PDF: STOP-CAD
(2024)Objective
To compare anticoagulation versus antiplatelet therapy for secondary stroke prevention in patients with cervical artery dissection (CAD).
Study Summary
• There was a trend (not statistically significant) for less ischemic stroke (1.5% vs 3.3%) but more major hemorrhage (0.7% vs 0.5%) with anticoagulation compared with antiplatelet.
• If you plan on anticoagulation, consider switching to antiplatlet after 90-days to avoid risk of major bleeding
• Subgroup analysis shows benefit with anticoagulation in patients with *occlusive dissection*
Intervention
Multinational observational study of 3636 CAD patients, with comparative analysis of exclusive anticoagulation (n=402) vs antiplatelet (n=2453) therapy over 180 days. Additional 781 received both during follow-up.
Inclusion Criteria
• Adults with cervical artery dissection
• Received either antiplatelet or anticoagulation therapy (or both)
Study Design
Arms: Antiplatelet only vs Anticoagulation only
Patients per Arm: 2453 antiplatelet, 402 anticoagulation, 781 mixed
Outcome
• Major hemorrhage: 0.5% vs 0.7%, p=0.484
• Occlusive dissection subgroup: More benefit with anticoagulation HR 0.40 (95% CI 0.18–0.88)
Bottom Line
Although no statistically significant difference between anti platelet and anticoagulation, there was a trend for lower ischemic stroke in anticoagulation group. There was also a trend for more major bleeding with anticoagulation group. Subgroup analysis shows benefit with anticoagulation in patients with *occlusive dissection*. If anticoagulation is chosen, switching to antiplatelet therapy before 180 days may be reasonable to lower the risk of major bleeding. Large prospective studies are needed for validation.
Major Points
- The STOP-CAD study was a large multicenter observational retrospective international study involving 3636 patients with cervical artery dissection (CAD).
- It compared antiplatelet therapy (2453 patients) with anticoagulation (402 patients) for stroke prevention and major hemorrhage.
- By day 180, 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%) occurred.
- Anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke at 30 days (HR 0.71; P=0.145) and 180 days (HR 0.80; P=0.670) compared to antiplatelet therapy.
- In patients with occlusive dissection, anticoagulation showed a significantly lower ischemic stroke risk (adjusted HR 0.40; P_interaction=0.009).
- Anticoagulation was associated with a significantly higher risk of major hemorrhage by day 180 (adjusted HR 5.56; P=0.009), but not by day 30 (adjusted HR 1.39; P=0.637).
- The majority of ischemic strokes occurred within the first 30 days (87.0%).
Study Design
- Study Type
- Observational Retrospective International Study
- Randomization
- No
- Blinding
- Outcomes were abstracted from available medical records and reviewed by site principal investigators. Neurologists at the lead site reviewed imaging reports to confirm outcomes.
- Sample Size
- 3636
- Follow-up
- Up to 180 days
- Centers
- 63
- Countries
- Countries not explicitly listed, stated as 16 countries
Primary Outcome
Definition: Subsequent ischemic stroke during follow-up, defined as new or worsening neurological symptoms lasting for at least 24 hours or <24 hours but with imaging evidence of new or enlarging acute infarction and referable to the territory of the affected artery.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 3.3% (130 out of 162 total strokes) occurred on antiplatelet therapy | 1.5% (32 out of 162 total strokes) occurred on anticoagulation | 0.8 | 0.670 |
Limitations & Criticisms
- Retrospective and observational study design, potentially leading to confounding by indication and residual confounding.
- Lack of central and blinded outcome adjudication.
- Approximately 10% of patients were lost to follow-up after 30 days.
- Findings may not be generalizable to patients in community hospitals or moderate-/low-income countries due to a predominance of tertiary care centers in the study.
- Low number of major hemorrhagic events prevented reliable propensity score matching for this outcome.
- Heterogeneity in the dual antiplatelet therapy group, limiting generalizability to nonclopidogrel-based dual antiplatelet therapy.
- As-treated and crossover approach may have favored treatments started at a later time point.
- Did not analyze imaging data in detail or capture reasons for crossover for patients who switched treatment.
Citation
Stroke. 2024;55:908-918. DOI: 10.1161/STROKEAHA.123.045731