Effect of riociguat on right ventricular function in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

Raymond L Benza; Hossein-Ardeschir Ghofrani; Ekkehard Grünig; Marius M Hoeper; Pavel Jansa; Zhi-Cheng Jing; Nick H Kim; David Langleben; Gérald Simonneau; Chen Wang; Dennis Busse; Christian Meier; Stefano Ghio

doi:10.1016/j.healun.2021.06.020

Effect of riociguat on right ventricular function in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

J Heart Lung Transplant. 2021 Oct;40(10):1172-1180. doi: 10.1016/j.healun.2021.06.020. Epub 2021 Jul 10.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Ohio, USA. Electronic address: Raymond.benza@osumc.edu.
² University of Giessen and Marburg Lung Center, German Center of Lung Research (DZL), Giessen, Germany; Department of Pneumology, Kerckhoff-Klinik, Bad Nauheim, Germany; Department of Medicine, Imperial College London, London, UK.
³ Centre for Pulmonary Hypertension, Thoraxklinik at Heidelberg University Hospital, German Center of Lung Research (DZL), Heidelberg, Germany.
⁴ Department of Respiratory Medicine, Hannover Medical School, German Center of Lung Research (DZL), Hannover, Germany.
⁵ 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
⁶ Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁷ Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, California.
⁸ Centre for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
⁹ Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation, Hôpital Bicêtre, Université Paris-Saclay, Le Kremlin-Bicêtre, France; INSERM UMR_S999, LabEx LERMIT, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
¹⁰ Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; National Clinical Research Center for Respiratory Diseases, Beijing, China; Chinese Academy of Medical Sciences, Peking Union Medica, Beijing, China; WHO Collaboration Center for Tobacco Cessation and Respiratory Diseases Prevention, Beijing, China.
¹¹ Employee of Chrestos Concept GmbH & Co. KG, Essen, Germany.
¹² Global Medical Affairs, Bayer AG, Berlin, Germany.
¹³ Division of Cardiology, Fondazione IRCCS Policlinico S Matteo, Pavia, Italy.

PMID: 34353714
DOI: 10.1016/j.healun.2021.06.020

Abstract

Background: In the Phase III PATENT-1 (NCT00810693) and CHEST-1 (NCT00855465) studies, riociguat demonstrated efficacy vs placebo in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Clinical effects were maintained at 2 years in the long-term extension studies PATENT-2 (NCT00863681) and CHEST-2 (NCT00910429).

Methods: This post hoc analysis of hemodynamic data from PATENT-1 and CHEST-1 assessed whether riociguat improved right ventricular (RV) function parameters including stroke volume index (SVI), stroke volume, RV work index, and cardiac efficiency. REVEAL Risk Score (RRS) was calculated for patients stratified by SVI and right atrial pressure (RAP) at baseline and follow-up. The association between RV function parameters and SVI and RAP stratification with long-term outcomes was assessed.

Results: In PATENT-1 (n = 341) and CHEST-1 (n = 238), riociguat improved RV function parameters vs placebo (p < 0.05). At follow-up, there were significant differences in RRS between patients with favorable and unfavorable SVI and RAP, irrespective of treatment arm (p < 0.0001). Multiple RV function parameters at baseline and follow-up were associated with survival and clinical worsening-free survival (CWFS) in PATENT-2 (n = 396; p < 0.05) and CHEST-2 (n = 237). In PATENT-2, favorable SVI and RAP at follow-up only was associated with survival and CWFS (p < 0.05), while in CHEST-2, favorable SVI and RAP at baseline and follow-up were associated with survival and CWFS (p < 0.05).

Conclusion: This post hoc analysis of PATENT and CHEST suggests that riociguat improves RV function in patients with PAH and CTEPH.

Keywords: CTEPH; PAH; hypertension, pulmonary; ventricular function, right.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Atrial Pressure / drug effects*
Enzyme Activators / administration & dosage
Female
Follow-Up Studies
Humans
Hypertension, Pulmonary / drug therapy*
Hypertension, Pulmonary / etiology
Hypertension, Pulmonary / physiopathology
Male
Middle Aged
Pulmonary Embolism / complications*
Pyrazoles / administration & dosage*
Pyrimidines / administration & dosage*
Stroke Volume / physiology*
Treatment Outcome
Ventricular Function, Right / drug effects*

Substances

Enzyme Activators
Pyrazoles
Pyrimidines
riociguat

Associated data

ClinicalTrials.gov/NCT00863681
ClinicalTrials.gov/NCT00910429
ClinicalTrials.gov/NCT00810693