Riociguat in Combination With Endothelin Receptor Antagonists (ERAs) for the Treatment of Pulmonary Arterial Hypertension (PAH): A Subgroup Analysis of PATENT

Abstract

PURPOSE: The ACCP suggests that riociguat may be added to the treatment regimen of PAH patients who remain symptomatic despite stable regimens of an inhaled prostanoid or an ERA. PATENT‐1 (the Pulmonary Arterial Hypertension Soluble Guanylate Cyclase‐Stimulator Trial) allowed patients to enroll while on stable regimens of ERAs. Here, we report findings from analysis of the subgroup of patients from the PATENT trial who were on background ERA therapy (BERA). METHODS: Patients were assigned to placebo (N=126; n=54 on BERA), to individualized dosing of riociguat up to 2.5 mg TID (N=254; n=113 on BERA), or to an exploratory riociguat group capped at 1.5 mg TID (N=63; n=27 on BERA). Primary outcome was change from baseline (BL) in 6minute walk distance (6MWD) at week 12. Secondary exploratory outcomes included change from BL in pulmonary vascular resistance (PVR), NT‐proBNP, WHO functional class (WHO‐FC), and clinical worsening. RESULTS: All apply to patients (riociguat and placebo) on BERA. For the placebo‐corrected mean change from baseline to last visit, 6MWD in riociguat patients (1.0 to 2.5 mg TID) increased by 26 meters (95% CI: 5‐46 meters). Mean change in PVR for riociguat patients was ‐174±202 dyn•s•cm‐5, versus ‐46±266 dyn•s•cm‐5 for placebo. Mean change in NT‐proBNP was 90±2212 pg/mL for riociguat patients versus 172±759 pg/mL for placebo. By last visit, 26% of riociguat patients had improved one WHO‐FC (71% maintained FC, while 4% worsened 1 FC) compared with 13% of placebo patients (76% maintained FC, and 9% and 2% worsened 1 and 2 FC, respectively). Among riociguat patients, only 1 (0.9%) had at least 1 clinical worsening event, compared with 3 (5.6%) among placebo patients, including 1 death. CONCLUSIONS: These data suggest that adding riociguat to stable regimens of ERAs in symptomatic PAH patients has favorable effects on 6MWD, PVR, WHO‐FC, and perhaps clinical worsening. CLINICAL IMPLICATIONS: Adding riociguat to stable regimens of ERAs may be beneficial in symptomatic PAH patients but additional studies are needed to further explore this possibility.