Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis

被引：19

作者：

Hoeper, Marius M. ^{[1
,2
]}

Pausch, Christine ^{[3
]}

Olsson, Karen M. ^{[1
,2
]}

Huscher, Doerte ^{[4
]}

Pittrow, David ^{[3
,5
]}

Gruenig, Ekkehard ^{[6
]}

Staehler, Gerd ^{[7
]}

Vizza, Carmine Dario ^{[8
]}

Gall, Henning ^{[2
,9
]}

Distler, Oliver ^{[10
]}

Opitz, Christian ^{[11
]}

Gibbs, J. Simon R. ^{[12
]}

Delcroix, Marion ^{[13
,14
]}

Ghofrani, H. Ardeschir ^{[2
,9
,15
]}

Ewert, Ralf ^{[16
]}

Kaemmerer, Harald ^{[17
]}

Kabitz, Hans-Joachim ^{[18
]}

Skowasch, Dirk ^{[19
]}

Behr, Juergen ^{[20
,21
,22
]}

Milger, Katrin ^{[21
,22
]}

Halank, Michael ^{[23
]}

Wilkens, Heinrike ^{[24
]}

Seyfarth, Hans-Juergen ^{[25
]}

Held, Matthias ^{[26
]}

Dumitrescu, Daniel ^{[27
]}

Tsangaris, Iraklis ^{[28
]}

Vonk-Noordegraaf, Anton ^{[29
]}

Ulrich, Silvia ^{[30
]}

Klose, Hans ^{[31
]}

Claussen, Martin ^{[32
]}

Eisenmann, Stephan ^{[33
]}

Schmidt, Kai-Helge ^{[34
,35
]}

Rosenkranz, Stephan ^{[36
,37
,38
]}

Lange, Tobias J. ^{[39
]}

机构：

[1] Hannover Med Sch, Dept Resp Med, D-30623 Hannover, Germany

[2] German Ctr Lung Res DZL, Giessen, Germany

[3] GWT TUD GmbH, Epidemiol Ctr, Dresden, Germany

[4] Charite, Inst Biometry & Clin Epidemiol, Berlin, Germany

[5] Tech Univ, Inst Clin Pharmacol, Med Fac, Dresden, Germany

[6] Heidelberg Univ Hosp, Ctr Pulm Hypertens, Translat Lung Res Ctr Heidelberg TLRC, German Ctr Lung Res DZL,Thoraxklin, Heidelberg, Germany

[7] Lungenklinik, Lowenstein, Germany

[8] Sapienza Univ Rome, Dipartimento Sci Clin Internist Anestiol & Cardio, Rome, Italy

[9] Justus Liebig Univ Giessen, Univ Giessen & Marburg Lung Ctr UGMLC, Dept Internal Med, Giessen, Germany

[10] Univ Hosp, Dept Rheumatol, Zurich, Switzerland

[11] DRK Kliniken Berlin Westend, Dept Cardiol, Berlin, Germany

[12] Imperial Coll London, Natl Heart & Lung Inst, Dept Cardiol, London, England

[13] Univ Hosp Leuven, Clin Dept Resp Dis, Leuven, Belgium

[14] KU Leuven Univ Leuven, Lab Resp Dis & Thorac Surg BREATHE, Dept Chron Dis & Metab CHROMETA, Leuven, Belgium

[15] Imperial Coll London, Dept Med, London, England

[16] Univ Med Greifswald, Dept Resp Med, Clin Internal Med, Greifswald, Germany

[17] Tech Univ Munich, Klin Angeborene Herzfehler & Kinderkardiol, Deutsch Herzzentrum Munchen, Munich, Germany

[18] Gemeinnutzige Krankenhausbetriebsgesellschaft Kon, Med Klin 2, Constance, Germany

[19] Univ Klinikum Bonn, Med Klin & Poliklin 2, Innere Med Kardiol Pneumol, Bonn, Germany

[20] Helmholtz Zentrum, Comprehens Pneumol Ctr, Lungenforsch Ambulanz, Munich, Germany

[21] Ludwig Maximilians Univ Munchen, Comprehens Pneumol Ctr Munich CPC M, Univ Hosp, Dept Med 5, Munich, Germany

[22] German Ctr Lung Res DZL, Munich, Germany

[23] Techn Univ Dresden, Med Klin & Poliklin 1, Univ Klinikum Carl Gustav Carus, Dresden, Germany

[24] Univ Klinikum Univ Klinikum Saarlandes, Klin Innere Med 5, Pneumol, Homburg, Germany

[25] Univ Klinikum Leipzig, Med Klin & Poliklin 2, Abt Pneumol, Leipzig, Germany

[26] Med Miss Hosp, Cent Clin Wurzburg, Dept Internal Med Resp Med & Ventilatory Support, Wurzburg, Germany

[27] Ruhr Univ Bochum, Herz & Diabeteszentrum NRW, Clin Gen & Intervent Cardiol & Angiol, Bad Oeynhausen, Germany

[28] Natl & Kapodistrian Univ Athens, Attikon Univ Hosp, Crit Care Dept 2, Athens, Greece

[29] Vrije Univ Amsterdam, Dept Pulm Med, Amsterdam Cardiovasc Sci, Amsterdam UMC, Amsterdam, Netherlands

[30] Univ Hosp Zurich, Clin Pulmonol, Zurich, Switzerland

[31] Eppendorf Univ Hosp, Dept Resp Med, Hamburg, Germany

[32] LungenClin Grosshansdorf, Fachabt Pneumol, Grohansdorf, Germany

[33] Univ Klinikum Halle, Dept Resp Med, Halle, Germany

[34] Univ Med Ctr Mainz, Dept Cardiol, Mainz, Germany

[35] Univ Med Ctr Mainz, Ctr Thrombosis & Hemostasis CTH, Mainz, Germany

[36] Univ Cologne, Clin Internal Med Cardiol 3, Cologne, Germany

[37] Univ Cologne, Ctr Mol Med CMMC, Cologne, Germany

[38] Univ Cologne, Cologne Cardiovasc Res Ctr CCRC, Cologne, Germany

[39] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany

来源：

JOURNAL OF HEART AND LUNG TRANSPLANTATION | 2022年 / 41卷 / 07期

关键词：

pulmonary arterial hypertension; treatment; clinical trials; endpoints; risk; mortality; WALK DISTANCE; RISK SCORE; THERAPY; AMBRISENTAN; MORBIDITY; TADALAFIL; RIOCIGUAT; MORTALITY; SURVIVAL; BOSENTAN;

D O I：

10.1016/j.healun.2022.03.011

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND: The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated. METHODS: Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses. RESULTS: All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by >= 35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools. CONCLUSION: While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials. (C) 2022 The Author(s). Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.

引用

页码：971 / 981

页数：11

共 38 条

[1] Functional Class Improvement and 3-Year Survival Outcomes in Patients With Pulmonary Arterial Hypertension in the REVEAL Registry [J].

Barst, Robyn J. ;

Chung, Lorinda ;

Zamanian, Roham T. ;

Turner, Michelle ;

McGoon, Michael D. .

CHEST, 2013, 144 (01) :160-168

[2] Development and Validation of an Abridged Version of the REVEAL 2.0 Risk Score Calculator, REVEAL Lite 2, for Use in Patients With Pulmonary Arterial Hypertension [J].

Benza, Raymond L. ;

Kanwar, Manreet K. ;

Raina, Amresh ;

Scott, Jacqueline V. ;

Zhao, Carol L. ;

Selej, Mona ;

Elliott, C. Greg ;

Farber, Harrison W. .

CHEST, 2021, 159 (01) :337-346

[3] Predicting Survival in Patients With Pulmonary Arterial Hypertension The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies [J].

Benza, Raymond L. ;

Gomberg-Maitland, Mardi ;

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. .

CHEST, 2019, 156 (02) :323-337

[4] REVEAL risk scores applied to riociguat-treated patients in PATENT-2: Impact of changes in risk score on survival [J].

Benza, Raymond L. ;

Farber, Harrison W. ;

Frost, Adaani ;

Ghofrani, Hossein-Ardeschir ;

Gomez-Sanchez, Miguel A. ;

Langleben, David ;

Rosenkranz, Stephan ;

Busse, Dennis ;

Meier, Christian ;

Nikkho, Sylvia ;

Hoeper, Marius M. .

JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2018, 37 (04) :513-519

[5] External validation of a refined four-stratum risk assessment score from the French pulmonary hypertension registry [J].

Boucly, Athenais ;

Weatherald, Jason ;

Savale, Laurent ;

de Groote, Pascal ;

Cottin, Vincent ;

Prevot, Gregoire ;

Chaouat, Ari ;

Picard, Francois ;

Horeau-Langlard, Delphine ;

Bourdin, Arnaud ;

Jutant, Etienne-Marie ;

Beurnier, Antoine ;

Jevnikar, Mitja ;

Jais, Xavier ;

Simonneau, Gerald ;

Montani, David ;

Sitbon, Olivier ;

Humbert, Marc .

EUROPEAN RESPIRATORY JOURNAL, 2022, 59 (06)

[6] Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension [J].

Boucly, Athenais ;

Weatherald, Jason ;

Savale, Laurent ;

Jais, Xavier ;

Cottin, Vincent ;

Prevot, Gregoire ;

Picard, Francois ;

de Groote, Pascal ;

Jevnikar, Mitja ;

Bergot, Emmanuel ;

Chaouat, Ari ;

Chabanne, Celine ;

Bourdin, Arnaud ;

Parent, Florence ;

Montani, David ;

Simonneau, Gerald ;

Humbert, Marc ;

Sitbon, Olivier .

EUROPEAN RESPIRATORY JOURNAL, 2017, 50 (02)

[7] Landmark Analysis at the 25-Year Landmark Point [J].

Dafni, Urania .

CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES, 2011, 4 (03) :363-U216

[8] Biomarkers and surrogate endpoints in clinical trials [J].

Fleming, Thomas R. ;

Powers, John H. .

STATISTICS IN MEDICINE, 2012, 31 (25) :2973-2984

[9] Baseline and Follow-up 6-Min Walk Distance and Brain Natriuretic Peptide Predict 2-Year Mortality in Pulmonary Arterial Hypertension [J].

Fritz, Jason S. ;

Blair, Christiana ;

Oudiz, Ronald J. ;

Dufton, Christopher ;

Olschewski, Horst ;

Despain, Darrin ;

Gillies, Hunter ;

Kawut, Steven M. .

CHEST, 2013, 143 (02) :315-323

[10] Race and Sex Differences in Response to Endothelin Receptor Antagonists for Pulmonary Arterial Hypertension [J].

Gabler, Nicole B. ;

French, Benjamin ;

Strom, Brian L. ;

Liu, Ziyue ;

Palevsky, Harold I. ;

Taichman, Darren B. ;

Kawut, Steven M. ;

Halpern, Scott D. .

CHEST, 2012, 141 (01) :20-26

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