TY - JOUR
T1 - Improved risk stratification of patients with atrial fibrillation
T2 - An integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation
AU - GARFIELD-AF Investigators
AU - Fox, Keith A.A.
AU - Lucas, Joseph E.
AU - Pieper, Karen S.
AU - Bassand, Jean Pierre
AU - Camm, A. John
AU - Fitzmaurice, David A.
AU - Goldhaber, Samuel Z.
AU - Goto, Shinya
AU - Haas, Sylvia
AU - Hacke, Werner
AU - Kayani, Gloria
AU - Oto, Ali
AU - Mantovani, Lorenzo G.
AU - Misselwitz, Frank
AU - Piccini, Jonathan P.
AU - Turpie, Alexander G.G.
AU - Verheugt, Freek W.A.
AU - Kakkar, Ajay K.
AU - van Eickels, Martin
AU - Gersh, Bernard J.
AU - Luciardi, Hector Lucas
AU - Gibbs, Harry
AU - Brodmann, Marianne
AU - Cools, Frank
AU - Barretto, Antonio Carlos Pereira
AU - Connolly, Stuart J.
AU - Spyropoulos, Alex
AU - Eikelboom, John
AU - Corbalan, Ramon
AU - Hu, Dayi
AU - Jansky, Petr
AU - Nielsen, Jørn Dalsgaard
AU - Ragy, Hany
AU - Raatikainen, Pekka
AU - Le Heuzey, Jean Yves
AU - Darius, Harald
AU - Keltai, Matyas
AU - Kakkar, Sanjay
AU - Sawhney, Jitendra Pal Singh
AU - Agnelli, Giancarlo
AU - Ambrosio, Giuseppe
AU - Koretsune, Yukihiro
AU - Díaz, Carlos Jerjes Sánchez
AU - ten Cate, Hugo
AU - Atar, Dan
AU - Stepinska, Janina
AU - Panchenko, Elizaveta
AU - Lim, Toon Wei
AU - Lim, H. E.
AU - Shim, J.
N1 - Funding Information:
1Edinburgh Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK 2Department of Statistical Science, Duke University, Durham, North Carolina, USA 3Department of Statistical Research Science, Duke Clinical Research Institute, Durham, North Carolina, USA 4Department of Cardiology, University of Besançon, Besançon, France 5Department of Clinical Research, Thrombosis Research Institute (TRI), London, UK 6Department of Clinical Cardiology, St George's University London, London, UK 7Department of Cardio-respiratory Primary Care, Warwick Medical School, University of Warwick, Coventry, UK 8Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA 9Department of Medicine, Tokai University, Kanagawa, Japan 10Department of Medicine, Formerly Technical University Of Munich, Munich, Germany 11Department of Neurology, University of Heidelberg, Heidelberg, Germany 12Department of Cardiology, Hacettepe University, Ankara, Turkey 13Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy 14Department of Cardiovascular & Coagulation, Bayer AG, Berlin, Germany 15Department of Medicine, McMaster University, Hamilton, Canada 16Department of Cardiology, University Hospital, Nijmegen, The Netherlands 17Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands 18Department of Surgery, University College London, London, UK Acknowledgements We would like to thank the physicians, nurses and patients involved in the GARFIELD-AF registry. Editorial support was provided by Rae Hobbs (TRI, London, UK) and SAS programming support by Jagan Allu (TRI, London, UK).
Funding Information:
Funding This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the GARFIELD-AF registry.
Funding Information:
Competing interests KAAF reports grants and personal fees from Bayer, and Johnson and Johnson, personal fees from Lilly, grants and personal fees from AstraZeneca and personal fees from Sanofi/Regeneron outside the submitted work. JEL and KSP have provided statistical support and thought leadership for the Thrombosis Research Institute, during the conduct of the study, and KSP has received personal fees from Bayer outside the submitted work. J-PB reports personal fees from Aspen outside the submitted work. AJC is an advisor to Bayer, Boehringer Ingelheim, Pfizer/BMS and Daiichi Sankyo. DAF reports personal fees from Bayer outside the submitted work. SZG reports grants from BiO2 Medical, Boehringer-Ingelheim, Bristol Meyers Squibb, BTG EKOS, Daiichi Sankyo, National Heart Lung and Blood Institute of the National Institutes of Health, Janssen and Thrombosis Research Group and personal fees from Bayer, Boehringer-Ingelheim, Bristol Meyers Squibb, Daiichi Sankyo, Janssen and Portola outside the submitted work. SG reports personal fees from Bayer, grants from Sanofi, grants from Pfizer, personal fees from Daiichi-Sankyo, personal fees from AstraZeneca during the conduct of the study and grants from Bayer outside the submitted work. SH reports personal fees from Aspen, Bayer AG, BMS, Daiichi-Sankyo, Pfizer and Sanofi outside the submitted work. WH reports personal fees from Bayer during the conduct of the study. GK reports grants from Bayer during the conduct of the study. LGM reports grants and personal fees from Bayer AG during the conduct of the study, and grants from Boehringer Ingelheim, grants and personal fees from Pfizer and personal fees from Daiichi Sankyo outside the submitted work. FM reports grants and other from Bayer AG during the conduct of the study, and other from Bayer AG outside the submitted work. FM is an employee of Bayer AG. JP has nothing to disclose. AGGT reports consultant fees from Bayer AG during the conduct of the study. FWAV reports personal fees from Boehringer-Ingelheim, Bayer AG, BMS/Pfizer and Daiichi-Sankyo during the conduct of the study and personal fees from AstraZeneca outside the submitted work. AKK reports grants and personal fees from Bayer AG, Boehringer-Ingelheim Pharma, Daiichi Sankyo Europe, Sanofi SA and Janssen Pharma outside the submitted work.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Objectives: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. Design: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2 DS2 -VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Participants: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. Results: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2 DS2 -VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2 DS2 -VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2 DS2 -VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2 DS2 -VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2 DS2 -VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). Conclusions: Performance of the GARFIELD-AF risk tool was superior to CHA2 DS2 -VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks.
AB - Objectives: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. Design: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2 DS2 -VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Participants: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. Results: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2 DS2 -VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2 DS2 -VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2 DS2 -VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2 DS2 -VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2 DS2 -VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). Conclusions: Performance of the GARFIELD-AF risk tool was superior to CHA2 DS2 -VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks.
KW - CHA DS -VASc
KW - atrial fibrillation
KW - risk stratification
UR - http://www.scopus.com/inward/record.url?scp=85050124792&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050124792&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2017-017157
DO - 10.1136/bmjopen-2017-017157
M3 - Article
C2 - 29273652
AN - SCOPUS:85050124792
VL - 7
JO - BMJ Open
JF - BMJ Open
SN - 2044-6055
IS - 12
M1 - e017157
ER -