Effect of Riociguat on Pulmonary Arterial Compliance in Patients With Pulmonary Arterial Hypertension (PAH) in the Respite Study

Abstract

SESSION TITLE: Pulmonary Hypertension - Advances in Management and Therapy SESSION TYPE: Original Investigation Slide PRESENTED ON: Tuesday, October 31, 2017 at 02:45 PM - 04:15 PM PURPOSE: Pulmonary arterial compliance (PAC) is defined as stroke volume/(systolic pulmonary arterial pressure-diastolic pulmonary arterial pressure) and is a measure of pulmonary stiffness and a physiological sign of ventricular afterload. This post hoc analysis of data from patients with PAH in the RESPITE (Riociguat clinical Effects Studied in Patients with Insufficient Treatment response to PDE5 inhibitors) study aimed to assess the effect on PAC of switching from phosphodiesterase type 5 inhibitors (PDE5i) to riociguat. METHODS: RESPITE (NCT02007629) was a prospective, multicenter, uncontrolled, open-label, single-arm, Phase IIIb trial. Sixty-one patients with PAH were enrolled based on prespecified criteria indicating they had an insufficient response to PDE5i therapy. Following a 1-3-day PDE5i treatment-free period, riociguat was adjusted to the optimal dose (up to 2.5 mg three times daily). Right heart catheterization was performed at baseline and at Week 24. RESULTS: At baseline, mean (standard deviation) PAC was 1.22 (0.62) mL/mmHg (n=59) which had increased by 0.22 (0.64) mL/mmHg (n=48) (95% CI 0.036-0.407; p=0.02) at Week 24. Patients who achieved WHO functional class (FC) I/II at Week 24 (n=26) showed an increase in PAC from baseline of 0.41 (0.68) mL/mmHg. However, those patients who remained in WHO FC III (n=22) showed no change (+0.002 [0.51] mL/mmHg). Additionally, the 16 patients who met the combined endpoint at Week 24 of freedom from clinical worsening, achievement of WHO FC I/II, and a ≥30 m improvement in 6-minute walking distance (6MWD), also had a greater improvement in PAC (+0.55 [0.81] mL/mmHg) than the 32 patients not achieving this endpoint (+0.06 [0.46] mL/mmHg). The change from baseline in PAC correlated significantly with change from baseline in cardiac index (r=0.46, p=0.0009), mean pulmonary arterial pressure (r=-0.55, p<0.0001), and pulmonary vascular resistance (r=-0.55, p<0.0001). No significant correlations were observed between change from baseline in PAC and in 6MWD or N-terminal prohormone of brain natriuretic peptide. CONCLUSIONS: In the RESPITE trial, riociguat was found to improve PAC in patients with PAH who had switched from PDE5i. CLINICAL IMPLICATIONS: This post hoc analysis demonstrates the clinical relevance of assessing PAC for a more complete assessment of right ventricular function, and suggests that determination of PAC may help to predict outcomes in patients with PAH. DISCLOSURE: Thenappan Thenappan: Grant monies (from sources other than industry): American Heart Association, Fiduciary position (of any organization, association, society, etc, other than ACCP: Nominal consultant fee from Gilead and Actelion Marius Hoeper: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, Gilead, GSK, Pfizer, MSD - Lectures and consultations Paul Corris: Grant monies (from industry related sources): Bayer - University Research Fund, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Actelion, GSK Hossein-Ardeschir Ghofrani: Grant monies (from industry related sources): Actelion, Bayer, Pfizer, Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Pfizer, Bellerophon Therapeutics - Board membership, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Pfizer, Bellerophon Therapeutics, United Therapeutics - Consultancy, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Pfizer, United Therapeutics - Paid lectures, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Pfizer, United Therapeutics - Travel/accomodation expenses James Klinger: Other: Actelion, Bayer, Gilead Sciences, Ikaria, Lung Biotechnology, NH-NHLBI, Pfizer, United Therapeutics - Research support , Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Bayer David Langleben: Consultant fee, speaker bureau, advisory committee, etc.: Bayer Healthcare Pharmaceuticals, Actelion, Gilead, GSK, Ikaria - Personal fees, Other: Bayer Healthcare Pharmaceuticals, Actelion, Gilead, GSK, Ikaria - Non-Financial Support Robert Naeije: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, GSK - Personal Fees, Grant monies (from industry related sources): Reata, Other: Actelion, Bayer, Lung Biotechnology Corporation - Advisory Board Member Fees Gérald Simonneau: Grant monies (from industry related sources): Actelion, Bayer, GSK, Novartis, Lilly, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, GSK, Novartis, Lilly, Other: Pfizer - Non-Financial Support Pavel Jansa: Other: Actelion, Bayer AG - Investigator, Consultant fee, speaker bureau, advisory committee, etc.: Bayer AG, AOP Stephan Rosenkranz: Grant monies (from industry related sources): Actelion, Bayer, Novartis, Pfizer, United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Bayer, Gilead, GSK, Novartis, Pfizer, United Therapeutics Ekkehard Grünig: Grant monies (from industry related sources): Bayer, Actelion, GSK, Lilly, Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Miltenyi, Novartis, United Therapeutics, Other: Alexion - Non-Financial Support Christian Meier: Employee: Bayer AG Dennis Busse: Employee: Chrestos Concept GmbH & Co. KG Raymond Benza: Grant monies (from industry related sources): Bayer AG The following authors have nothing to disclose: Laura Scelsi No Product/Research Disclosure Information