Alvin S Das1, Elif Gökçal1, Robert W Regenhardt1, Andrew D Warren1, Alessandro Biffi1,2, Joshua N Goldstein3, W Taylor Kimberly1, Anand Viswanathan1, Lee H Schwamm1, Jonathan Rosand1,2, Steven M Greenberg1, M Edip Gurol4. 1. Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge Street, Suite 300, Boston, MA, 02114, USA. 2. Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 3. Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 4. Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge Street, Suite 300, Boston, MA, 02114, USA. megurol@mgh.harvard.edu.
Abstract
BACKGROUND AND AIMS: Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) usage confers significant mortality/disability. We aimed to understand the clinical and neuroimaging features associated with developing ICH among DOAC users. METHODS: Clinical and radiological data were collected from consecutive DOAC users with ICH (DOAC-ICH) and age-matched controls without ICH from a single referral center. The frequency/distribution of MRI markers of hemorrhage risk were assessed. Baseline demographics and neuroimaging markers were compared in univariate tests. Significant associations (p < 0.1) were entered into a multivariable regression model to determine predictors of ICH. RESULTS: 86 DOAC-ICH and 94 ICH-free patients were included. Diabetes, coronary artery disease, prior ischemic stroke, smoking history, and antiplatelet usage were more common in ICH patients than ICH-free DOAC users. In the neuroimaging analyses, severe white matter hyperintensities (WMHs), lacunes, cortical superficial siderosis (cSS), and cerebral microbleeds (CMBs) were more common in the ICH cohort than the ICH-free cohort. In the multivariable regression, diabetes [OR 3.53 95% CI (1.05-11.87)], prior ischemic stroke [OR 14.80 95% CI (3.33-65.77)], smoking history [OR 3.08 95% CI (1.05-9.01)], CMBs [OR 4.07 95% CI (1.45-11.39)], and cSS [OR 39.73 95% CI (3.43-460.24)] were independently associated with ICH. CONCLUSIONS: Risk factors including diabetes, prior stroke, and smoking history as well as MRI biomarkers including CMBs and cSS are associated with ICH in DOAC users. Although screening MRIs are not typically performed prior to initiating DOAC therapy, these data suggest that patients of high-hemorrhagic risk may be identified.
BACKGROUND AND AIMS: Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) usage confers significant mortality/disability. We aimed to understand the clinical and neuroimaging features associated with developing ICH among DOAC users. METHODS: Clinical and radiological data were collected from consecutive DOAC users with ICH (DOAC-ICH) and age-matched controls without ICH from a single referral center. The frequency/distribution of MRI markers of hemorrhage risk were assessed. Baseline demographics and neuroimaging markers were compared in univariate tests. Significant associations (p < 0.1) were entered into a multivariable regression model to determine predictors of ICH. RESULTS: 86 DOAC-ICH and 94 ICH-free patients were included. Diabetes, coronary artery disease, prior ischemic stroke, smoking history, and antiplatelet usage were more common in ICH patients than ICH-free DOAC users. In the neuroimaging analyses, severe white matter hyperintensities (WMHs), lacunes, cortical superficial siderosis (cSS), and cerebral microbleeds (CMBs) were more common in the ICH cohort than the ICH-free cohort. In the multivariable regression, diabetes [OR 3.53 95% CI (1.05-11.87)], prior ischemic stroke [OR 14.80 95% CI (3.33-65.77)], smoking history [OR 3.08 95% CI (1.05-9.01)], CMBs [OR 4.07 95% CI (1.45-11.39)], and cSS [OR 39.73 95% CI (3.43-460.24)] were independently associated with ICH. CONCLUSIONS: Risk factors including diabetes, prior stroke, and smoking history as well as MRI biomarkers including CMBs and cSS are associated with ICH in DOAC users. Although screening MRIs are not typically performed prior to initiating DOAC therapy, these data suggest that patients of high-hemorrhagic risk may be identified.
Authors: Manesh R Patel; Kenneth W Mahaffey; Jyotsna Garg; Guohua Pan; Daniel E Singer; Werner Hacke; Günter Breithardt; Jonathan L Halperin; Graeme J Hankey; Jonathan P Piccini; Richard C Becker; Christopher C Nessel; John F Paolini; Scott D Berkowitz; Keith A A Fox; Robert M Califf Journal: N Engl J Med Date: 2011-08-10 Impact factor: 91.245
Authors: A H Katsanos; P D Schellinger; M Köhrmann; A Filippatou; M E Gurol; V Caso; M Paciaroni; F Perren; A V Alexandrov; G Tsivgoulis Journal: Eur J Neurol Date: 2018-07-21 Impact factor: 6.089
Authors: Christian T Ruff; Robert P Giugliano; Eugene Braunwald; Elaine B Hoffman; Naveen Deenadayalu; Michael D Ezekowitz; A John Camm; Jeffrey I Weitz; Basil S Lewis; Alexander Parkhomenko; Takeshi Yamashita; Elliott M Antman Journal: Lancet Date: 2013-12-04 Impact factor: 79.321
Authors: Christopher B Granger; John H Alexander; John J V McMurray; Renato D Lopes; Elaine M Hylek; Michael Hanna; Hussein R Al-Khalidi; Jack Ansell; Dan Atar; Alvaro Avezum; M Cecilia Bahit; Rafael Diaz; J Donald Easton; Justin A Ezekowitz; Greg Flaker; David Garcia; Margarida Geraldes; Bernard J Gersh; Sergey Golitsyn; Shinya Goto; Antonio G Hermosillo; Stefan H Hohnloser; John Horowitz; Puneet Mohan; Petr Jansky; Basil S Lewis; Jose Luis Lopez-Sendon; Prem Pais; Alexander Parkhomenko; Freek W A Verheugt; Jun Zhu; Lars Wallentin Journal: N Engl J Med Date: 2011-08-27 Impact factor: 91.245
Authors: Taku Inohara; Ying Xian; Li Liang; Roland A Matsouaka; Jeffrey L Saver; Eric E Smith; Lee H Schwamm; Mathew J Reeves; Adrian F Hernandez; Deepak L Bhatt; Eric D Peterson; Gregg C Fonarow Journal: JAMA Date: 2018-02-06 Impact factor: 56.272
Authors: Stuart J Connolly; Michael D Ezekowitz; Salim Yusuf; John Eikelboom; Jonas Oldgren; Amit Parekh; Janice Pogue; Paul A Reilly; Ellison Themeles; Jeanne Varrone; Susan Wang; Marco Alings; Denis Xavier; Jun Zhu; Rafael Diaz; Basil S Lewis; Harald Darius; Hans-Christoph Diener; Campbell D Joyner; Lars Wallentin Journal: N Engl J Med Date: 2009-08-30 Impact factor: 91.245
Authors: Jan C Purrucker; Kirsten Haas; Timolaos Rizos; Shujah Khan; Marcel Wolf; Michael G Hennerici; Sven Poli; Christoph Kleinschnitz; Thorsten Steiner; Peter U Heuschmann; Roland Veltkamp Journal: JAMA Neurol Date: 2016-02 Impact factor: 18.302
Authors: Robert P Giugliano; Christian T Ruff; Eugene Braunwald; Sabina A Murphy; Stephen D Wiviott; Jonathan L Halperin; Albert L Waldo; Michael D Ezekowitz; Jeffrey I Weitz; Jindřich Špinar; Witold Ruzyllo; Mikhail Ruda; Yukihiro Koretsune; Joshua Betcher; Minggao Shi; Laura T Grip; Shirali P Patel; Indravadan Patel; James J Hanyok; Michele Mercuri; Elliott M Antman Journal: N Engl J Med Date: 2013-11-19 Impact factor: 91.245
Authors: Duncan Wilson; David J Seiffge; Christopher Traenka; Ghazala Basir; Jan C Purrucker; Timolaos Rizos; Oluwaseun A Sobowale; Hanne Sallinen; Shin-Joe Yeh; Teddy Y Wu; Marc Ferrigno; Rik Houben; Floris H B M Schreuder; Luke A Perry; Jun Tanaka; Marion Boulanger; Rustam Al-Shahi Salman; Hans R Jäger; Gareth Ambler; Clare Shakeshaft; Yusuke Yakushiji; Philip M C Choi; Julie Staals; Charlotte Cordonnier; Jiann-Shing Jeng; Roland Veltkamp; Dar Dowlatshahi; Stefan T Engelter; Adrian R Parry-Jones; Atte Meretoja; David J Werring Journal: Neurology Date: 2017-04-05 Impact factor: 9.910