TY - JOUR
T1 - Association of intracerebral hemorrhage among patients taking non-Vitamin K antagonist vs Vitamin K antagonist oral anticoagulants with in-hospital mortality
AU - Inohara, Taku
AU - Xian, Ying
AU - Liang, Li
AU - Matsouaka, Roland A.
AU - Saver, Jeffrey L.
AU - Smith, Eric E.
AU - Lee, H. Schwamm
AU - Reeves, Mathew J.
AU - Adrian, F. Hernandez
AU - Bhatt, Deepak L.
AU - Peterson, Eric D.
AU - Fonarow, Gregg C.
N1 - Funding Information:
Funding/Support: The GWTG-Stroke program is providedbytheAmericanHeartAssociation/American Stroke Association. This study is in part supported by the ARAMIS registry with research funding from Daiichi Sankyo, Genentech, and Janssen. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Inohara reported receiving grants from JSPS during the conduct of the study and Pfizer Health Research Foundation and Miyata Cardiac Research Promotion Foundation outside of this work. Dr Xian reported receiving grants from Genentech, Janssen, and Daiichi Sankyo during the study. Dr Saver has served as a consultant and/or on the advisory board of Medtronic, Stryker, and Neuravia. Dr Smith was a member of the Get With The Guidelines (GWTG) steering committee and served on a data safety and monitoring board for Massachusetts General Hospital. Dr Schwamm reported serving as the volunteer chair of the American Heart Association/American Stroke Association GWTG-Stroke Clinical Work Group. Dr Hernandez reported receiving grants and/or personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Daiichi, Janssen, Novartis, and Portola Pharmaceuticals. Dr Bhatt reported receiving nonfinancial support from the American Heart Association; personal fees from Duke Clinical Research Institute (clinical trial steering committees), Mayo Clinic, Population Health Research Institute (clinical trial steering committee), American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org), Belvoir Publications (editor in chief, Harvard Heart Letter), Slack Publications (chief medical editor, Cardiology Today’s Intervention), WebMD (CME steering committees), Elsevier, Society of Cardiovascular Patient Care (secretary/treasurer), HMP Communications (editor in chief, Journal of Invasive Cardiology), Harvard Clinical Research Institute (clinical trial steering committee), Journal of the American College of Cardiology (guest editor, associate editor), Cleveland Clinic, and Mount Sinai School of Medicine; grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company, Roche, Pfizer, Forest Laboratories/ AstraZeneca, Ischemix, Amgen, Eli Lilly, Chiesi, and Ironwood; and other support from FlowCo, PLx Pharma, Takeda, Medscape Cardiology, Regado Biosciences, Boston VA Research Institute, Clinical Cardiology (deputy editor), Veterans Affairs, St Jude Medical, Biotronik, Cardax, American College of Cardiology, Boston Scientific, and Merck. Dr Bhatt has served as chair of the NCDR-ACTION Registry steering committee and VA CART research and publications committee. Dr Peterson reported receiving grants and/or personal fees from Bayer Pharmaceuticals, Janssen Pharmaceuticals, AstraZeneca, Genentech, and the American Heart Association GWTG-Stroke Analytic and has served as a consultant/advisory board member for Janssen, Boehringer Ingelheim, Sanofi, Bayer, Merck, AstraZeneca, Signal Path, and Venable. Dr Fonarow reported serving on the GWTG steering committee; receiving grant funding from the Patient Centered Outcome Research Institute; being an employee of the University of California, which has a patent on an endovascular therapy device; and serving as a consultant for Janssen. No other disclosures were reported.
Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2018/2
Y1 - 2018/2
N2 - IMPORTANCE Although non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH). OBJECTIVE To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 141 311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals. EXPOSURES Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival. MAIN OUTCOMES AND MEASURES In-hospital mortality. RESULTS Among 141 311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1%women), 15 036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6%for warfarin, 26.5%for NOACs, and 22.5%for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5%CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5%CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5%CI, 1.7%to 4.8%]; AOR, 1.21 [97.5%CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD,-5.7%[97.5%CI,-7.3%to-4.2%]; AOR, 0.75 [97.5%CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7%vs 47.1%; ARD,-15.0%[95.5%CI,-26.3%to-3.8%]; AOR, 0.50 [97.5%CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4%vs 31.7%; ARD,-5.0% [97.5%CI,-6.8%to-3.2%]; AOR, 0.77 [97.5%CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant. CONCLUSIONS AND RELEVANCE Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.
AB - IMPORTANCE Although non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH). OBJECTIVE To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 141 311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals. EXPOSURES Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival. MAIN OUTCOMES AND MEASURES In-hospital mortality. RESULTS Among 141 311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1%women), 15 036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6%for warfarin, 26.5%for NOACs, and 22.5%for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5%CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5%CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5%CI, 1.7%to 4.8%]; AOR, 1.21 [97.5%CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD,-5.7%[97.5%CI,-7.3%to-4.2%]; AOR, 0.75 [97.5%CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7%vs 47.1%; ARD,-15.0%[95.5%CI,-26.3%to-3.8%]; AOR, 0.50 [97.5%CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4%vs 31.7%; ARD,-5.0% [97.5%CI,-6.8%to-3.2%]; AOR, 0.77 [97.5%CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant. CONCLUSIONS AND RELEVANCE Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.
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U2 - 10.1001/jama.2017.21917
DO - 10.1001/jama.2017.21917
M3 - Article
C2 - 29372247
AN - SCOPUS:85041649063
SN - 0098-7484
VL - 319
SP - 463
EP - 473
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 5
ER -