ARAMIS Post hoc (LVO)
(2024)Objective
To compare dual antiplatelet therapy (DAPT) versus alteplase for preventing early neurological deterioration in minor stroke patients with and without large vessel occlusion
Study Summary
• No significant difference in LVO group (15.4% vs 13.0%; adjusted RD 2.3%, P=0.82); interaction Pint=0.06
Intervention
Post hoc analysis of ARAMIS trial comparing DAPT (clopidogrel 300 mg loading then 75 mg daily + aspirin 100 mg daily for 12±2 days) versus intravenous alteplase (0.9 mg/kg, max 90 mg) in minor stroke patients stratified by LVO status
Inclusion Criteria
Age ≥18 years, acute ischemic stroke with NIHSS ≤5, nondisabling neurological deficit, symptom onset within 4.5 hours, cerebral vessel examination available
Study Design
Arms: DAPT (clopidogrel + aspirin for 12±2 days) vs Intravenous alteplase (0.9 mg/kg) followed by DAPT at 24h
Patients per Arm: LVO group: 13 DAPT, 23 alteplase; Non-LVO group: 197 DAPT, 247 alteplase
Outcome
• No difference in LVO group (adjusted RD 2.3%, 95% CI -17.6% to 22.3%, P=0.82)
• Bleeding events lower with DAPT in non-LVO group (0.5% vs 7.7%; adjusted RD -6.4%, P<0.001)
Bottom Line
Among minor nondisabling acute ischemic stroke patients without large vessel occlusion, DAPT may be superior to intravenous alteplase in preventing early neurological deterioration with a better safety profile, but this benefit was not seen in patients with large vessel occlusion.
Major Points
- Prespecified post hoc analysis of ARAMIS trial including 480 patients: 36 with LVO and 444 without LVO
- DAPT significantly reduced early neurological deterioration (END) compared to alteplase in non-LVO group (0.5% vs 5.7%; adjusted RD -4.8%, 95% CI -6.9% to -2.6%, P<0.001)
- No significant difference in END between treatments in LVO group (15.4% vs 13.0%; adjusted RD 2.3%, 95% CI -17.6% to 22.3%, P=0.82)
- Marginally significant interaction between treatment effects and LVO status (Pint=0.06)
- DAPT associated with significantly fewer bleeding events than alteplase in non-LVO group (0.5% vs 7.7%; adjusted RD -6.4%, 95% CI -8.9% to -3.9%, P<0.001)
Study Design
- Study Type
- Prespecified post hoc analysis of randomized controlled trial
- Randomization
- Yes
- Blinding
- Open-label; NIHSS at baseline/24 h assessed by unblinded investigators; 90-day mRS and vascular events assessed by blinded assessors
- Sample Size
- 480
- Follow-up
- 90 days
- Countries
- China
Primary Outcome
Definition: Early neurological deterioration (END) at 24 hours, defined as ≥4-point NIHSS score increase compared with baseline, but not as a result of cerebral hemorrhage
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| LVO: 3/23 (13.0%); Non-LVO: 14/247 (5.7%) | LVO: 2/13 (15.4%); Non-LVO: 1/197 (0.5%) | - (Adjusted RD — LVO: 2.3% (-17.6% to 22.3%); Non-LVO: -4.8% (-6.9% to -2.6%); Pint=0.06) | LVO: 0.82; Non-LVO: <0.001 |
Limitations & Criticisms
- Unbalanced sample size between groups, especially small LVO group (n=36) affecting statistical power
- 33.6% of patients excluded from as-treated analysis due to lack of vessel examination
- 20.4% crossover rate in original ARAMIS trial introduces potential selection bias
- Post hoc analysis nature limits strength of conclusions and requires confirmation
- NIHSS assessment at 24 hours not blinded to treatment allocation introducing potential observer bias
- Results may not be generalizable outside Chinese population
- Did not investigate degree of vessel stenosis after treatment to confirm mechanistic hypothesis
Citation
Stroke. 2024;55:2590–2598