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Antithrombotic Treatment for Cervical Artery Dissection: A Systematic Review and Individual Patient Data Meta-Analysis.

Accepted version
Peer-reviewed

Type

Article

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Authors

Kaufmann, Josefin E 
Gensicke, Henrik 
Wegener, Susanne 
Michel, Patrik 

Abstract

IMPORTANCE: Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients. OBJECTIVE: To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection. DATA SOURCES: PubMed.gov, Cochrane database, Embase, and ClinicalTrials.gov were searched from inception to August 1, 2023. STUDY SELECTION: Randomized clinical trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets vs anticoagulation) in patients with cervical artery dissection were included in the meta-analysis. The primary end point was required to include a composite of (1) any stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. DATA EXTRACTION/SYNTHESIS: Two independent investigators performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and inconsistencies were resolved by a principal investigator. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of (1) ischemic stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative association with the outcome were performed. Logistic regression was performed using the maximum penalized likelihood method including interaction in the subgroup analyses. RESULTS: Two randomized clinical trials, Cervical Artery Dissection in Stroke Study and Cervical Artery Dissection in Stroke Study and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection, were identified, of which all participants were eligible. A total of 444 patients were included in the intention-to-treat population and 370 patients were included in the per-protocol population. Baseline characteristics were balanced. There were fewer primary end points in those randomized to anticoagulation vs antiplatelet therapy (3 of 218 [1.4%] vs 10 of 226 [4.4%]; odds ratio [OR], 0.33 [95% CI, 0.08-1.05]; P = .06), but the finding was not statistically significant. In comparison with aspirin, anticoagulation was associated with fewer strokes (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = .01) and more bleeding events (2 vs 0). CONCLUSIONS AND RELEVANCE: This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.

Description

Keywords

Humans, Vertebral Artery Dissection, Fibrinolytic Agents, Platelet Aggregation Inhibitors, Anticoagulants, Randomized Controlled Trials as Topic, Stroke, Carotid Artery, Internal, Dissection

Journal Title

JAMA Neurol

Conference Name

Journal ISSN

2168-6149
2168-6157

Volume Title

Publisher

American Medical Association (AMA)
Sponsorship
British Heart Foundation (RE/18/1/34212)
British Heart Foundation (RG/F/22/110052)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Alzheimer's Society (573 (AS-RF-21-017))
This research project as a doctoral thesis was funded by the Goldschmidt-Jacobson foundation. The CADISS study was supported by a project grant from the Stroke Association, and recruitment was supported by the English National Institute for Health Research Stroke Research Network. The TREAT-CAD trial was funded by Swiss National Science Foundation (grant 140340), Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, and Academic Society Basel, and we gratefully acknowledge the work of the data safety monitoring board and the clinical event adjudicators. The Stroke Research Group at the University of Cambridge has received funding from the Cambridge British Heart Foundation Centre of Research Excellence (RE/18/1/34212) and a British Heart Foundation programme grant (RG/F/22/110052), and infrastructural support was provided by the Cambridge University Hospitals NIHR Biomedical Research Centre (IS-BRC-1215-20014). ELH is funded by the Alzheimer’s Society (AS-RF-21-017). The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or UK Department of Health and Social Care.