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Meta-Analysis
. 2024 Jun 1;81(6):630-637.
doi: 10.1001/jamaneurol.2024.1141.

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

Josefin E Kaufmann  1   2 , Eric L Harshfield  3 , Henrik Gensicke  1   2 , Susanne Wegener  4 , Patrik Michel  5 , Georg Kägi  6   7 , Krassen Nedeltchev  8 , Lars Kellert  9   10 , Sverre Rosenbaum  11 , Christian H Nolte  12   13 , Hanne Christensen  11 , Marcel Arnold  6 , Philippe Lyrer  1 , Christopher Levi  14 , Philip M Bath  15 , Stefan T Engelter  1   2 , Christopher Traenka  1   2 , Hugh S Markus  3 ; CADISS and TREAT-CAD Investigators
Collaborators, Affiliations
Meta-Analysis

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

Josefin E Kaufmann et al. JAMA Neurol. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kaufmann reported receiving grants from the Goldschmidt-Jacobson Foundation during the conduct of the study; and grants from the Internal Pool of the University Hospital of Basel outside the submitted work. Dr Harshfield reported receiving grants from the Alzheimer's Society, BHF program grant, and Cambridge NIHR Biomedical Research Centre during the conduct of the study; and grants from Cambridge BHF Centre of Research Excellence outside the submitted work. Dr Michel reported receiving grants from the Swiss National Science Foundation, Swiss Heart Foundation, and Faculty of Biology and Medicine of Lausanne University outside the submitted work. Dr Kellert reported receiving funding for travel or speaker honoraria from Alexion, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol-Meyer-Squibb, Daiichi Sankyo, and Pfizer outside the submitted work. Dr Nolte reported receiving speaker honoraria from Abbott, Alexion, AstraZeneca, BMS, Daiichi Sankyo, Novartis, Pfizer, Portola, and Takeda. Dr Arnold reported receiving grants from the Swiss National Science Foundation for Treat-CAD during the conduct of the study; and scientific advisory board fees from Amgen; lecture fees from AstraZeneca; lecture and scientific advisory board fees from Bayer; scientific advisory board fees from BMS; scientific advisory board fees from Boehringer Ingelheim; lecture fees from Covidien; scientific advisory board fees from Daiichi Sankyo; lecture and scientific advisory board fees from Medtronic; and scientific advisory board fees from Novartis, Novo Nordisk, Pfizer, and Sanofi outside the submitted work. Dr Bath reported receiving advisory board fees from CoMind, DiaMedica, Phagenesis, and Roche outside the submitted work. Dr Engelter reported receiving grants from the Swiss National Science Foundation, Swiss Heart Foundation, Freiwillige Akademische Gesellschaft Basel, University of Basel, and University Hospital Basel during the conduct of the study. Dr Traenka reported receiving grants from University Hospital Basel, Novartis Foundation for Biological and Medical Research, Swiss Heart Foundation, Bangerter Foundation Basel, and FAG Basel outside the submitted work. Dr Markus reported receiving grants from Stroke Association funded CADISS study during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Patient Flowchart
CADISS indicates Cervical Artery Dissection in Stroke Study; TREAT-CAD, Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection. aTwo patients in each group met more than 1 of these criteria.
Figure 2.
Figure 2.. Primary End Point and Subgroup Analyses
aAmaurosis fugax, 1 (information not available [NA]). bInitial thrombolysis, 1 (information NA). cOcclusion, 26 (information NA). dPatients with a dissection of the carotid artery and the vertebral artery were removed in the subgroup site of dissection (n = 3). eDissecting aneurysm, 21 (information NA).
See this image and copyright information in PMC

References

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