Abstract
Background: Pulmonary arterial hypertension is a progressive, fatal disease. Published treatment guidelines recommend treatment escalation on the basis of regular patient assessment with the goal of achieving or maintaining low-risk status. Various strategies are available to determine risk status. This analysis describes an update of the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator (REVEAL 2.0) and compares it with recently published European Society of Cardiology/Respiratory Society guideline-derived risk assessment strategies. Methods: A subpopulation from the US-based registry REVEAL that survived ≥ 1 year postenrollment (baseline for this cohort) was analyzed. For REVEAL 2.0, point values and cutpoints were reassessed, and new variables were evaluated. The Kaplan-Meier method was used to estimate survival at 12 months postbaseline; discrimination was quantified using the c-statistic. Mortality estimates and discrimination were compared between REVEAL 2.0 and Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and French Pulmonary Hypertension Registry (FPHR) risk assessment strategies. For this comparison, a three-category REVEAL 2.0 score was computed in which patients were classified as low-, intermediate-, or high-risk. Results: REVEAL 2.0 demonstrated similar discrimination as the original calculator in this subpopulation (c-statistic = 0.76 vs 0.74), provided excellent separation of risk among the risk categories, and predicted clinical worsening as well as mortality in patients who were followed ≥ 1 year. The REVEAL 2.0 three-category score had greater discrimination (c-statistic = 0.73) than COMPERA (c-statistic = 0.62) or FPHR (c-statistic = 0.64). Compared with REVEAL 2.0, COMPERA and FPHR both underestimated and overestimated risk. Conclusions: REVEAL 2.0 demonstrates greater risk discrimination than the COMPERA and FPHR risk assessment strategies in patients enrolled in REVEAL. After external validation, the REVEAL 2.0 calculator can assist clinicians and patients in making informed treatment decisions on the basis of individual risk profiles. Trial Registry: ClinicalTrials.gov; No. NCT00370214; URL: www.clinicaltrials.gov.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 323-337 |
| Number of pages | 15 |
| Journal | Chest |
| Volume | 156 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2019 |
Keywords
- ESC/ERS-derived risk assessment
- REVEAL
- pulmonary arterial hypertension
- registry
- risk score calculator
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine
- Cardiology and Cardiovascular Medicine
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Predicting Survival in Patients With Pulmonary Arterial Hypertension : The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. / Benza, Raymond L.; Gomberg-Maitland, M.; Elliott, C. Greg; Farber, Harrison W.; Foreman, Aimee J.; Frost, Adaani E.; McGoon, Michael D.; Pasta, David J.; Selej, Mona; Burger, Charles D.; Frantz, Robert P.
In: Chest, Vol. 156, No. 2, 08.2019, p. 323-337.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Predicting Survival in Patients With Pulmonary Arterial Hypertension
T2 - The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies
AU - Benza, Raymond L.
AU - Gomberg-Maitland, M.
AU - Elliott, C. Greg
AU - Farber, Harrison W.
AU - Foreman, Aimee J.
AU - Frost, Adaani E.
AU - McGoon, Michael D.
AU - Pasta, David J.
AU - Selej, Mona
AU - Burger, Charles D.
AU - Frantz, Robert P.
N1 - Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: R. L. B. has received honoraria from Actelion Pharmaceuticals US, Inc., Gilead Sciences, Inc., and United Therapeutics Corporation; his institution received or is pending receipt of grants from Actelion , the American Heart Association , Bayer Corporation , the National Institutes of Health / National Heart, Lung, and Blood Institute (NIH/NHLBI), and United Therapeutics Corporation . M.G.-M. is a consultant to and a steering committee member/DSMB for Arena, Acceleron, Actelion Pharmaceuticals US, Inc., Bayer Corporation, Janssen, Liquidia, Medtronic, Inc., Merck, Reata, St. Jude’s, and United Therapeutics Corporation; her institution during development of the manuscript (Inova Heart and Vascular Institute) receives grant support from AADi, Actelion, and United Therapeutics for her to conduct clinical trials. C. G. E. is a consultant for Bellerophon Therapeutics, Inc., Actelion Pharmaceuticals US, Inc., and Bayer Corporation; he has received grant/research support from Actelion Pharmaceuticals US, Inc., Gilead Sciences , Inc., United Therapeutics Corporation , NIH / NHLBI , and Intermountain Research and Medical Foundation . H. W. F. has received grant/research support from Actelion Pharmaceuticals US, Inc., Gilead Sciences , Inc., and United Therapeutics Corporation ; is a member of the Speakers’ Bureau for Gilead Sciences, Inc., Bayer Corporation, and Actelion Pharmaceuticals US, Inc.; is an advisory board member for Bellerophon Therapeutics, Inc., Actelion Pharmaceuticals US, Inc., Bayer Corporation, Gilead Sciences, Inc., and United Therapeutics Corporation. A. J. F. and D. J. P. are former employees and former stockholders in ICON Clinical Research, which was paid by Actelion Pharmaceuticals US, Inc., to provide analytic services. A. E. F. is a consultant for Actelion Pharmaceuticals US, Inc., and Gilead Sciences, Inc., and received grant/research support for Bayer Corporation , Gilead Sciences , Inc., Actelion Pharmaceuticals US, Inc., Reata Pharmaceuticals, Complexa , Inc., and United Therapeutic Corporation . M. D. M. is on a data monitoring committee for Pfizer and Acceleron and on an advisory committee for Lung Biotechnology. M. S. is an employee of and stockholder in Actelion Pharmaceuticals US, Inc. (a Janssen Pharmaceutical Company of Johnson and Johnson). C. D. B. served as an advisory board member for Actelion Pharmaceuticals US, Inc., and Gilead Sciences, Inc., and received grant/research support for Gilead Sciences, Inc., Actelion Pharmaceuticals US, Inc., and United Therapeutics Corporation. R. P. F. is a consultant and steering committee member for Actelion Pharmaceuticals US, Inc., United Therapeutics Corporation, and St. Jude Medical, Inc.; is a consultant for Arena and Bayer Pharmaceuticals. Third-party medical editorial assistance was provided by Twist Medical and by Donna Simcoe of Simcoe Consultants, Inc., which were supported by Actelion Pharmaceuticals US, Inc. Funding Information: Author contributions: R. L. B. takes responsibility for the content of the manuscript, including the data and analysis. R. L. B. M. G.-M. C. G. E. H. W. F. A. J. F. A. E. F. M. D. M. D. J. P. M. S. C. D. B. and R. P. F. were involved in study concept and design, preparation of the draft manuscript, and critical revision and approval of the final manuscript for interpretation of the data and important intellectual input. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: R. L. B. has received honoraria from Actelion Pharmaceuticals US, Inc. Gilead Sciences, Inc. and United Therapeutics Corporation; his institution received or is pending receipt of grants from Actelion, the American Heart Association, Bayer Corporation, the National Institutes of Health/ National Heart, Lung, and Blood Institute (NIH/NHLBI), and United Therapeutics Corporation. M.G.-M. is a consultant to and a steering committee member/DSMB for Arena, Acceleron, Actelion Pharmaceuticals US, Inc. Bayer Corporation, Janssen, Liquidia, Medtronic, Inc. Merck, Reata, St. Jude's, and United Therapeutics Corporation; her institution during development of the manuscript (Inova Heart and Vascular Institute) receives grant support from AADi, Actelion, and United Therapeutics for her to conduct clinical trials. C. G. E. is a consultant for Bellerophon Therapeutics, Inc. Actelion Pharmaceuticals US, Inc. and Bayer Corporation; he has received grant/research support from Actelion Pharmaceuticals US, Inc. Gilead Sciences, Inc. United Therapeutics Corporation, NIH/NHLBI, and Intermountain Research and Medical Foundation. H. W. F. has received grant/research support from Actelion Pharmaceuticals US, Inc. Gilead Sciences, Inc. and United Therapeutics Corporation; is a member of the Speakers’ Bureau for Gilead Sciences, Inc. Bayer Corporation, and Actelion Pharmaceuticals US, Inc.; is an advisory board member for Bellerophon Therapeutics, Inc. Actelion Pharmaceuticals US, Inc. Bayer Corporation, Gilead Sciences, Inc. and United Therapeutics Corporation. A. J. F. and D. J. P. are former employees and former stockholders in ICON Clinical Research, which was paid by Actelion Pharmaceuticals US, Inc. to provide analytic services. A. E. F. is a consultant for Actelion Pharmaceuticals US, Inc. and Gilead Sciences, Inc. and received grant/research support for Bayer Corporation, Gilead Sciences, Inc. Actelion Pharmaceuticals US, Inc. Reata Pharmaceuticals, Complexa, Inc. and United Therapeutic Corporation. M. D. M. is on a data monitoring committee for Pfizer and Acceleron and on an advisory committee for Lung Biotechnology. M. S. is an employee of and stockholder in Actelion Pharmaceuticals US, Inc. (a Janssen Pharmaceutical Company of Johnson and Johnson). C. D. B. served as an advisory board member for Actelion Pharmaceuticals US, Inc. and Gilead Sciences, Inc. and received grant/research support for Gilead Sciences, Inc. Actelion Pharmaceuticals US, Inc. and United Therapeutics Corporation. R. P. F. is a consultant and steering committee member for Actelion Pharmaceuticals US, Inc. United Therapeutics Corporation, and St. Jude Medical, Inc.; is a consultant for Arena and Bayer Pharmaceuticals. Third-party medical editorial assistance was provided by Twist Medical and by Donna Simcoe of Simcoe Consultants, Inc. which were supported by Actelion Pharmaceuticals US, Inc. Role of the sponsor: The sponsor had no role in the design of the study, or the collection and analysis of the data. One of the authors (Dr Selej) is an employee of the sponsor and participated to a similar degree as the other authors in the preparation of the manuscript. Additional information: The e-Appendix can be found in the Supplemental Materials section of the online article. Funding Information: Author contributions: R. L. B. takes responsibility for the content of the manuscript, including the data and analysis. R. L. B. M. G.-M. C. G. E. H. W. F. A. J. F. A. E. F. M. D. M. D. J. P. M. S. C. D. B. and R. P. F. were involved in study concept and design, preparation of the draft manuscript, and critical revision and approval of the final manuscript for interpretation of the data and important intellectual input. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: R. L. B. has received honoraria from Actelion Pharmaceuticals US, Inc. Gilead Sciences, Inc. and United Therapeutics Corporation; his institution received or is pending receipt of grants from Actelion, the American Heart Association, Bayer Corporation, the National Institutes of Health/ National Heart, Lung, and Blood Institute (NIH/NHLBI), and United Therapeutics Corporation. M.G.-M. is a consultant to and a steering committee member/DSMB for Arena, Acceleron, Actelion Pharmaceuticals US, Inc. Bayer Corporation, Janssen, Liquidia, Medtronic, Inc. Merck, Reata, St. Jude's, and United Therapeutics Corporation; her institution during development of the manuscript (Inova Heart and Vascular Institute) receives grant support from AADi, Actelion, and United Therapeutics for her to conduct clinical trials. C. G. E. is a consultant for Bellerophon Therapeutics, Inc. Actelion Pharmaceuticals US, Inc. and Bayer Corporation; he has received grant/research support from Actelion Pharmaceuticals US, Inc. Gilead Sciences, Inc. United Therapeutics Corporation, NIH/NHLBI, and Intermountain Research and Medical Foundation. H. W. F. has received grant/research support from Actelion Pharmaceuticals US, Inc. Gilead Sciences, Inc. and United Therapeutics Corporation; is a member of the Speakers’ Bureau for Gilead Sciences, Inc. Bayer Corporation, and Actelion Pharmaceuticals US, Inc.; is an advisory board member for Bellerophon Therapeutics, Inc. Actelion Pharmaceuticals US, Inc. Bayer Corporation, Gilead Sciences, Inc. and United Therapeutics Corporation. A. J. F. and D. J. P. are former employees and former stockholders in ICON Clinical Research, which was paid by Actelion Pharmaceuticals US, Inc. to provide analytic services. A. E. F. is a consultant for Actelion Pharmaceuticals US, Inc. and Gilead Sciences, Inc. and received grant/research support for Bayer Corporation, Gilead Sciences, Inc. Actelion Pharmaceuticals US, Inc. Reata Pharmaceuticals, Complexa, Inc. and United Therapeutic Corporation. M. D. M. is on a data monitoring committee for Pfizer and Acceleron and on an advisory committee for Lung Biotechnology. M. S. is an employee of and stockholder in Actelion Pharmaceuticals US, Inc. (a Janssen Pharmaceutical Company of Johnson and Johnson). C. D. B. served as an advisory board member for Actelion Pharmaceuticals US, Inc. and Gilead Sciences, Inc. and received grant/research support for Gilead Sciences, Inc. Actelion Pharmaceuticals US, Inc. and United Therapeutics Corporation. R. P. F. is a consultant and steering committee member for Actelion Pharmaceuticals US, Inc. United Therapeutics Corporation, and St. Jude Medical, Inc.; is a consultant for Arena and Bayer Pharmaceuticals. Third-party medical editorial assistance was provided by Twist Medical and by Donna Simcoe of Simcoe Consultants, Inc. which were supported by Actelion Pharmaceuticals US, Inc. Role of the sponsor: The sponsor had no role in the design of the study, or the collection and analysis of the data. One of the authors (Dr Selej) is an employee of the sponsor and participated to a similar degree as the other authors in the preparation of the manuscript. Additional information: The e-Appendix can be found in the Supplemental Materials section of the online article. FUNDING/SUPPORT: Actelion Pharmaceuticals US, Inc. (A Janssen Pharmaceutical Company of Johnson and Johnson) is the sponsor of the Registry to Evaluate Early and Long-Term PAH Disease Management Registry and provided funding and support for the analysis presented. Publisher Copyright: © 2019 The Authors
PY - 2019/8
Y1 - 2019/8
N2 - Background: Pulmonary arterial hypertension is a progressive, fatal disease. Published treatment guidelines recommend treatment escalation on the basis of regular patient assessment with the goal of achieving or maintaining low-risk status. Various strategies are available to determine risk status. This analysis describes an update of the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator (REVEAL 2.0) and compares it with recently published European Society of Cardiology/Respiratory Society guideline-derived risk assessment strategies. Methods: A subpopulation from the US-based registry REVEAL that survived ≥ 1 year postenrollment (baseline for this cohort) was analyzed. For REVEAL 2.0, point values and cutpoints were reassessed, and new variables were evaluated. The Kaplan-Meier method was used to estimate survival at 12 months postbaseline; discrimination was quantified using the c-statistic. Mortality estimates and discrimination were compared between REVEAL 2.0 and Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and French Pulmonary Hypertension Registry (FPHR) risk assessment strategies. For this comparison, a three-category REVEAL 2.0 score was computed in which patients were classified as low-, intermediate-, or high-risk. Results: REVEAL 2.0 demonstrated similar discrimination as the original calculator in this subpopulation (c-statistic = 0.76 vs 0.74), provided excellent separation of risk among the risk categories, and predicted clinical worsening as well as mortality in patients who were followed ≥ 1 year. The REVEAL 2.0 three-category score had greater discrimination (c-statistic = 0.73) than COMPERA (c-statistic = 0.62) or FPHR (c-statistic = 0.64). Compared with REVEAL 2.0, COMPERA and FPHR both underestimated and overestimated risk. Conclusions: REVEAL 2.0 demonstrates greater risk discrimination than the COMPERA and FPHR risk assessment strategies in patients enrolled in REVEAL. After external validation, the REVEAL 2.0 calculator can assist clinicians and patients in making informed treatment decisions on the basis of individual risk profiles. Trial Registry: ClinicalTrials.gov; No. NCT00370214; URL: www.clinicaltrials.gov.
AB - Background: Pulmonary arterial hypertension is a progressive, fatal disease. Published treatment guidelines recommend treatment escalation on the basis of regular patient assessment with the goal of achieving or maintaining low-risk status. Various strategies are available to determine risk status. This analysis describes an update of the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator (REVEAL 2.0) and compares it with recently published European Society of Cardiology/Respiratory Society guideline-derived risk assessment strategies. Methods: A subpopulation from the US-based registry REVEAL that survived ≥ 1 year postenrollment (baseline for this cohort) was analyzed. For REVEAL 2.0, point values and cutpoints were reassessed, and new variables were evaluated. The Kaplan-Meier method was used to estimate survival at 12 months postbaseline; discrimination was quantified using the c-statistic. Mortality estimates and discrimination were compared between REVEAL 2.0 and Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and French Pulmonary Hypertension Registry (FPHR) risk assessment strategies. For this comparison, a three-category REVEAL 2.0 score was computed in which patients were classified as low-, intermediate-, or high-risk. Results: REVEAL 2.0 demonstrated similar discrimination as the original calculator in this subpopulation (c-statistic = 0.76 vs 0.74), provided excellent separation of risk among the risk categories, and predicted clinical worsening as well as mortality in patients who were followed ≥ 1 year. The REVEAL 2.0 three-category score had greater discrimination (c-statistic = 0.73) than COMPERA (c-statistic = 0.62) or FPHR (c-statistic = 0.64). Compared with REVEAL 2.0, COMPERA and FPHR both underestimated and overestimated risk. Conclusions: REVEAL 2.0 demonstrates greater risk discrimination than the COMPERA and FPHR risk assessment strategies in patients enrolled in REVEAL. After external validation, the REVEAL 2.0 calculator can assist clinicians and patients in making informed treatment decisions on the basis of individual risk profiles. Trial Registry: ClinicalTrials.gov; No. NCT00370214; URL: www.clinicaltrials.gov.
KW - ESC/ERS-derived risk assessment
KW - REVEAL
KW - pulmonary arterial hypertension
KW - registry
KW - risk score calculator
UR - http://www.scopus.com/inward/record.url?scp=85064328696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064328696&partnerID=8YFLogxK
U2 - 10.1016/j.chest.2019.02.004
DO - 10.1016/j.chest.2019.02.004
M3 - Article
C2 - 30772387
AN - SCOPUS:85064328696
VL - 156
SP - 323
EP - 337
JO - Diseases of the chest
JF - Diseases of the chest
SN - 0012-3692
IS - 2
ER -