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REVEAL LITE 2 RISK ASSESSMENT IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION FROM THE GRIPHON STUDY: A POST-HOC ANALYSIS DEMONSTRATES ASSOCIATION OF RISK STATUS WITH LONG-TERM OUTCOMES

      TOPIC: Pulmonary Vascular Disease
      TYPE: Original Investigations
      PURPOSE: Risk assessment is key for optimal management of patients (pts) with pulmonary arterial hypertension (PAH). REVEAL Lite 2 (RL2) is a non-invasive risk assessment tool for PAH. In this post-hoc analysis of the GRIPHON study (NCT01106014), RL2 was applied to assess its prognostic and predictive value in PAH pts randomized to selexipag, a selective IP prostacyclin receptor agonist, or placebo.
      METHODS: RL2 was used to calculate risk score and pts were categorized into low, intermediate and high-risk strata at baseline (randomization) and post-baseline timepoints. Analyses were performed to examine associations between risk category and change in risk category with long-term outcome (time to first morbidity/mortality event; MM) and the treatment effect of selexipag on long-term outcome by risk category. Hazard ratios (HR) and concordance index (C-index) were calculated using Cox proportional hazard model. Change in risk category from baseline was compared between treatment arms by proportional odds model.
      RESULTS: At baseline: overall 41% pts were low, 26% intermediate and 33% high risk; proportions were similar between treatment arms. Risk category at baseline was predictive of time to first MM: with selexipag, HR were 2.09 for intermediate vs low and 5.38 for high vs low risk; with placebo, HR were 2.41 for intermediate vs low and 3.50 for high vs low risk. C-index values at baseline, 4, 6 and 12 months, respectively were 0.68, 0.74, 0.76 and 0.73 for selexipag and 0.65, 0.67, 0.66 and 0.70 for placebo. Change in risk category correlated with change in MM rate: improvement in risk category correlated with a reduction in MM rate (HR vs no change in risk 0.43, 0.39, 0.42 at 4, 6, and 12 months, respectively); while worsened risk category correlated with an increase in MM rate (HR vs no change in risk 2.82, 3.05, 3.77 at 4, 6 and 12 months, respectively). Selexipag was approximately twice as likely to improve pts’ risk profile than placebo (odds ratio of improvement for selexipag/placebo: 2.0, 1.8, 1.9 at 4, 6, and 12 months, respectively; p<0.001 for all comparisons). Selexipag reduced the MM rate across all baseline risk categories: HR 0.57 (p=0.0178) for low, 0.42 (p=0.0001) for intermediate, and 0.71 (p=0.0326) for high-risk pts, respectively compared with placebo.
      CONCLUSIONS: RL2 risk category and change in risk category are prognostic for long-term outcome. Selexipag treatment improved risk profile and long-term outcome compared with placebo; selexipag treatment effect on long-term outcome was strongest for pts at low and intermediate risk at baseline.
      CLINICAL IMPLICATIONS: RL2 risk assessment is prognostic of long-term outcome in pts with PAH and can detect response to treatment. Simple risk assessment tools may have utility for treatment monitoring and as an endpoint in PAH clinical trials.
      DISCLOSURES: Grants relationship with Actelion Please note: 2019-2021 Added 04/29/2021 by Raymond Benza, source=Web Response, value=Grant/Research Support
      Grants relationship with Bayer AG Please note: 2019-2021 Added 04/29/2021 by Raymond Benza, source=Web Response, value=Grant/Research Support
      Grants relationship with Bellerophon Please note: 2019-2021 Added 04/29/2021 by Raymond Benza, source=Web Response, value=Grant/Research Support
      Grants relationship with EIGER Please note: 2019-2021 Added 04/29/2021 by Raymond Benza, source=Web Response, value=Grant/Research Support
      Scientific Medical Advisor relationship with Actelion Pharmaceuticals US, Inc. Please note: $1-$1000 by Kelly Chin, source=Web Response, value=Consulting fee
      Steering committee member relationship with Actelion Pharmaceuticals US, Inc. Please note: $1-$1000 by Kelly Chin, source=Web Response, value=Grant/Research Support
      Consultant relationship with United Therapeutics Please note: $1-$1000 by Kelly Chin, source=Web Response, value=Grant/Research Support
      Advisory Committee Member relationship with Bayer Healthcare Please note: $1-$1000 by Kelly Chin, source=Web Response, value=Grant/Research Support
      Advisory Committee Member relationship with Ironwood Pharmaceuticals Please note: $1-$1000 by Kelly Chin, source=Web Response, value=Grant/Research Support
      Circulation associate editor relationship with American Heart Association Please note: $1-$1000 by Kelly Chin, source=Web Response, value=Consulting fee
      Scientific Medical Advisor relationship with Actelion/Janssen Please note: Current Added 05/03/2021 by Sean Gaine, source=Web Response, value=Honoraria
      Scientific Medical Advisor relationship with United Therapeutics Please note: 2 yr Added 05/03/2021 by Sean Gaine, source=Web Response, value=Honoraria
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      Removed 05/03/2021 by Sean Gaine, source=Web Response
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      Speaker/Speaker's Bureau relationship with MSD Please note: $1-$1000 by Nazzareno Galie, source=Web Response, value=Consulting fee
      Removed 05/03/2021 by Nazzareno Galie, source=Web Response
      Grant/research support to my institution relationship with Actelion Pharmaceuticals Ltd Please note: $5001 - $20000 by Nazzareno Galie, source=Web Response, value=Grant/Research Support
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      Removed 05/03/2021 by Nazzareno Galie, source=Web Response
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      Removed 05/03/2021 by Nazzareno Galie, source=Web Response
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      Advisory Committee Member relationship with Actelion Please note: $1001 - $5000 by Nazzareno Galie, source=Web Response, value=Consulting fee
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      Consultant relationship with Acceleron Please note: $1001 - $5000 by Marius Hoeper, source=Web Response, value=Honoraria
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      Consultant relationship with Bayer AG Please note: $1001 - $5000 by Marius Hoeper, source=Web Response, value=Honoraria
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      Consultant relationship with Pfizer Please note: $1001 - $5000 by Marius Hoeper, source=Web Response, value=Honoraria
      Speaker/Speaker's Bureau relationship with Actelion Please note: $1-$1000 by Irene Lang, source=Web Response, value=Honoraria
      Scientific Medical Advisor relationship with Actelion Please note: $20001 - $100000 by Irene Lang, source=Web Response, value=Grant/Research
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      Research support relationship with BMS Please note: $1-$1000 by Victor Tapson, source=Web Response, value=Grant/Research Support
      Research support relationship with EKOS Please note: $5001 - $20000 by Victor Tapson, source=Web Response, value=Grant/Research Support
      Research support relationship with Inari Please note: $5001 - $20000 by Victor Tapson, source=Web Response, value=Consulting fee
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      Consultant relationship with Arena Please note: $1001 - $5000 by Victor Tapson, source=Web Response, value=Consulting fee
      No relevant relationships by Carol Zhao, source=Web Response