Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial
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Background: Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines—based on available evidence from mostly observational studies—suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. Methods: We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0–3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. Findings: Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI −4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. Interpretation: Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection. Funding: Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | The Lancet Neurology |
| Vol/bind | 20 |
| Udgave nummer | 5 |
| Sider (fra-til) | 341-350 |
| Antal sider | 10 |
| ISSN | 1474-4422 |
| DOI | |
| Status | Udgivet - maj 2021 |
Bibliografisk note
Funding Information:
We gratefully acknowledge the work of the data safety monitoring board and the clinical event adjudicators. This 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.
Funding Information:
STE reports grants from Swiss National Science Foundation, Swiss Heart Foundation, Freiwillige Akademische Gesellschaft Basel, University of Basel, and University Hospital Basel, during the conduct of the study. CT reports grants from Swiss Heart Foundation, University of Basel, Bangerter-Rhyner Foundation, and Freiwillige Akademische Gesellschaft Basel; and travel honoraria from Bayer, outside of the submitted work. MA reports grants from Swiss National Science Foundation and Swiss Heart Foundation, during the conduct of the study; personal fees from Bayer, Bristol Myers Squibb, Covidien, Medtronic, Amgen, Daiichi Sankyo, Nestle Health Science, and Boehringer Ingelheim, outside of the submitted work. LHB reports grants from Swiss National Science Foundation, during the conduct of the study; and grants from Swiss Heart Foundation and University of Basel; grants and non-financial support from AstraZeneca; personal fees from Amgen, Bristol Myers Squibb, and Claret Medical; and personal fees and non-financial support from Bayer, outside of the submitted work. UF reports grants from Medtronic and consultancy to Medtronic, Stryker, and CSL Behring, outside of the submitted work. HG reports advisory board honoraria from Daiichi Sankyo and funding for travel from Bristol Myers Squibb and Pfizer, outside of the submitted work. BGS reports grants from Swiss National Science Foundation, during the conduct of the study. JG reports grants from Medtronic, outside of the submitted work. JH reports personal fees from Pfizer, outside of the submitted work. LK reports funding for travel or speaker honoraria from Bayer Vital, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, and Pfizer, outside of the submitted work. ARL reports personal fees from Amgen and Bayer, outside of the submitted work. PL reports grants from Bayer, Swiss National Science Foundation, and ProPatient Foundation of the University Hospital Basel; travel grants from Bayer and Pfizer; advisory board compensation from Bayer, Pfizer, Daiichi Sankyo, Bristol Myers Squibb, Recordati, and Amgen; and compensation for research activities from Sanofi and Acticor, outside of the submitted work. PM reports grants from University Hospital Basel for and during the conduct of the study; grants from Swiss National Science Foundation, Swiss Heart Foundation, ERISTA (Bristol Myers Squibb and Pfizer) programme; and personal fees from Medtronic all used for education and research, outside of the submitted work. CHN reports patient fee compensation from University Hospital Basel, during the conduct of the study; and payments for lectures from Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, and Abbott, outside of the submitted work. NP reports speaker honoraria from Vifor; consulting fees from Daiichi Sankyo; and travel funding from Bristol Myers Squibb and Pfizer, outside of the submitted work. GS reports travel support from Bayer, outside of the submitted work. SW reports personal fees from Amgen and Bayer, outside of the submitted work. All other authors declare no competing interests.
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