Predictors of Recurrent Ischemic Stroke in Patients with Embolic Strokes of Undetermined Source and Effects of Rivaroxaban Versus Aspirin According to Risk Status: The NAVIGATE ESUS Trial

Research output: Contribution to journalArticle

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.

Details

Authors
  • NAVIGATE ESUS Investigators
  • Robert G. Hart
  • Roland C. Veltkamp
  • Patrick Sheridan
  • Mukul Sharma
  • Scott E. Kasner
  • Shrikant I. Bangdiwala
  • George Ntaios
  • Ashkan Shoamanesh
  • Sebastian F. Ameriso
  • Danilo Toni
  • Anna Czlonkowska
  • Arne Lindgren
  • Graeme J. Hankey
  • Kanjana S. Perera
  • Ashfaq Shuaib
  • Shelagh B. Coutts
  • Rubens J. Gagliardi
  • Scott D. Berkowitz
  • Hardi Mundl
  • Gary Peters
  • Stuart J. Connolly
Organisations
External organisations
  • Imperial College London
  • McMaster University
  • University of Pennsylvania
  • Population Health Research Institute, Ontario
  • University of Thessaly
  • Fundacion Para La Lucha Contra Las Enfermedades Neurologicas de La Infancia (FLENI)
  • Sapienza University of Rome
  • Medical University of Warsaw
  • Skåne University Hospital
  • University of Western Australia, Crawley
  • Irmandade da Santa Casa de Misericordia de Sao Paulo
  • Bayer Pharma AG
  • Hamilton Health Sciences
  • Sir Charles Gairdner Hospital
  • University of Alberta Hospital
  • Hotchkiss Brain Institute
  • Bayer Corporation, USA
  • Janssen Research & Development LLC
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Embolic stroke, ESUS, prediction of recurrent stroke, recurrent stroke, rivaroxaban, stroke recurrence
Original languageEnglish
JournalJournal of Stroke and Cerebrovascular Diseases
Publication statusE-pub ahead of print - 2019 May 31
Publication categoryResearch
Peer-reviewedYes