TREAT-CAD 6-months
The 6-months follow-up of the TREAT-CAD trial: Aspirin versus anticoagulation for stroke prevention in patients with cervical artery dissection
Year of Publication: 2025
Authors: Stefan T Engelter, Lukas S Enz, Flavia Ravanelli, ..., and Christopher Traenka
Journal: European Stroke Journal
Citation: European Stroke Journal 1–11. DOI: 10.1177/23969873251315362
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC11803590/
PDF: https://pmc.ncbi.nlm.nih.gov/articles/PM...73251315362.pdf
PDF: Clinical Question
What are the new clinical (ischemic stroke, intracranial/major extracranial bleeding, or death) and new MR-Imaging outcomes (ischemic or hemorrhagic brain lesions) between 3 and 6 months in patients with symptomatic, MR-imaging-verified cervical artery dissection treated with aspirin versus anticoagulation?
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).
Design
Study Type: Randomized controlled trial with blinded outcome assessment (extended follow-up of original trial)
Randomization: 1
Blinding: Blinded MRI and outcome adjudication; treating clinicians and adjudication committee not blinded
Enrollment Period: Original trial first patient inclusion: October 3, 2013
Follow-up Duration: 3 to 6 months (extended follow-up from 3-month trial endpoint)
Countries: Switzerland, Germany, Denmark
Sample Size: 122
Analysis: As-treated primary analysis; Wilson’s method for CI; R statistical software; sensitivity analysis by original randomization
Inclusion Criteria
- MR-verified clinically symptomatic cervical artery dissection
- Adherence to allocated study medication for 3 months
- Completed the 3-month assessment
- Consent for extended follow-up including 6-month clinical and MRI assessment
Exclusion Criteria
- Switched to non-protocol antithrombotics (e.g., DOACs or clopidogrel) between 3 and 6 months
- Unknown treatment type between 3 and 6 months
- Declined participation in 6-month follow-up
Baseline Characteristics
| Characteristic | Control | Active |
|---|---|---|
| Age (years, mean (SD)) | 51 (12.1) | 45.3 (10.4) |
| Male sex, n (%) | 21 (72.4) | 59 (63.4) |
| Site of dissection - Internal Carotid Artery, n (%) | 16 (55.2) | 65 (69.9) |
| Site of dissection - Vertebral Artery, n (%) | 13 (44.8) | 29 (31.2) |
| Multivessel dissection, n (%) | 2 (6.9) | 3 (3.2) |
| Occlusion of dissected artery, n (%) | 11 (37.9) | 29 (31.2) |
| Mural hematoma, n (%) | 28 (96.6) | 90 (96.8) |
| Ischemic stroke | 12 (41.4) | 47 (50.5) |
| Transient ischemic attack | 4 (13.8) | 11 (11.8) |
| Retinal infarct | 0 (0) | 4 (4.3) |
| Amaurosis fugax | 2 (6.9) | 1 (1.1) |
| Cervical pain | 15 (51.7) | 48 (51.6) |
| Headache | 21 (72.4) | 63 (67.7) |
| Cranial nerve palsy | 2 (6.9) | 12 (12.9) |
| Horner's syndrome | 11 (37.9) | 35 (37.6) |
| Tinnitus | 0 (0) | 13 (14) |
| NIHSS score baseline, mean (SD) | 1.2 (2.4) | 1.1 (2.4) |
| Hypertension | 16 (55.2) | 30 (32.3) |
| Hypercholesterolemia | 7 (24.1) | 16 (17.2) |
| Diabetes | 2 (6.9) | 1 (1.1) |
| History of smoking | 18 (62.1) | 51 (54.8) |
| Migraine with aura | 2 (6.9) | 15 (16.1) |
| Migraine without aura | 3 (10.3) | 13 (14) |
| Mechanical trigger event | 6 (20.7) | 14 (15.1) |
| Infection prior to enrollment | 5 (17.2) | 27 (29) |
Arms
| Field | Aspirin (as-treated) | Control |
|---|---|---|
| Intervention | Aspirin (75 mg or 100 mg daily) from 3 to 6 months after index event | Anticoagulation with phenprocoumon, acenocoumarol, or warfarin from 3 to 6 months after index event |
| Duration | 3 to 6 months | 3 to 6 months |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| 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 | Primary | 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 | 0.22% | 1.0 |
| Major clinical extracranial hemorrhage | Adverse | 0 | 1 | ||
| New hemorrhagic MR lesion | Adverse | 1 | 2 |
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
Subgroup Analysis
A sensitivity analysis using per-protocol allocation (original randomization) confirmed similar findings. No statistically significant differences in outcomes were found between groups.
Funding
Swiss National Science Foundation (grant 140340), Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel, and the Science Fund Rehabilitation of the University Department of Geriatric Medicine Felix Platter Basel.
Based on: TREAT-CAD 6-months (European Stroke Journal, 2025)
Authors: Stefan T Engelter, Lukas S Enz, Flavia Ravanelli, ..., and Christopher Traenka
Citation: European Stroke Journal 1–11. DOI: 10.1177/23969873251315362
Content summarized and formatted by NeuroTrials.ai.