Change in REVEAL Lite 2 risk score predicts outcomes in patients with pulmonary arterial hypertension in the PATENT study.


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:
03 2022
Historique:
received: 20 12 2020
revised: 24 09 2021
accepted: 20 10 2021
pubmed: 2 12 2021
medline: 1 4 2022
entrez: 1 12 2021
Statut: ppublish

Résumé

Risk assessment is essential in pulmonary arterial hypertension (PAH) management. We investigated the effect of riociguat on REVEAL Lite 2 score, an abridged version of the REVEAL risk score, and its association with long-term outcomes in PATENT. PATENT-1 was a randomized, double-blind study of riociguat vs placebo in patients with PAH. In the PATENT-2 open-label extension, all patients received riociguat up to 2.5 mg three times daily (n = 396). REVEAL Lite 2 scores were calculated at baseline, PATENT-1 Week 12, and PATENT-2 Week 12, with patients stratified as low- (1-5), intermediate- (6-7), or high-risk (≥8). Kaplan-Meier and Cox proportional hazards analyses assessed association of riociguat with survival and clinical worsening-free survival (CWFS). REVEAL Lite 2 score improved with riociguat 2.5 mg at PATENT-1 Week 12 (least-squares mean difference vs placebo: -0.8; p = 0.0004). More patients receiving riociguat 2.5 mg stabilized or improved risk stratum at PATENT-1 Week 12 vs placebo (p = 0.0005) and achieved low-risk status. REVEAL Lite 2 score at baseline and PATENT-1 Week 12 were associated with survival and CWFS (all p < 0.0001), as was change in score from baseline to Week 12 (p = 0.0002 and p < 0.0001, respectively). Survival and CWFS differed between risk strata at baseline (p < 0.0001) and PATENT-1 Week 12 (p < 0.0001). This analysis confirms the risk-reduction benefits of riociguat in patients with PAH and further contributes to the validation of REVEAL Lite 2 in facilitating PAH risk assessment.

Sections du résumé

BACKGROUND
Risk assessment is essential in pulmonary arterial hypertension (PAH) management. We investigated the effect of riociguat on REVEAL Lite 2 score, an abridged version of the REVEAL risk score, and its association with long-term outcomes in PATENT.
METHODS
PATENT-1 was a randomized, double-blind study of riociguat vs placebo in patients with PAH. In the PATENT-2 open-label extension, all patients received riociguat up to 2.5 mg three times daily (n = 396). REVEAL Lite 2 scores were calculated at baseline, PATENT-1 Week 12, and PATENT-2 Week 12, with patients stratified as low- (1-5), intermediate- (6-7), or high-risk (≥8). Kaplan-Meier and Cox proportional hazards analyses assessed association of riociguat with survival and clinical worsening-free survival (CWFS).
RESULTS
REVEAL Lite 2 score improved with riociguat 2.5 mg at PATENT-1 Week 12 (least-squares mean difference vs placebo: -0.8; p = 0.0004). More patients receiving riociguat 2.5 mg stabilized or improved risk stratum at PATENT-1 Week 12 vs placebo (p = 0.0005) and achieved low-risk status. REVEAL Lite 2 score at baseline and PATENT-1 Week 12 were associated with survival and CWFS (all p < 0.0001), as was change in score from baseline to Week 12 (p = 0.0002 and p < 0.0001, respectively). Survival and CWFS differed between risk strata at baseline (p < 0.0001) and PATENT-1 Week 12 (p < 0.0001).
CONCLUSIONS
This analysis confirms the risk-reduction benefits of riociguat in patients with PAH and further contributes to the validation of REVEAL Lite 2 in facilitating PAH risk assessment.

Identifiants

pubmed: 34848133
pii: S1053-2498(21)02572-9
doi: 10.1016/j.healun.2021.10.013
pii:
doi:

Substances chimiques

Pyrazoles 0
Pyrimidines 0
riociguat RU3FE2Y4XI

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

411-420

Informations de copyright

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

Auteurs

Raymond L Benza (RL)

Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio. Electronic address: Raymond.Benza@osumc.edu.

Athénaïs Boucly (A)

Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France.

Harrison W Farber (HW)

Pulmonary Hypertension Center, Boston University/Boston Medical Center, Boston, Massachusetts.

Adaani E Frost (AE)

Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas.

Hossein-Ardeschir Ghofrani (HA)

Department of Medicine, University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany; Imperial College London, London, UK; Department of Pneumology, Kerckhoff-Klinik, Bad Nauheim, Germany.

Marius M Hoeper (MM)

Department of Respiratory Medicine and the German Center for Lung Research, Hannover Medical School, Hannover, Germany.

Marc Lambelet (M)

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

Claudia Rahner (C)

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

Sameer Bansilal (S)

US Medical Affairs, Bayer Corporation, Whippany, New Jersey.

Sylvia Nikkho (S)

Global Clinical Development, Bayer AG, Berlin, Germany.

Christian Meier (C)

Global Medical Affairs, Bayer AG, Berlin, Germany.

Olivier Sitbon (O)

Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France.

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Classifications MeSH