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Original Investigation
February 25, 2019

Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection: The Cervical Artery Dissection in Stroke Study (CADISS) Randomized Clinical Trial Final Results

Hugh S. Markus, FMedSci1; Christopher Levi, MD2; Alice King, PhD3; et al Jeremy Madigan, FRCR4; John Norris, MD3; for the Cervical Artery Dissection in Stroke Study (CADISS) Investigators
Author Affiliations
  • 1Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, England
  • 2Department of Neurology, John Hunter Hospital, Hunter New England Local Health District, University of Newcastle, Newcastle, Australia
  • 3Clinical Neuroscience, St George’s University of London, London, England
  • 4Neuroradiology, Atkinson Morley Neuroscience Centre, St George’s Healthcare Foundation Trust, London, England
JAMA Neurol. 2019;76(6):657-664. doi:10.1001/jamaneurol.2019.0072
Key Points

Question  What is the recurrent stroke risk after carotid and vertebral artery dissection, and are antiplatelets or anticoagulants more effective at reducing this risk?

Findings  In this randomized clinical trial, risk of recurrent stroke at 1 year was 2.5%, and there was no difference in recurrence rates or rates of angiographic recanalization with antiplatelets or anticoagulants.

Meaning  The risk of recurrent stroke after carotid and vertebral dissection is low; there was no evidence that antiplatelets or anticoagulants were more effective at reducing this risk.

Abstract

Importance  Extracranial carotid and vertebral artery dissection is an important cause of stroke, particularly in younger individuals. In some but not all observational studies, it has been associated with a high risk of recurrent stroke. Both antiplatelet agents (APs) and anticoagulants (ACs) are used to reduce stroke risk, but whether 1 treatment strategy is more effective is unknown.

Objective  To determine whether AP or AC therapy is more effective in preventing stroke in cervical dissection and the risk of recurrent stroke in a randomized clinical trial setting. A secondary outcome was to determine the effect on arterial imaging outcomes.

Design, Setting, and Participants  Randomized, prospective, open-label international multicenter parallel design study with central blinded review of both clinical and imaging end points. Recruitment was conducted in 39 stroke and neurology secondary care centers in the United Kingdom and 7 centers in Australia between February 24, 2006, and June 17, 2013. One-year follow-up and analysis was conducted in 2018. Two hundred fifty participants with extracranial carotid and vertebral dissection with symptom onset within the last 7 days were recruited. Follow-up data at 1 year were available for all participants.

Interventions  Randomization to AP or AC (heparin followed by warfarin) for 3 months, after which the choice of AP and AC agents was decided by the local clinician.

Main Outcomes and Measures  The primary end point was ipsilateral stroke and death. A planned per protocol (PP) analysis was performed in patients meeting the inclusion criteria following central review of imaging to confirm the diagnosis of dissection. A secondary end point was angiographic recanalization in those with imaging confirmed dissection.

Results  Two hundred fifty patients were randomized (118 carotid and 132 vertebral), 126 to AP and 124 to AC. Mean (SD) age was 49 (12) years. Mean (SD) time to randomization was 3.65 (1.91) days. The recurrent stroke rate at 1 year was 6 of 250 (2.4%) on ITT analysis and 5 of 197 (2.5%) on PP analysis. There were no significant differences between treatment groups for any outcome. Of the 181 patients with confirmed dissection and complete imaging at baseline and 3 months, there was no difference in the presence of residual narrowing or occlusion between those receiving AP (n = 56 of 92) vs those receiving AC (n = 53 of 89) (P = .97).

Conclusions and Relevance  During 12 months of follow-up, the number of recurrent strokes was low. There was no difference between treatment groups in outcome events or the rate of recanalization.

Trial Registration  ISRCTN.com Identifier: CTN44555237

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