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


Journal

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
ISSN: 1557-3117
Titre abrégé: J Heart Lung Transplant
Pays: United States
ID NLM: 9102703

Informations de publication

Date de publication:
10 2021
Historique:
received: 06 01 2021
revised: 11 06 2021
accepted: 28 06 2021
pubmed: 7 8 2021
medline: 17 2 2022
entrez: 6 8 2021
Statut: ppublish

Résumé

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

Sections du résumé

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.

Identifiants

pubmed: 34353714
pii: S1053-2498(21)02399-8
doi: 10.1016/j.healun.2021.06.020
pii:
doi:

Substances chimiques

Enzyme Activators 0
Pyrazoles 0
Pyrimidines 0
riociguat RU3FE2Y4XI

Banques de données

ClinicalTrials.gov
['NCT00863681', 'NCT00910429', 'NCT00810693']

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1172-1180

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Raymond L Benza (RL)

Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Ohio, USA. Electronic address: Raymond.benza@osumc.edu.

Hossein-Ardeschir Ghofrani (HA)

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.

Ekkehard Grünig (E)

Centre for Pulmonary Hypertension, Thoraxklinik at Heidelberg University Hospital, German Center of Lung Research (DZL), Heidelberg, Germany.

Marius M Hoeper (MM)

Department of Respiratory Medicine, Hannover Medical School, German Center of Lung Research (DZL), Hannover, Germany.

Pavel Jansa (P)

2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Zhi-Cheng Jing (ZC)

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.

Nick H Kim (NH)

Division of Pulmonary and Critical Care Medicine, University of California San Diego, La Jolla, California.

David Langleben (D)

Centre for Pulmonary Vascular Disease and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.

Gérald Simonneau (G)

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.

Chen Wang (C)

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.

Dennis Busse (D)

Employee of Chrestos Concept GmbH & Co. KG, Essen, Germany.

Christian Meier (C)

Global Medical Affairs, Bayer AG, Berlin, Germany.

Stefano Ghio (S)

Division of Cardiology, Fondazione IRCCS Policlinico S Matteo, Pavia, Italy.

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Classifications MeSH