Effect of riociguat on pulmonary arterial compliance in patients with pulmonary arterial hypertension (PAH) in the RESPITE study

Abstract

Background: Pulmonary arterial compliance (PAC), defined as stroke volume/(systolic pulmonary arterial pressure–diastolic pulmonary arterial pressure), is a measure of pulmonary artery stiffness and is a physiological sign of ventricular afterload. Aim: This post hoc analysis assessed the effect on PAC of switching from phosphodiesterase type 5 inhibitors (PDE5is) to riociguat in patients with PAH in the RESPITE study. Methods: RESPITE was a prospective, multicenter, uncontrolled, open-label, single-arm, Phase IIIb trial. Patients with PAH (n=61) were enrolled based on prespecified criteria indicating an insufficient response to PDE5i therapy. Following PDE5i washout, riociguat was adjusted to the optimal dose (maximum 2.5 mg three times daily). Right heart catheterization was performed at baseline and after 24 weeks. Results: Mean (SD) PAC at baseline was 1.22 (0.62) mL/mmHg (n=59), and had increased by 0.22 (0.64) mL/mmHg at Week 24 (n=48). PAC increased from baseline by 0.41 (0.68) mL/mmHg in the 26 patients who achieved WHO FC I/II at Week 24; however, no change was seen in the 22 patients who remained in WHO FC III (+0.002 [0.51] mL/mmHg). Similarly, patients who were free of clinical worsening at Week 24, and achieved WHO FC I/II and a ≥30 m improvement in 6MWD (n=16), had a greater increase in PAC (+0.55 [0.81] mL/mmHg) than patients not achieving this endpoint (n=32; +0.06 [0.46] mL/mmHg). Conclusion: In RESPITE, riociguat improved PAC in patients with PAH who had transitioned from PDE5i. The increase in PAC was more pronounced in patients whose exercise and functional capacity had also improved by Week 24.