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. 2024 Feb 9;81(4):363-372.
doi: 10.1001/jamaneurol.2024.0221. Online ahead of print.

Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage

Kevin N Sheth  1 , Nicole Solomon  2 , Brooke Alhanti  2 , Steven R Messe  3 , Ying Xian  4 , Deepak L Bhatt  5 , J Claude Hemphill  6 , Jennifer A Frontera  7 , Raymond C Chang  8 , Ilya M Danelich  8 , Joanna Huang  8 , Lee Schwamm  9 , Eric E Smith  10 , Joshua N Goldstein  11 , Brian Mac Grory  12 , Gregg C Fonarow  13 , Jeffrey L Saver  14
Affiliations

Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage

Kevin N Sheth et al. JAMA Neurol. .

Abstract

Importance: Intracerebral hemorrhage (ICH) is the deadliest stroke subtype, and mortality rates are especially high in anticoagulation-associated ICH. Recently, specific anticoagulation reversal strategies have been developed, but it is not clear whether there is a time-dependent treatment effect for door-to-treatment (DTT) times in clinical practice.

Objective: To evaluate whether DTT time is associated with outcome among patients with anticoagulation-associated ICH treated with reversal interventions.

Design, setting, and participants: This cohort study used data from the American Heart Association Get With The Guidelines-Stroke quality improvement registry. Patients with ICH who presented within 24 hours of symptom onset across 465 US hospitals from 2015 to 2021 were included. Data were analyzed from January to September 2023.

Exposures: Anticoagulation-associated ICH.

Main outcomes and measures: DTT times and outcomes were analyzed using logistic regression modeling, adjusted for demographic, history, baseline, and hospital characteristics, with hospital-specific random intercepts to account for clustering by site. The primary outcome of interest was the composite inpatient mortality and discharge to hospice. Additional prespecified secondary outcomes, including functional outcome (discharge modified Rankin Scale score, ambulatory status, and discharge venue), were also examined.

Results: Of 9492 patients with anticoagulation-associated ICH and documented reversal intervention status, 4232 (44.6%) were female, and the median (IQR) age was 77 (68-84) years. A total of 7469 (78.7%) received reversal therapy, including 4616 of 5429 (85.0%) taking warfarin and 2856 of 4069 (70.2%) taking a non-vitamin K antagonist oral anticoagulant. For the 5224 patients taking a reversal intervention with documented workflow times, the median (IQR) onset-to-treatment time was 232 (142-482) minutes and the median (IQR) DTT time was 82 (58-117) minutes, with a DTT time of 60 minutes or less in 1449 (27.7%). A DTT time of 60 minutes or less was associated with decreased mortality and discharge to hospice (adjusted odds ratio, 0.82; 95% CI, 0.69-0.99) but no difference in functional outcome (ie, a modified Rankin Scale score of 0 to 3; adjusted odds ratio, 0.91; 95% CI, 0.67-1.24). Factors associated with a DTT time of 60 minutes or less included White race, higher systolic blood pressure, and lower stroke severity.

Conclusions and relevance: In US hospitals participating in Get With The Guidelines-Stroke, earlier anticoagulation reversal was associated with improved survival for patients with ICH. These findings support intensive efforts to accelerate evaluation and treatment for patients with this devastating form of stroke.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sheth reported grants from the National Institutes of Health, American Heart Association, Hyperfine, Biogen, and Bard; serves on the data safety monitoring board for Zoll and Sense; serves on the scientific advisory board for CSL Behring, Astrocyte, and Rhaeos; and holds equity in Alva outside the submitted work; in addition, Dr Sheth had a patent for Alva issued. Dr Messe reported a patent for monitoring of upper limb movements to detect stroke pending and holds equity in Neuralert Technologies. Dr Xian reported personal fees from Boehringer Ingelheim and grants from the National Institute on Aging during the conduct of the study. Dr Bhatt reported nonfinancial support from the American Heart Association during the conduct of the study; serves on the advisory board for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; serves on the Board of Directors for American Heart Association New York City, Angiowave, Bristol Myers Squibb, DRS.LINQ, High Enroll; owns stock in Angiowave, Bristol Myers Squibb, DRS.LINQ, and High Enroll; serves as a consultant for Broadview Ventures, GlaxoSmithKline, Hims, SFJ Pharmaceuticals, and Youngene Therapeutics; serves on the data monitoring committee 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, Population Health Research Institute, and Rutgers University; has received honoraria from American College of Cardiology, Arnold and Porter Law Firm, Baim Institute for Clinical Research, Belvoir Publications, Canadian Medical and Surgical Knowledge Translation Research Group, CSL Behring, Cowen and Company, Duke Clinical Research Institute, HMP Global, Journal of the American College of Cardiology, K2P, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, Population Health Research Institute, WebMD, and Wiley; is Deputy Editor of Clinical Cardiology; has a patent for sotagliflozin assigned to Brigham and Women’s Hospital, who assigned to Lexicon; has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, 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, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier; is a site coinvestigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical, Philips, SpectraWAVE, Svelte, and Vascular Solutions; is a trustee for the American College of Cardiology; and has received unfunded research support from FlowCo. Dr Frontera reported being a site principal investigator for AstraZeneca outside the submitted work. Dr Chang holds stock in AstraZeneca outside the submitted work. Dr Danelich holds stock in AstraZeneca. Dr Huang reported personal fees from AstraZeneca during the conduct of the study. Dr Schwamm reported personal fees from Genentech, Penumbra, and Medtronic outside the submitted work. Dr Smith reported grants from SFJ Pharmaceuticals outside the submitted work. Dr Goldstein reported grants from Octapharma, Takeda, the National Institutes of Health, and Pfizer; personal fees from AstraZeneca and CSL Behring; and holds stock in NControl and Cayuga outside the submitted work. Dr Mac Grory reported grants from the National Institutes of Health and American Heart Association outside the submitted work. Dr Fonarow reported personal fees from AstraZeneca, Amgen, Bayer, Eli Lilly, Janssen, Merck, Novartis, and Pfizer outside the submitted work and is Associate Section Editor of JAMA Cardiology. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram Showing Study Population Screening, Eligibility, and Inclusion
ED indicates emergency department; ICH, intracerebral hemorrhage; INR, international normalized ratio; OAC, oral anticoagulants.
Figure 2.
Figure 2.. Distribution of Patients by 15-Minute Increments in Door-to-Treatment (DTT) Time Windows
See this image and copyright information in PMC

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