TY - JOUR
T1 - Change in REVEAL Lite 2 risk score predicts outcomes in patients with pulmonary arterial hypertension in the PATENT study
AU - Benza, Raymond L.
AU - Boucly, Athénaïs
AU - Farber, Harrison W.
AU - Frost, Adaani E.
AU - Ghofrani, Hossein Ardeschir
AU - Hoeper, Marius M.
AU - Lambelet, Marc
AU - Rahner, Claudia
AU - Bansilal, Sameer
AU - Nikkho, Sylvia
AU - Meier, Christian
AU - Sitbon, Olivier
N1 - Funding Information:
RLB was responsible for study design; all authors were responsible for the interpretation and writing of the report and the decision to submit the article. Bayer AG, Berlin, Germany and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA participated in the study design; in the collection, analysis, and interpretation of data; in the decision to submit the report for publication. Medical writing assistance was provided by Robyn Bradbury, PhD and Rachael Powis, PhD at Adelphi Communications Ltd (Bollington, UK), funded by Bayer AG (Berlin, Germany) in accordance with Good Publications practice.
Funding Information:
RLB reports receiving grants from Actelion, Bayer AG, Bellerophon, and EIGER. AB reports non-financial support from GSK, Bayer, and MSD; and personal fees and non-financial support from Actelion. HWF reports receiving grants from Actelion, Gilead, and United Therapeutics, and receiving personal fees from Actelion, Acceleron, Altavant, Bayer AG, Bellerophon, Boehringer-Ingelheim, Gilead, and United Therapeutics. AEF is on an endpoint adjudication committee for a study funded by United Therapeutics; is currently on the Independent Data Monitoring Committee (IDMC) for two studies funded by Actelion (UNISUS and MACITEPH); and is on the steering committee reimbursement for two studies funded by Phase Bio (COVID-19 TRIAL Data and Safety Monitoring Board member [now terminated] and PAH drug trial). H-AG reports receiving grants from Actelion, Bayer AG, Ergonex, and Pfizer; personal fees from Actelion, Bayer AG, Ergonex, Pfizer, Gilead, GSK, Merck, and Novartis; and is currently on the IDMC for two studies funded by Actelion. MMH reports receiving personal fees from Acceleron, Actelion, Bayer AG, GSK, Janssen, MSD, and Pfizer. ML is an external employee of Bayer AG. CR is an external employee of Bayer AG. SB is an employee of Bayer. SN is an employee of Bayer AG. CM is an employee of Bayer AG. OS reports receiving grants, personal fees, and non-financial support from Actelion, Bayer, and MSD; grants from GSK; and personal fees from Acceleron, AOP Orphan, Ferrer, and Gossamer Bio.
Publisher Copyright:
© 2021 The Authors
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - pulmonary arterial hypertension
KW - riociguat
KW - risk assessment
KW - Double-Blind Method
KW - Pyrazoles/therapeutic use
KW - Humans
KW - Risk Factors
KW - Pulmonary Arterial Hypertension/drug therapy
KW - Treatment Outcome
KW - Pyrimidines/therapeutic use
UR - http://www.scopus.com/inward/record.url?scp=85120312219&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85120312219&partnerID=8YFLogxK
U2 - 10.1016/j.healun.2021.10.013
DO - 10.1016/j.healun.2021.10.013
M3 - Article
C2 - 34848133
AN - SCOPUS:85120312219
SN - 1053-2498
VL - 41
SP - 411
EP - 420
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 3
ER -