PMID- 37596725
OWN - NLM
STAT- MEDLINE
DCOM- 20231114
LR  - 20231115
IS  - 1932-8737 (Electronic)
IS  - 0160-9289 (Print)
IS  - 0160-9289 (Linking)
VI  - 46
IP  - 11
DP  - 2023 Nov
TI  - Predictors of intracranial hemorrhage in patients with atrial fibrillation 
      treated with oral anticoagulants: Insights from the GARFIELD-AF and ORBIT-AF 
      registries.
PG  - 1398-1407
LID - 10.1002/clc.24109 [doi]
AB  - BACKGROUND: An unmet need exists to reliably predict the risk of intracranial 
      hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral 
      anticoagulants (OACs). HYPOTHESIS: An externally validated model improves ICH 
      risk stratification. METHODS: Independent factors associated with ICH were 
      identified by Cox proportional hazard modeling, using pooled data from the 
      GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and 
      ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) 
      registries. A predictive model was developed and validated by bootstrap sampling 
      and by independent data from the Danish National Patient Register. RESULTS: In 
      the combined training data set, 284 of 53 878 anticoagulated patients had ICH 
      over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 
      0.28-0.35). Independent predictors of ICH included: older age, prior stroke or 
      transient ischemic attack, concomitant antiplatelet (AP) use, and 
      moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) 
      were associated with a significantly higher risk of ICH compared with non-VKA 
      oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; 
      p = .0002). The ability of the model to discriminate individuals in the training 
      set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 
      0.65-0.71) and outperformed three previously published methods. Calibration 
      between predicted and observed ICH probabilities was good in both training and 
      validation data sets. CONCLUSIONS: Age, prior ischemic events, concomitant AP 
      therapy, and CKD were important risk factors for ICH in anticoagulated AF 
      patients. Moreover, ICH was more frequent in patients receiving VKA compared to 
      NOAC. The new validated model is a step toward mitigating this potentially lethal 
      complication.
CI  - (c) 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.
FAU - Lim, Toon Wei
AU  - Lim TW
AUID- ORCID: 0000-0002-3429-9237
AD  - National Heart Centre, Singapore, Singapore.
AD  - National University Hospital, Singapore, Singapore.
FAU - Camm, Alan John
AU  - Camm AJ
AUID- ORCID: 0000-0002-2536-2871
AD  - Cardiology Clinical Academic Group Molecular & Clinical Sciences Institute, St. 
      George's University of London, London, UK.
FAU - Virdone, Saverio
AU  - Virdone S
AD  - Thrombosis Research Institute, London, UK.
FAU - Singer, Daniel E
AU  - Singer DE
AD  - Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 
      USA.
FAU - Bassand, Jean P
AU  - Bassand JP
AD  - Thrombosis Research Institute, London, UK.
AD  - Department of Cardiology, University of Besancon, Besancon, France.
FAU - Fonarow, Gregg C
AU  - Fonarow GC
AUID- ORCID: 0000-0002-3192-8093
AD  - Ronald Reagan-UCLA Medical Center, Los Angeles, California, USA.
FAU - Fox, Keith A A
AU  - Fox KAA
AD  - Department of Cardiovascular Science, Centre for Cardiovascular Science, 
      University of Edinburgh, Edinburgh, UK.
FAU - Ezekowitz, Michael
AU  - Ezekowitz M
AD  - Sidney Kimmel Medical School, Thomas Jefferson University, Philadelphia, 
      Pennsylvania, USA.
FAU - Gersh, Bernard J
AU  - Gersh BJ
AD  - Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA.
FAU - Kayani, Gloria
AU  - Kayani G
AD  - Thrombosis Research Institute, London, UK.
FAU - Hylek, Elaine M
AU  - Hylek EM
AD  - Department of Medicine, Boston University School of Medicine, Boston, 
      Massachusetts, USA.
FAU - Kakkar, Ajay K
AU  - Kakkar AK
AD  - Thrombosis Research Institute, London, UK.
AD  - Department of Surgery, University College London, London, UK.
FAU - Mahaffey, Kenneth W
AU  - Mahaffey KW
AD  - Stanford Center for Clinical Research, Stanford School of Medicine, Stanford, 
      California, USA.
FAU - Pieper, Karen S
AU  - Pieper KS
AD  - Thrombosis Research Institute, London, UK.
AD  - Department of Cardiac Electrophysiology, Duke Clinical Research Institute, 
      Durham, North Carolina, USA.
FAU - Peterson, Eric D
AU  - Peterson ED
AD  - Department of Cardiac Electrophysiology, Duke Clinical Research Institute, 
      Durham, North Carolina, USA.
AD  - Duke University School of Medicine, Durham, North Carolina, USA.
FAU - Piccini, Jonathan P
AU  - Piccini JP
AUID- ORCID: 0000-0003-0772-2404
AD  - Department of Cardiac Electrophysiology, Duke Clinical Research Institute, 
      Durham, North Carolina, USA.
AD  - Duke University School of Medicine, Durham, North Carolina, USA.
CN  - GARFIELD-AF and ORBIT-AF Investigators
LA  - eng
GR  - Thrombosis Research Institute/
GR  - Janssen Scientific Affairs LLC/
PT  - Journal Article
DEP - 20230818
PL  - United States
TA  - Clin Cardiol
JT  - Clinical cardiology
JID - 7903272
RN  - 0 (Anticoagulants)
RN  - 12001-79-5 (Vitamin K)
SB  - IM
MH  - Humans
MH  - Anticoagulants
MH  - *Atrial Fibrillation/complications/diagnosis/drug therapy
MH  - Administration, Oral
MH  - Intracranial Hemorrhages/chemically induced/diagnosis/epidemiology
MH  - *Stroke/etiology
MH  - Risk Factors
MH  - Registries
MH  - *Renal Insufficiency, Chronic/complications
MH  - Vitamin K
PMC - PMC10642328
OTO - NOTNLM
OT  - anticoagulation
OT  - atrial fibrillation (AF)
OT  - chronic kidney disease
OT  - intracranial hemorrhage (ICH)
OT  - nonvitamin K antagonist (NOAC)
OT  - oral anticoagulant (OAC)
OT  - real-world evidence (RWE)
OT  - risk prediction
OT  - vitamin K antagonist (VKA)
COIS- Toon Wei Lim has received research support from Bayer, Boehringer Ingelheim, and 
      Pfizer. Alan John Camm has received institutional grants and personal fees from 
      Bayer, Boehringer Ingelheim, Pfizer/BMS, and Daiichi Sankyo and personal fees 
      from Portola. Daniel E. Singer has received research grants from Boehringer 
      Ingelheim and Bristol-Myers Squibb and consulting fees from Boehringer Ingelheim, 
      Bristol-Myers Squibb, Johnson & Johnson, Merck, and Pfizer. Jean-Pierre Bassand 
      reports personal fees from Thrombosis Research Institute. Gregg C. Fonarow has 
      consulted for Abbott, Bayer, Janssen, Medtronic, and Novartis. Keith A.A. Fox has 
      received grants and personal fees from Sanofi, Bayer, and Anthos. Michael 
      Ezekowitz has consulted for Boehringer Ingelheim, Daiichi Sankyo, Bristol-Myers 
      Squibb, and Janssen Scientific Affairs. Bernard J. Gersh is a member of Data 
      Safety Monitoring Board-Mount Sinai St. Luke's, Boston Scientific Corporation, 
      Teva Pharmaceutical Industries, St. Jude Medical, Janssen Research & Development, 
      TRI, Duke Clinical Research Institute, Duke University, Kowa Research Institute, 
      Cardiovascular Research Foundation, and Medtronic and consults for Janssen 
      Scientific Affairs, Xenon Pharmaceuticals, and Sirtex Medical. Elaine M. Hylek 
      consults for Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Janssen, 
      Medtronic, and Pfizer. Ajay K. Kakkar has received research support from Bayer AG 
      and Sanofi; personal fees from Bayer AG, Janssen Pharma, Pfizer, Sanofi, Verseon, 
      and Anthos Therapeutics. Kenneth W. Mahaffey has received research support from 
      Afferent, Amgen, Apple, AstraZeneca, Cardiva Medical, Daiichi Sankyo, Ferring, 
      Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, 
      Sanofi, St. Jude, and Tenax, and reports consulting or other services for Abbott, 
      Ablynx, AstraZeneca, Baim Institute, Boehringer Ingelheim, Bristol-Myers Squibb, 
      Elsevier, GSK, Johnson & Johnson, Medergy, Medscape, Mitsubishi, Myokardia, NIH, 
      Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer, and UCSF. 
      Karen S. Pieper has consultancies with Johnson & Johnson, Element Science, 
      Artivion, and Novartis. Eric D. Peterson has received research grants from 
      Janssen Pharmaceuticals and Eli Lilly and consulted for Janssen Pharmaceuticals 
      and Boehringer Ingelheim. Jonathan P. Piccini has received grants for clinical 
      research from Abbott, American Heart Association, Bayer, Boston Scientific, 
      Janssen Pharmaceuticals, NHLBI, and Philips and serves as a consultant to Abbott, 
      Allergan, ARCA Biopharma, Biotronik, Boston Scientific, Johnson & Johnson, 
      LivaNova, Medtronic, Milestone, Sanofi, Philips, and Up-to-Date. The remaining 
      authors declare no conflict of interest.
EDAT- 2023/08/19 11:44
MHDA- 2023/11/14 06:43
PMCR- 2023/08/18
CRDT- 2023/08/19 00:43
PHST- 2023/07/14 00:00 [revised]
PHST- 2023/06/19 00:00 [received]
PHST- 2023/07/24 00:00 [accepted]
PHST- 2023/11/14 06:43 [medline]
PHST- 2023/08/19 11:44 [pubmed]
PHST- 2023/08/19 00:43 [entrez]
PHST- 2023/08/18 00:00 [pmc-release]
AID - CLC24109 [pii]
AID - 10.1002/clc.24109 [doi]
PST - ppublish
SO  - Clin Cardiol. 2023 Nov;46(11):1398-1407. doi: 10.1002/clc.24109. Epub 2023 Aug 
      18.