Robert G Hart1, Roland C Veltkamp2, Patrick Sheridan3, Mukul Sharma4, Scott E Kasner5, Shrikant I Bangdiwala6, George Ntaios7, Ashkan Shoamanesh4, Sebastian F Ameriso8, Danilo Toni9, Anna Czlonkowska10, Arne Lindgren11, Graeme J Hankey12, Kanjana S Perera4, Ashfaq Shuaib13, Shelagh B Coutts14, Rubens J Gagliardi15, Scott D Berkowitz16, Hardi Mundl17, Gary Peters18, Stuart J Connolly19. 1. Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada. Electronic address: robert.hart@phri.ca. 2. Imperial College London, London, United Kingdom. 3. Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada. 4. Department of Medicine (Neurology), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada. 5. Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Health Research Methods, Evidence and Impact, McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada. 7. Department of Medicine, University of Thessaly, Larissa, Greece. 8. Institute for Neurological Research, FLENI, Buenos Aires, Argentina. 9. Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy. 10. 2nd Department of Neurology, Institute of Psychiatry and Neurology, Medical University of Warsaw, Warsaw, Poland. 11. Department of Clinical Sciences (Neurology), Department of Neurology and Rehabilitation Medicine, Lund University, Skane University Hospital, Lund, Sweden. 12. Medical School, University of Western Australia, Sir Charles Gairdner Hospital, Perth, Australia. 13. Department of Neurology, University of Alberta Hospital, Edmonton, Alberta, Canada. 14. Department of Clinical Neurosciences, Radiology and Community Health Sciences, Hotchkiss Brain Institute, Calgary, Alberta, Canada. 15. Irmandade da Santa Casa de Misericórdia de São Paulo, Sao Paulo, Brazil. 16. Bayer U.S. L.L.C., Whippany, New Jersey. 17. Bayer AG, Wuppertal, Germany. 18. Janssen Research and Development, LLC, Spring House, Pennsylvania. 19. Department of Medicine (Cardiology), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada.
Abstract
BACKGROUND: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. METHODS: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. RESULTS: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. CONCLUSIONS: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.
RCT Entities:
BACKGROUND:Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. METHODS: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. RESULTS: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. CONCLUSIONS: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.
Authors: Victor J Del Brutto; Han-Christoph Diener; J Donald Easton; Christopher B Granger; Lisa Cronin; Eva Kleine; Claudia Grauer; Martina Brueckmann; Kazunori Toyoda; Peter D Schellinger; Philippe Lyrer; Carlos A Molina; Aurauma Chutinet; Christopher F Bladin; Conrado J Estol; Ralph L Sacco Journal: J Am Heart Assoc Date: 2022-06-03 Impact factor: 6.106