PDF: ATAMIS
(2024)Objective
To evaluate whether dual antiplatelet therapy (clopidogrel plus aspirin) is superior to aspirin alone among patients with mild to moderate acute ischemic stroke (NIHSS 4-10).
Study Summary
Intervention
Clopidogrel (300 mg loading then 75 mg daily) + Aspirin (100 mg daily) for 14 days, followed by monotherapy vs. Aspirin alone (100–300 mg for 14 days then 100 mg daily).
Study Design
Arms: Array
Outcome
Bottom Line
DAPT reduced early neurologic deterioration at 7 days (4.8% vs 6.7%; RD -1.9%; RR 0.71; 95% CI 0.53-0.96; P=0.03) in NIHSS 4-10 stroke. No significant bleeding increase (0.7% vs 1.0%). However, no improvement in 90-day functional outcome (mRS 0-1: 76.9% vs 74.6%; P=0.14). Benefit was time-sensitive: significant only within <24 hours (P interaction=0.01).
Major Points
- Primary endpoint met: END at 7 days 4.8% (DAPT) vs 6.7% (aspirin); RD -1.9%; RR 0.71 (0.53-0.96; P=0.03).
- Fills evidence gap: CHANCE/POINT targeted NIHSS ≤3; ATAMIS specifically studied NIHSS 4-10.
- No 90-day functional benefit: mRS 0-1 76.9% vs 74.6% (RD 2.4%; P=0.14). Short 14-day DAPT duration may explain.
- Time-sensitive: benefit only within <24h (RD -3.6%; P=0.01 interaction). No benefit at ≥24h (RD +0.6%).
- No bleeding increase: any bleeding 0.7% vs 1.0% (P=0.35); sICH 0.1% vs 0.1%. Lower than CHANCE (2.3%).
- Predominantly undetermined etiology (61%) and small vessel (30%). Large artery only 7.5-7.9%.
- NIHSS ≥7 subgroup showed larger benefit (RD -4.6%) though interaction NS (P=0.21).
- Open-label PROBE design with blinded endpoints at 66 Chinese hospitals.
- 14-day DAPT then aspirin monotherapy through Day 90. 2,915 patients (mITT).
- Novel primary endpoint (END at 7 days) vs traditional stroke recurrence — clinically meaningful but different from CHANCE/POINT.
Study Design
- Study Type
- Multicenter, randomized, open-label, blinded endpoint (PROBE) trial
- Randomization
- Yes
- Blinding
- Open-label; blinded endpoint assessors. Simple randomization via computer-generated sequence.
- Sample Size
- 2915
- Follow-up
- 90 days
- Centers
- 66
- Countries
- China
Primary Outcome
Definition: Early neurologic deterioration at 7 days (NIHSS increase ≥2 points from baseline, excluding hemorrhage/metabolic causes)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 95/1,413 (6.7%) | 72/1,502 (4.8%) | - (0.53-0.96) | 0.03 |
Limitations & Criticisms
- Sample size imbalance (1,541 vs 1,459) from simple randomization.
- Open-label PROBE design.
- 82.8% had NIHSS 4-5 (mild end) — limited power for moderate stroke subgroup.
- Excluded thrombolysis/EVT patients.
- 14-day DAPT only — shorter than CHANCE (21 days).
- Chinese population only.
- No 90-day functional benefit despite primary endpoint being met.
- Benefit only within <24h (P interaction=0.01).
Citation
JAMA Neurol. 2024;81(5):450-460.