Randomized Controlled Trial

. 2025 Sep;10(3):871-881.

doi: 10.1177/23969873251315362. Epub 2025 Feb 5.

The 6-months follow-up of the TREAT-CAD trial: Aspirin versus anticoagulation for stroke prevention in patients with cervical artery dissection

Stefan T Engelter^{1

2

3}, Lukas S Enz^{1

3}, Flavia Ravanelli^{1

2}, Josefin E Kaufmann^{1

2}, Henrik Gensicke^{1

2

3}, Sabine Schaedelin³, Andreas R Luft^{4

5}, Christoph Globas⁴, Barbara Goeggel-Simonetti^{6

7

8}, Urs Fischer^{1

8}, Davide Strambo⁹, Georg Kägi^{8

10}, Krassen Nedeltchev^{11

12}, Timo Kahles¹¹, Lars Kellert¹³, Sverre Rosenbaum¹⁴, Regina von Rennenberg^{15

16}, Alex Brehm¹⁷, David Seiffge⁸, Susanne Renaud¹⁸, Tobias Brandt¹⁹, Hakan Sarikaya⁸, Annaelle Zietz^{1

2}, Johannes Wischmann¹³, Alexandros A Polymeris¹, Sandro Fischer^{1

2}, Leo H Bonati^{1

20}, Gian Marco De Marchis^{1

10}, Nils Peters^{1

2}, Christian H Nolte^{15

16

21}, Hanne Christensen¹⁴, Susanne Wegener⁴, Marios-Nikos Psychogios¹⁷, Marcel Arnold⁸, Philippe Lyrer^{1

3}, Christopher Traenka^{1

2}

Affiliations

¹ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
² Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.
³ Department of Clinical Research, University of Basel, Basel, Switzerland.
⁴ Division of Vascular Neurology and Neurorehabilitation, Department of Neurology, University Hospital of Zurich and University of Zurich, Zurich, Switzerland.
⁵ Cereneo, Center for Neurology and Rehabilitation, Vitznau, Switzerland.
⁶ Department of Neuropediatrics, Institute of Pediatrics of Southern Switzerland, San Giovanni Hospital, Bellinzona.
⁷ Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
⁸ Department of Neurology, University Hospital Bern, University of Bern, Bern, Switzerland.
⁹ Stroke Center, Service of Neurology, Department of Clinical Neurosciences, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland.
¹⁰ Department of Neurology and Stroke Center, Cantonal Hospital St.Gallen, St.Gallen, Switzerland.
¹¹ Department of Neurology and Stroke Center, Cantonal Hospital Aarau, Aarau, Switzerland.
¹² Department of Neurology, University of Bern, Bern, Switzerland.
¹³ Department of Neurology, Ludwig Maximilian University (LMU), Munich, Germany.
¹⁴ Department of Neurology, Copenhagen University Hospital, Bispebjerg, Copenhagen, Denmark.
¹⁵ Center for Stroke Research Berlin (CSB), Charite-Universitätsmedizin Berlin, Berlin, Germany.
¹⁶ Department of Neurology and Experimental Neurology, Charite-Universitätsmedizin Berlin, Berlin, Germany.
¹⁷ Department of Neuroradiology, University Hospital Basel, Basel, Switzerland.
¹⁸ Division of Neurology and Stroke Unit, Neuchâtel Hospital Network, Neuchâtel, Switzerland.
¹⁹ Swiss National Accident Insurance Fund SUVA, Lucerne, Switzerland.
²⁰ Research Department, Reha Rheinfelden, Rheinfelden, Switzerland.
²¹ Berlin Institute of Health at Charite, (BIH), Charite-Universitätsmedizin Berlin, Berlin, Germany.

PMID: 39910883
PMCID: PMC11803590
DOI: 10.1177/23969873251315362

Randomized Controlled Trial

The 6-months follow-up of the TREAT-CAD trial: Aspirin versus anticoagulation for stroke prevention in patients with cervical artery dissection

Stefan T Engelter et al. Eur Stroke J. 2025 Sep.

. 2025 Sep;10(3):871-881.

doi: 10.1177/23969873251315362. Epub 2025 Feb 5.

Authors

Affiliations

¹ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
² Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.
³ Department of Clinical Research, University of Basel, Basel, Switzerland.
⁴ Division of Vascular Neurology and Neurorehabilitation, Department of Neurology, University Hospital of Zurich and University of Zurich, Zurich, Switzerland.
⁵ Cereneo, Center for Neurology and Rehabilitation, Vitznau, Switzerland.
⁶ Department of Neuropediatrics, Institute of Pediatrics of Southern Switzerland, San Giovanni Hospital, Bellinzona.
⁷ Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
⁸ Department of Neurology, University Hospital Bern, University of Bern, Bern, Switzerland.
⁹ Stroke Center, Service of Neurology, Department of Clinical Neurosciences, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland.
¹⁰ Department of Neurology and Stroke Center, Cantonal Hospital St.Gallen, St.Gallen, Switzerland.
¹¹ Department of Neurology and Stroke Center, Cantonal Hospital Aarau, Aarau, Switzerland.
¹² Department of Neurology, University of Bern, Bern, Switzerland.
¹³ Department of Neurology, Ludwig Maximilian University (LMU), Munich, Germany.
¹⁴ Department of Neurology, Copenhagen University Hospital, Bispebjerg, Copenhagen, Denmark.
¹⁵ Center for Stroke Research Berlin (CSB), Charite-Universitätsmedizin Berlin, Berlin, Germany.
¹⁶ Department of Neurology and Experimental Neurology, Charite-Universitätsmedizin Berlin, Berlin, Germany.
¹⁷ Department of Neuroradiology, University Hospital Basel, Basel, Switzerland.
¹⁸ Division of Neurology and Stroke Unit, Neuchâtel Hospital Network, Neuchâtel, Switzerland.
¹⁹ Swiss National Accident Insurance Fund SUVA, Lucerne, Switzerland.
²⁰ Research Department, Reha Rheinfelden, Rheinfelden, Switzerland.
²¹ Berlin Institute of Health at Charite, (BIH), Charite-Universitätsmedizin Berlin, Berlin, Germany.

PMID: 39910883
PMCID: PMC11803590
DOI: 10.1177/23969873251315362

Abstract

Introduction: Cervical artery dissection is a major cause of stroke in the young. The optimal choice and duration of antithrombotic treatment for stroke prevention are debated, particularly beyond 3 months after symptom onset.

Patients and methods: TREAT-CAD (TREATment of Cervical Artery Dissection) was a randomized controlled trial with blinded outcome assessment comparing non-inferiority of aspirin to anticoagulation (Vitamin-K-antagonists) in participants with symptomatic, Magnetic-Resonance-(MR)-imaging-verified cervical artery dissection. TREAT-CAD could not establish non-inferiority of aspirin to anticoagulation at 3 months. Thereafter participants could continue antithrombotic medication and obtained a standardized assessment of clinical and MR-Imaging outcomes between 3 and 6 months. As crossover to the other treatment arm was possible, we performed an as-treated analysis as main analysis. The main outcomes were new clinical (ischemic stroke, intracranial/major extracranial bleeding, or death) and new MR-Imaging outcomes (ischemic or hemorrhagic brain lesions).

Results: Among the 122 participants in the as-treated analysis, 3/93 (3.2%) aspirin-treated participants had new clinical (n = 1) and MRI-outcomes (n = 2) between 3 and 6 months while 1/29 (3.4%) anticoagulated participants had an MRI-outcome (n = 1). All outcome events were hemorrhagic while ischemic events were absent. No deaths occurred. This yields an absolute difference of 0.2% (95% CI -8.0% to 7.5%, p = 1.0).

Discussion and conclusion: During the extended follow-up period of a controlled randomized trial comparing aspirin to anticoagulation in cervical artery dissection, outcomes between 3 and 6 months after randomization occurred rarely, similarly often in both groups and were exclusively hemorrhagic events. Thus, studies balancing benefits versus harms of antithrombotic treatment beyond 3 months are warranted.

Registration: ClinicalTrials.gov: NCT02046460. https://clinicaltrials.gov/ct2/show/NCT02046460.

Keywords: Cervical artery dissection; stroke in the young; treatment; treatment duration.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: STE reports grants from Swiss National Science Foundation, Swiss Heart Foundation, Freiwillige Akademische Gesellschaft Basel, University of Basel, the University Hospital Basel, and the Science Fund Rehabilitation of the University Department of Geriatric Medicine Felix Platter Basel during the conduct of the study. LSE reports a grant from the University Hospital Basel during the conduct of the study. 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. UF reports grants from Medtronic and consultancy to Medtronic, Stryker, and CSL Behring, outside of the submitted work. LK funding for travel or speaker honoraria from Bayer Vital, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, and Pfizer, 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 Universi-ty 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. 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. 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. SW reports grants by the Swiss National Science Foundation, the UZH Clinical research priority program (CRPP) stroke, the Swiss Heart foundation, the Zurich Neuroscience Center (ZNZ), the Baugarten Foundation, Koetser Foundation, Hartmann-Müller-Foundation, and Olga-Mayenfish foundation; speaker honoraria from Amgen, Springer, Teva Pharma, ADVISIS-AG, FOMF, Astra Zeneca, and a consultancy fee from Bayer and Novartis; all 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. MP reports grants from the Swiss National Science Foundation (SNF) for the DISTAL trial (33IC30_198783), ICARUS (32003B_220118) and TECNO trial (32003B_204977), Grant from Bangerter-Rhyner Stiftung for the DISTAL trial. Unrestricted Grants for the DISTAL trial from Stryker Neurovascular Inc., Phenox GmbH, Penumbra Inc. and Rapid Medical Inc., Sponsor-PI SPINNERS trial (Funded by a Siemens Healthineers AG Grant), Research agree-ment with Siemens Healthineers AG, Local PI for the ACT in STROKE, ASSIST, EXCEL-LENT, TENSION, COATING, SURF and ESCAPE-NEXT trials. Speaker fees: Stryker Neurovascular Inc., Medtronic Inc., Penumbra Inc., Acandis GmbH, Phenox GmbH, Siemens Healthineers AG, outside of 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. 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. All other authors declare no competing interests.

Figures

**Figure 1.**
Trial flow chart. The 3 month per-protocol analysis has been reported previously.

See this image and copyright information in PMC

References

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The 6-months follow-up of the TREAT-CAD trial: Aspirin versus anticoagulation for stroke prevention in patients with cervical artery dissection

Affiliations

The 6-months follow-up of the TREAT-CAD trial: Aspirin versus anticoagulation for stroke prevention in patients with cervical artery dissection

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

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Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical

Research Materials

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