertension (PAH) and subsets of chronic thromboembolic pulmonary hypertension (CTEPH). There are few reported long-term data with riociguat. We describe a 7 year experience in 65 patients (69% female) in a Canadian PH center. Incident and prevalent cases were included. Causes of PH included CTEPH (74%), idiopathic PAH (6%), connective tissue disease-PAH (14%), and PAH-other (6%). Average age was 61 for PAH and 63 for CTEPH. All PAH patients were on at least one other (endothelin antagonist or prostanoid) background therapy, while 69% of CTEPH patients were treatment naive. Mean duration of therapy in PAH was 35 months (range 1-77), and 19.6 months (1-80) for CTEPH. Riociguat was uptitrated every 2 weeks from 1.0 mg TID to a maximum of 2.5 mg TID. 95% of patients achieved the maximum dose. Minor side effects were typical of PAH therapy. Reasons for discontinuation included for PAH: GI side effects (n=1) and no clinical benefit (n-3); and for CTEPH: death (n=1), pulmonary hemorrhage (n=1), nosebleed (n=1), no clinical benefit (n=3) and pulmonary thromboendarterectomy surgery (n=2). At baseline, in PAH, 35% were in WHO functional class (FC) 2 and 65% FC3. At 15 months 78% were in FC 2 and 23 in FC 3. For CTEPH, at baseline, 75% were in FC3 and 25% FC2. After 15 months, 77% were in FC2 and 23% in FC3. By Kaplan-Meier analysis, overall survival at 6.6 years was 72% for PAH and 98% for CTEPH. Event-free survival was 63% for PAH and 71% for CTEPH. Riociguat is safe and effective, and its uptitration is easily manageable.