Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2023 Jun 20;329(23):2038-2049.
doi: 10.1001/jama.2023.8073.

Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke

Brian Mac Grory  1   2 , DaJuanicia N Holmes  2 , Roland A Matsouaka  2   3 , Shreyansh Shah  1 , Cherylee W J Chang  1 , Richard Rison  4 , Jenelle Jindal  5 , Christine Holmstedt  6 , William R Logan  7 , Candy Corral  8 , Jason S Mackey  9 , Joey R Gee  10 , David Bonovich  11 , James Walker  12 , Toby Gropen  13 , Curtis Benesch  14 , Jonathan Dissin  15 , Hemant Pandey  16 , David Wang  17 , Martin Unverdorben  18 , Adrian F Hernandez  2   19 , Mathew Reeves  20 , Eric E Smith  21 , Lee H Schwamm  22   23 , Deepak L Bhatt  24 , Jeffrey L Saver  25 , Gregg C Fonarow  26   27 , Eric D Peterson  28 , Ying Xian  29   30
Affiliations
Observational Study

Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke

Brian Mac Grory et al. JAMA. .

Abstract

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications.

Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice.

Design, setting, and participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included.

Exposure: VKA use within the 7 days prior to hospital arrival.

Main outcome and measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice.

Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups.

Conclusions and relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Mac Grory reported receipt of grants from the National Institutes of Health. Dr Hernandez reported receipt of grants from Janssen, Genentech, and Daiichi and personal fees from AstraZeneca, Merck, Bayer, and Boehringer Ingelheim. Dr Schwamm reported receipt of personal fees from Genentech, Medtronic, and Penumbra and grants from Medtronic. Dr Bhatt reported advisory board membership for Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; board of directors membership for Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), the Society of Cardiovascular Patient Care, and TobeSoft; being inaugural chair of the American Heart Association Quality Oversight Committee; consultancy for Broadview Ventures and Hims; data monitoring committee membership for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute), Boston Scientific, Cleveland Clinic, Contego Medical, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Novartis, the Population Health Research Institute, and Rutgers University; receipt of honoraria from the American College of Cardiology, Arnold and Porter law firm, Baim Institute for Clinical Research, Belvoir Publications, Canadian Medical and Surgical Knowledge Translation Research Group, Cowen and Company, Duke Clinical Research Institute, HMP Global, the Journal of the American College of Cardiology, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, the Population Health Research Institute, Slack Publications, the Society of Cardiovascular Patient Care, WebMD, and Wiley; serving as deputy editor of Clinical Cardiology, chair of the NCDR-ACTION Registry Steering Committee, and chair of the VA CART Research and Publications Committee; being named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned it to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); receipt of research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; receipt of royalties from Elsevier; serving as site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; serving as trustee for the American College of Cardiology; and conducting unfunded research for FlowCo and Takeda. Dr Saver reported receipt of personal fees from Medtronic, MIVI, Rapid Medical, Biogen, and Roche. Dr Fonarow reported receipt of grants from the Patient-Centered Outcomes Research Institute and nonfinancial support from the GWTG Steering Committee and being an employee of the University of California, which has a patent on an endovascular device. Dr Peterson reported receipt of grants from Amgen and Esperion and personal fees from Novo Nordisk. Dr Xian reported receipt of personal fees from Boehringer Ingelheim. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow of Patients Included in the Study
EVT indicates endovascular therapy; INR, international normalized ratio; NIHSS, National Institutes of Health Stroke Scale. Trained hospital personnel use a patient management tool to collect data on consecutive patients with acute ischemic stroke admitted to each participating hospital. aPatients with recent use of vitamin K antagonist or no use of any anticoagulant prior to stroke.
Figure 2.
Figure 2.. Unadjusted and Adjusted Association of Presentation INR With sICH and Life-threatening Systemic Hemorrhage
sICH indicates symptomatic intracranial hemorrhage. This figure includes only patients taking a vitamin K antagonist and with international normalized ratio (INR) data recorded at presentation (n = 2415). Logistic regression modeling was conducted to examine the unadjusted and adjusted relationship between INR and the end point in question. Propensity scores calculated using overlap weighting were used for adjustment. The Stone and Koo additive spline method with 4 knots was fit to generate the plots. Under each graph, the numbers of patients and events are shown for each outcome for a given INR range. For example, there were 106 sICHs occurring for 1552 patients with an INR of 1.0 to 1.7 and 56 sICHs occurring for 641 patients with an INR of 1.8 to 2.5. Because of clinical relevance, each graph starts at INR = 1.
See this image and copyright information in PMC

Comment in

References

    1. Goyal M, Menon BK, van Zwam WH, et al. ; HERMES Collaborators . Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723-1731. doi: 10.1016/S0140-6736(16)00163-X - DOI - PubMed
    1. Saver JL, Goyal M, Bonafe A, et al. ; SWIFT PRIME Investigators . Stent-retriever thrombectomy after intravenous t-PA vs t-PA alone in stroke. N Engl J Med. 2015;372(24):2285-2295. doi: 10.1056/NEJMoa1415061 - DOI - PubMed
    1. Jovin TG, Chamorro A, Cobo E, et al. ; REVASCAT Trial Investigators . Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015;372(24):2296-2306. doi: 10.1056/NEJMoa1503780 - DOI - PubMed
    1. Goyal M, Demchuk AM, Menon BK, et al. ; ESCAPE Trial Investigators . Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372(11):1019-1030. doi: 10.1056/NEJMoa1414905 - DOI - PubMed
    1. Campbell BC, Mitchell PJ, Kleinig TJ, et al. ; EXTEND-IA Investigators . Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015;372(11):1009-1018. doi: 10.1056/NEJMoa1414792 - DOI - PubMed

Publication types

MeSH terms