Pulmonary Arterial Hypertension
ATS 2016. A6315 – The RESPITE Study: Riociguat in Patients with PAH and an Inadequate Response to Phosphodiesterase 5 Inhibitors
M. M. Hoeper et al.
Results: Thirty patients (mean±SD age 57±12 years; 73% female) were eligible for this interim analysis; 26 (87%) completed the study. Patients were pretreated with sildenafil (n=21) or tadalafil (n=9); 22 (73%) also received an ERA. At baseline, all patients were in FC III; by Week 24, 50% had improved to FC II. From baseline to Week 24, mean±SD 6MWD increased from 353±78 m to 392±112 m (n=25); mean±SD pulmonary vascular resistance decreased from 856±266 dyn•sec•cm-5 to 772±465 dyn•sec•cm-5 (n=25); mean±SD cardiac index increased from 2.2±0.3 L/min/m2 to 2.6±0.6 L/min/m2 (n=25); and mean±SD NT-proBNP levels decreased from 2208±2961 pg/mL to 817±1066 pg/mL (n=26). Four patients (13%) experienced clinical worsening events, including 3 deaths: one patient died from subdural hematoma after a fall and one patient died from pneumonia, neither of which were considered study drug-related; the other patient died from an unknown cause during the extension period of the study. The most frequent study drug-related adverse events were headache (17%), dyspepsia (13%), epistaxis (13%), and dizziness (10%).
Conclusions: In this interim analysis of RESPITE, riociguat improved 6MWD, hemodynamics, NT-proBNP levels, and WHO FC in PAH patients previously treated with PDE5i. No new safety signals were observed. These preliminary data support the hypothesis that patients with PAH who have an insufficient response to PDE5i therapy may benefit from a transition to riociguat. Randomized controlled trials are required to further investigate this approach.
CARE™ FACULTY PERSPECTIVE: Riociguat is a stimulator of soluble guanylate cyclase, the receptor for nitric oxide (NO), and is approved in Canada for the management of inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The RESPITE study is an open-label, international, multicenter, single-arm, uncontrolled, phase IIIb study of riociguat in patients with pulmonary arterial hypertension (PAH) with insufficient response to treatment with Phosphodiesterase-5 inhibitors (PDE-5i). The interim analysis of RESPITE that was presented at ATS suggests efficacy of riociguat in these patients with PAH.