PDF: TREAT-CAD 6-months
(2025)Objective
To evaluate the occurrence of clinical and MRI outcomes between 3 and 6 months after cervical artery dissection (CeAD) in patients treated with aspirin or vitamin K antagonists.
Study Summary
Intervention
Aspirin (100 mg daily or 75 mg in Copenhagen) vs. vitamin K antagonists (phenprocoumon, acenocoumarol, or warfarin); treatment given between months 3 to 6 after initial randomization in CeAD patients.
Study Design
Arms: Aspirin 100 mg daily (n=173 as-treated) vs Vitamin-K antagonists (n=148 as-treated)
Outcome
Bottom Line
Clinical and MRI outcomes between 3 and 6 months were rare and occurred at similar rates in both treatment arms. All events were hemorrhagic, with no ischemic strokes or deaths, suggesting the need to reassess the benefit of continued antithrombotic treatment beyond 3 months.
Major Points
- TREAT-CAD previously failed to establish non-inferiority of aspirin to anticoagulation at 3 months.
- This follow-up study included 122 participants (93 aspirin, 29 VKA) in an as-treated analysis.
- Between 3 and 6 months, 3.2% in the aspirin group and 3.4% in the VKA group had new outcome events, all hemorrhagic.
- No ischemic events or deaths occurred in either group during this extended follow-up.
- The absolute risk difference was 0.2% (95% CI −8.0% to 7.5%, p=1.0).
Study Design
- Study Type
- Randomized controlled trial with blinded outcome assessment (extended follow-up of original trial)
- Randomization
- Yes
- Blinding
- Blinded MRI and outcome adjudication; treating clinicians and adjudication committee not blinded
- Sample Size
- 122
- Follow-up
- 3 to 6 months (extended follow-up from 3-month trial endpoint)
- Countries
- Switzerland, Germany, Denmark
Primary Outcome
Definition: Composite of new clinical (ischemic stroke, major bleeding, or death) and new MR-imaging outcomes (ischemic or hemorrhagic brain lesions) between 3 and 6 months
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 1/29 (3.4%) had a new hemorrhagic MR lesion | 3/93 (3.2%) had events: 1 clinical extracranial hemorrhage and 2 hemorrhagic MR lesions | - (−8.0% to 7.5%) | 1.0 |
Limitations & Criticisms
- Small sample size limits statistical power for detecting group differences
- Significant treatment crossover, primarily from anticoagulation to aspirin
- Missing 6-month data in some participants may bias results
- No MRI at 3 months—DWI lesions may have faded, underdetecting ischemic events
- Some hemorrhagic MRI lesions may represent transformed ischemic lesions
- Clinical significance of asymptomatic MRI lesions is uncertain
- Lack of systematic recanalization data limits interpretation of outcomes
Citation
European Stroke Journal 1–11. DOI: 10.1177/23969873251315362