Antiplatelet Therapy vs. Anticoagulation in Cervical Artery Dissection: Evolving Evidence and Ongoing Questions

The debate over whether antiplatelet therapy or anticoagulation is superior for preventing subsequent cerebral ischaemic events in patients with cervical artery dissection (CeAD) remains unresolved. Despite significant research efforts, including two pivotal randomised controlled trials (RCTs)—the Cervical Artery Dissection in Stroke Study (CADISS)^1,2 and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection (TREAT-CAD)^3,4—a clear consensus has yet to emerge.

Both trials compared vitamin K antagonists for anticoagulation with primarily single antiplatelet therapy, although CADISS also permitted dual antiplatelet therapy. Neither the individual trials nor the subsequent study-level meta-analyses featured in the European Stroke Organisation (ESO) Guidelines⁵ have definitively answered this clinically pertinent question. However, recent studies have provided new insights.

An individual participant data meta-analysis combining CADISS and TREAT-CAD trial data⁶ revealed a non-significant reduction in the composite primary endpoint – ischemic stroke and major bleeding – among participants randomised to anticoagulation (3 of 218 [1.4%] vs (antiplatelets) 10 of 226 [4.4%]; odds ratio , 0.33 [95% CI, 0.08-1.05]; P = 0.06). When analysing ischaemic stroke alone, anticoagulation demonstrated a significant benefit (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = 0.01), suggesting a potential advantage of anticoagulation in stroke prevention.⁶

Adding to the discussion, the recently published STOP-CAD observational study compared anticoagulation (including both vitamin K antagonists and direct oral anticoagulants ) with antiplatelet therapy (both single and dual regimens) in 3,636 patients with CeAD.⁷ The study found no significant difference between the two treatment groups in preventing ischemic stroke at six months post-CeAD diagnosis (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P=0.67). However, anticoagulation was significantly associated with an increased risk of major haemorrhagic events (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P = 0.009).⁷

A comprehensive systematic review and meta-analysis integrating observational data from STOP-CAD with RCT data from CADISS and TREAT-CAD further refined our understanding.⁸ It demonstrated that anticoagulation significantly outperformed antiplatelet therapy in preventing ischaemic strokes (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P = 0.02; I2=0%). The number needed to treat with anticoagulation to prevent one ischaemic stroke was 50, while the number needed to harm for causing one major haemorrhage was 135 – suggesting a net clinical benefit favouring anticoagulation.⁸

However, caution is warranted. The STOP-CAD study influenced the meta-analysis’s favourable outcome for anticoagulation.⁸ This highlights the urgent need for additional RCTs to validate these findings and provide the highest level of evidence. Future trials should incorporate modern antithrombotic agents, such as DOACs, to align with current clinical practice.⁶

Additionally, the optimal duration of antithrombotic therapy in CeAD remains an open question.  Long-term data from TREAT-CAD found no ischaemic events between 3 to 6 months post-diagnosis, although four haemorrhagic events were reported among 122 participants during this period.⁹ Another study involving 1,390 patients with a median follow-up of 36 months observed that the rates of subsequent ischaemic cerebral events were comparable between those who received antithrombotic treatment and those who did not (5.0% vs. 4.5%; log-rank test, P = 0.53).¹⁰ These findings raise critical questions: How long should antithrombotic therapy be continued in patients with CeAD? At what point does the risk of haemorrhagic events surpass the benefit of preventing cerebral ischaemic events?

In summary, current evidence suggests a potential net clinical benefit of anticoagulation over antiplatelet therapy in preventing ischaemic strokes in patients with CeAD.^6-8 However, the influence of observational data on these conclusions,⁸ the evolving landscape of antithrombotic agents, and the unanswered questions surrounding treatment duration highlight the need for further high-quality RCTs.⁶

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References

1. investigators Ct, Markus HS, Hayter E, et al. Antiplatelet treatment compared with anticoagulation treatment for cervical artery dissection (CADISS): a randomised trial. Lancet Neurol 2015; 14(4): 361-7.
2. Markus HS, Levi C, King A, Madigan J, Norris J, Cervical Artery Dissection in Stroke Study I. Antiplatelet Therapy vs Anticoagulation Therapy in Cervical Artery Dissection: The Cervical Artery Dissection in Stroke Study (CADISS) Randomized Clinical Trial Final Results. JAMA Neurol 2019; 76(6): 657-64.
3. Engelter ST, Traenka C, Gensicke H, et al. Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial. Lancet Neurol 2021; 20(5): 341-50.
4. Traenka C, Gensicke H, Schaedelin S, et al. Biomarkers and antithrombotic treatment in cervical artery dissection – Design of the TREAT-CAD randomised trial. Eur Stroke J 2020; 5(3): 309-19.
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7. Yaghi S, Shu L, Mandel D, et al. Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study. Stroke 2024; 55(4): 908-18.
8. Yaghi S, Shu L, Fletcher L, et al. Anticoagulation Versus Antiplatelets in Spontaneous Cervical Artery Dissection: A Systematic Review and Meta-Analysis. Stroke 2024; 55(7): 1776-86.
9. Engelter ST, Enz LS, Ravanelli F, et al. The 6-months follow-up of the TREAT-CAD trial: Aspirin versus anticoagulation for stroke prevention in patients with cervical artery dissection. Eur Stroke J 2025: 23969873251315362.
10. Pezzini D, Grassi M, Zedde ML, et al. Antithrombotic therapy in the postacute phase of cervical artery dissection: the Italian Project on Stroke in Young Adults Cervical Artery Dissection. J Neurol Neurosurg Psychiatry 2022; 93(7): 686-92.