ARAMIS Trial: Dual Antiplatelet Therapy vs Alteplase for Minor Nondisabling Stroke
In patients with minor nondisabling acute ischemic stroke within 4.5 hours, is dual antiplatelet therapy (clopidogrel plus aspirin) non-inferior to IV alteplase for excellent functional outcome (mRS 0-1) at 90 days?
Chen HS, et al. (JAMA 2023) · 760 patients
Population
Included
- Acute minor nondisabling ischemic stroke (not causing significant disability)
- NIHSS ≤5 at presentation
- Treatable within 4.5 hours of onset
- Age 18 or older
- Age 18 years or older
- Acute ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less
- No more than 1 point on any single-item NIHSS score (such as vision, language, neglect, or single-limb weakness)
- A score of 0 on the consciousness item of the NIHSS at the time of randomization
- Computed tomography or magnetic resonance imaging performed on admission to identify ischemic stroke
- Able to start study treatment within 4.5 hours of stroke symptom onset
- Nondisabling deficit, adjudicated by trained investigators in consultation with the patient and available family based on the patient career and hobbies to judge whether the neurologic deficit would affect activities of daily living and work
Excluded
- Disabling stroke (significant functional impairment)
- Prior use of antiplatelet or anticoagulant therapy
- Contraindication to clopidogrel or aspirin
- Planned IV alteplase treatment
- Prestroke disability (modified Rankin Scale score of 2 or higher)
- History of intracerebral hemorrhage
- A definite indication for anticoagulation
Source: Chen HS et al., JAMA 2023;329(24):2135-2144· Retrieved 2026-06-09
Primary Outcome
Small absolute difference — interpret with caution
mRS 0-1 at 90 Days
Study Arms
- Agent
- Clopidogrel plus aspirin (dual antiplatelet therapy, DAPT)
- Dose
- Clopidogrel 300 mg loading on day 1, then 75 mg daily for 12 (plus or minus 2) days; aspirin 100 mg on day 1, then 100 mg daily for 12 (plus or minus 2) days
- Route
- Oral
- Frequency
- Once daily after the day-1 clopidogrel loading dose
- Duration
- Short-course DAPT for 12 (plus or minus 2) days, then guideline-based antiplatelet treatment until 90 days
- Co-interventions
- After the 12 (plus or minus 2) day DAPT course, single antiplatelet therapy or DAPT was continued per guidelines until 90 days.
Experimental arm tested for noninferiority to alteplase (n=393 randomized, 369 in full analysis set). Regimen verbatim from Chen JAMA 2023 p.2135 (abstract) and p.2137 (Procedures). The 12-day DAPT duration was based on the CHANCE time-course analysis. Open-label, blinded-endpoint multicenter trial at 38 hospitals in China. ClinicalTrials.gov NCT03661411.
- Agent
- Alteplase (intravenous recombinant tissue plasminogen activator)
- Dose
- 0.9 mg/kg (maximum 90 mg)
- Route
- Intravenous
- Frequency
- 10% as a bolus, then 90% infused over 1 hour
- Duration
- About 60 minutes
- Co-interventions
- Guideline-based antiplatelet treatment began 24 hours after receipt of alteplase.
Active comparator representing the guideline standard of care being tested against (n=367 randomized, 350 in full analysis set). Dose and administration verbatim from Chen JAMA 2023 p.2135 (abstract) and p.2136-2137 (Procedures). High crossover (20.4%) was a noted limitation; noninferiority held across full analysis, per-protocol, and as-treated populations.
Safety
Symptomatic intracranial hemorrhage at 24 hours
0.3%
0.9%
sICH was numerically lower with DAPT (0.3% vs 0.9%), consistent with an antithrombotic approach without plasminogen activation.
Trial Design
Type
- Multicenter, open-label, blinded-endpoint randomized noninferiority trial
- Minor nondisabling acute ischemic stroke within 4.5 hours
- DAPT vs IV alteplase
Timeline
China; October 2018 to April 2022
N
760
Enrollment
760 patients at 28 centers in China. Open-label blinded-endpoint NI RCT. October 2018 to April 2022. Published JAMA 2023.
ClinicalTrials.gov
NCT03661411Bedside Pearl
ARAMIS showed DAPT is non-inferior to alteplase for minor nondisabling stroke (NNT context: both arms excellent, 93.8% vs 91.4%). The key bedside application: for clearly minor, nondisabling deficits within 4.5 hours, DAPT is a reasonable alternative that avoids the 0.9% sICH risk of alteplase. Do not apply to disabling stroke.
See also