Elevated International Normalized Ratio Is Associated with Severity of Intracerebral Hemorrhage for Patients Taking Direct Oral Anticoagulants
Abstract Body (Do not enter title and authors here): Introduction/Background: While the international normalized ratio (INR), a marker of functioning of the extrinsic and final common pathways of the coagulation cascade is associated with increased intracerebral hemorrhage (ICH) mortality for patients taking warfarin, it is not understood how it might be associated with outcomes in patients taking direct oral anticoagulants (DOACs), given the inconsistent and variable effect of DOACs on INR. Research Questions/Hypothesis: To determine whether INR is associated with increased ICH severity in patients with recent exposure to a DOAC. Methods/Approach: We included patients taking Apixaban or Rivaroxaban prior to acute presentation with ICH to hospitals participating in the Get With the Guidelines - Stroke registry, a nationwide quality improvement registry. The primary exposure was INR, which we modeled as a continuous variable with restricted cubic splines. The primary endpoint was stroke severity on presentation, measured by the National Institutes of Health Stroke Scale (NIHSS). Secondary endpoints included Glasgow Coma Scale (GCS) <=8 on admission, in-hospital mortality, composite of in-hospital mortality and discharge to hospice, and modified Rankin Scale (mRS) at discharge. We adjusted for key confounding factors, specifically age, sex, race/ethnicity, insurance status, and medical history, while taking into account within-hospital clustering. Results/Data: In total, 13,251 patients were included of whom 7,545 were exposed to apixaban and 5,706 were exposed to rivaroxaban. As shown in Table 1, for patients taking Apixaban, elevated INR was associated with increased likelihood of NIHSS >=21 (aOR 1.02 [95% CI 1.00-1.04, p=0.03] per 0.1 above 1.1) and in-hospital mortality (aOR 1.11 [95% CI 1.05-1.16, p<.001) per 0.1 above 1.1). For patients taking Rivaroxaban, similar trends were seen (aOR 1.21 [95% CI 1.08-1.35, p<.001] per 0.1 up to 1.2 for NIHSS >=21, aOR 1.13, [95% CI 1.09-1.16, p<.001] per 0.1 up to 1.6, for in-hospital mortality). Conclusion(s): Elevated INR at admission is associated with worsened ICH severity for patients taking Apixaban or Rivaroxaban.
Lusk, Jay
( Duke University
, Durham
, North Carolina
, United States
)
Matsouaka, Roland
( Duke University
, Durham
, North Carolina
, United States
)
Xian, Ying
( UTSW
, Dallas
, Texas
, United States
)
Sun, Jie-lena
( Duke University Clinical Research Institute
, Durham
, North Carolina
, United States
)
Mac Grory, Brian
( Duke University Clinical Research Institute
, Durham
, North Carolina
, United States
)
Schwamm, Lee
( Yale School of Medicine
, New Haven
, Connecticut
, United States
)
Smith, Eric
( UNIVERSITY OF CALGARY
, Calgary
, Alberta
, Canada
)
Fonarow, Gregg
( UCLA MEDICAL CENTER
, Los Angeles
, California
, United States
)
Bhatt, Deepak
( Mount Sinai
, New York
, New York
, United States
)
Saver, Jeffrey
( GEFFEN SCHOOL OF MEDICINE AT UCLA
, Los Angeles
, California
, United States
)
Reeves, Mathew
( MICHIGAN STATE UNIVERSITY
, East Lansi
, Michigan
, United States
)
Author Disclosures:
Jay Lusk:DO NOT have relevant financial relationships
| Roland Matsouaka:DO NOT have relevant financial relationships
| Ying Xian:DO NOT have relevant financial relationships
| Jie-Lena Sun:DO NOT have relevant financial relationships
| Brian Mac Grory:No Answer
| Lee Schwamm:DO have relevant financial relationships
;
Consultant:genentech:Active (exists now)
; Consultant:penumbra:Past (completed)
; Consultant:medtronic:Active (exists now)
| Eric Smith:DO NOT have relevant financial relationships
| Gregg Fonarow:DO have relevant financial relationships
;
Consultant:Abbott:Past (completed)
; Consultant:Johnson and Johnson:Past (completed)
; Consultant:Pfizer:Active (exists now)
; Consultant:Novartis:Active (exists now)
; Consultant:Medtronic:Active (exists now)
; Consultant:Merck:Active (exists now)
; Consultant:Eli Lilly:Past (completed)
; Consultant:Boehringer Ingelheim:Past (completed)
; Consultant:Cytokinetics:Active (exists now)
; Consultant:Bayer:Active (exists now)
; Consultant:Astra Zeneca:Past (completed)
; Consultant:Amgen:Past (completed)
| Deepak Bhatt:DO have relevant financial relationships
;
Advisor: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, Stasys:Active (exists now)
; Other (please indicate in the box next to the company name):Trustee: American College of Cardiology; Unfunded Research: FlowCo:Active (exists now)
; Other (please indicate in the box next to the company name):Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions;:Active (exists now)
; Royalties/Patent Beneficiary:Royalties: Elsevier (Editor, Braunwald’s Heart Disease):Active (exists now)
; Researcher: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, 89Bio;:Active (exists now)
; Royalties/Patent Beneficiary:Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent);:Active (exists now)
; Other (please indicate in the box next to the company name):Honoraria: Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee);:Active (exists now)
; Other (please indicate in the box next to the company name):Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum):Active (exists now)
; Other (please indicate in the box next to the company name):Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial);:Active (exists now)
; Consultant:Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene:Active (exists now)
; Other (please indicate in the box next to the company name):Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);:Active (exists now)
| Jeffrey Saver:DO have relevant financial relationships
;
Consultant:Medtronic:Active (exists now)
; Consultant:Astrocyte Pharma:Active (exists now)
| Mathew Reeves:DO NOT have relevant financial relationships
