Effect of riociguat on pulmonary arterial compliance in the PATENT and CHEST studies

Thenappan Thenappan; Nadine Al-Naamani; Stefano Ghio; Hossein-Ardeschir Ghofrani; Paul M Hassoun; Marc Pritzker; Adam Torbicki; Sylvia Nikkho; Dennis Busse; Ioana R Preston

doi:10.1177/2045894020963836

Effect of riociguat on pulmonary arterial compliance in the PATENT and CHEST studies

Pulm Circ. 2020 Nov 20;10(4):2045894020963836. doi: 10.1177/2045894020963836. eCollection 2020 Oct-Dec.

Authors

Affiliations

¹ Division of Cardiology, University of Minnesota, Minneapolis, MN, USA.
² Pulmonary, Critical Care and Sleep Division, University of Pennsylvania, Philadelphia, PA, USA.
³ Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, University Hospital, Pavia, Italy.
⁴ Department of Medicine, University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.
⁵ German Center of Lung Research (DZL), Giessen, Germany.
⁶ Department of Medicine, Imperial College London, London, UK.
⁷ Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Pulmonary Circulation and Thromboembolic Diseases, Center of Postgraduate Medical Education, ECZ-Otwock, Otwock, Poland.
⁹ Global Clinical Development, Bayer AG, Berlin, Germany.
¹⁰ Chrestos Concept GmbH & Co. KG, Essen, Germany.
¹¹ Pulmonary, Critical Care and Sleep Division, Tufts University Medical Center, Boston, MA, USA.

Abstract

Pulmonary arterial compliance is a measure of the pulsatile afterload of the right ventricle. Lower pulmonary arterial compliance is associated with reduced right ventricular function and worse prognosis in pulmonary hypertension. The effect of pulmonary vasodilators on pulmonary arterial compliance has not been evaluated in detail in pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In this post hoc analysis of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the PATENT and CHEST studies, we evaluated the change in pulmonary arterial compliance with riociguat versus placebo. Association of pulmonary arterial compliance with clinical outcomes was assessed using Kaplan-Meier and Cox proportional hazards analyses. Compared with placebo, riociguat significantly improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline was associated with survival and clinical worsening-free survival in pulmonary arterial hypertension but only with clinical worsening-free survival in chronic thromboembolic pulmonary hypertension. In patients with pulmonary arterial hypertension, pulmonary arterial compliance at follow-up ≥1.6 mL/mmHg was associated with better outcomes than pulmonary arterial compliance <1.6 mL/mmHg. In patients with chronic thromboembolic pulmonary hypertension, pulmonary arterial compliance at follow-up did not predict outcomes. Cox proportional hazards analyses showed no association between change in pulmonary arterial compliance and outcomes in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In conclusion, riociguat improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline or follow-up, rather than change in pulmonary arterial compliance, is of prognostic importance for outcomes.

Keywords: chronic thromboembolic pulmonary hypertension; pulmonary arterial hypertension; pulmonary hemodynamics; pulmonary hypertension; riociguat.

Grants and funding

K23 HL141584/HL/NHLBI NIH HHS/United States