← Back

ATAMIS Post Hoc LAA

Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis: Post Hoc Analysis of ATAMIS

Share Share Copied! Compare

Year of Publication: 2024

Authors: Yu Cui, Quan-Ying Liu, Hui-Sheng Chen

Journal: Journal of the American Heart Association

Citation: Cui Y, Liu QY, Chen HS. J Am Heart Assoc. 2024;13:e036318.

Link: https://www.ahajournals.org/doi/full/10.1161/JAHA.124.036318

PDF: https://www.ahajournals.org/doi/epub/10.1161/JAHA.124.036318

Clinical Question

Does dual antiplatelet therapy (clopidogrel plus aspirin) reduce early neurologic deterioration in acute mild to moderate ischemic stroke patients with large-artery atherosclerosis compared to those without?

Bottom Line

Post hoc analysis of ATAMIS (2,910 patients): DAPT significantly reduced early neurologic deterioration (END) at 7 days in large-artery atherosclerosis (LAA) stroke (6.7% vs 17.0%; adjusted RD -10.4%; P=0.001), but not in non-LAA stroke (4.6% vs 5.9%; P=0.06). LAA patients had higher baseline END risk (11.6% vs 5.2%). Interaction P=0.11 (NS). LAA vs SAO interaction was significant (P=0.02). Supports precision antiplatelet therapy guided by TOAST subtyping.

        Major Points
        DAPT reduced END in LAA stroke: 6.7% vs 17.0% (adjusted RD -10.4%; P=0.001). Not in non-LAA: -1.4% (P=0.06).
LAA has higher baseline END risk: 11.6% vs 5.2% (P=0.001) regardless of treatment.
Interaction P=0.11 (NS) — hypothesis-generating; but LAA vs SAO interaction P=0.02 (significant).
SAO subtype showed no DAPT benefit: RD +1.6% (P=0.17) — mechanistically distinct from LAA.
No safety concern: bleeding 1.7% vs 1.9% (LAA); 0.6% vs 0.9% (non-LAA). No ICH in LAA group.
Sensitivity analyses robust: per-protocol RD -10.0% (P=0.001); propensity-matched RD -9.4% (P=0.03).
No functional outcome benefit: mRS 0-1 at 90 days 67.9% vs 61.3% (LAA; P=0.14).
Time window: significant interaction at 24-48h (P=0.046) — supports extended DAPT window for LAA.
2,910 patients from ATAMIS (NIHSS 4-10). LAA=225 (7.7%). Chinese population.
Supports TOAST subtyping to guide DAPT: LAA patients warrant DAPT even in mild-moderate stroke.

      

Design

Study Type: Multicenter, randomized, open-label, blinded-endpoint trial

Randomization: 1

Blinding: Blinded endpoint

Enrollment Period: Not reported in post hoc paper

Follow-up Duration: 90 days

Countries: China

Sample Size: 2910

Analysis: Modified intention-to-treat; adjusted and sensitivity analyses using generalized linear models, Cox regression, and propensity score matching

Inclusion Criteria

Age ≥18 years
Modified Rankin Scale ≤1 before stroke
Acute ischemic stroke within 48 hours
NIHSS score 4–10

Exclusion Criteria

Eligibility for intravenous thrombolysis or endovascular therapy
Clear indication for anticoagulation
History of intracerebral hemorrhage

Baseline Characteristics

Characteristic	Control	Active
Mean Age	67 (61–74)	65 (57–73)
Sex - Female	40.6%	31.9%
SBP	155 (140–170)	158 (141–169)
DBP	90 (80–97)	90 (84–100)
Hypertension	66.0%	67.2%
Diabetes	24.5%	29.4%
Prior Stroke	38.7%	40.3%
TIA	0.9%	1.7%
Smoker	36.8%	39.8%

Arms

Field	Clopidogrel plus Aspirin	Control
Intervention	Clopidogrel plus aspirin initiated within 48h of stroke onset	Aspirin monotherapy
Duration	7 days primary treatment, follow-up to 90 days	7 days primary treatment, follow-up to 90 days

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Early neurologic deterioration at 7 days (>2-point increase in NIHSS not due to hemorrhage)	Primary	17.0% (LAA subgroup)	6.7% (LAA subgroup)	10.30%	0.001
mRS 0–1 at 90 days (LAA)	Secondary	61.3%	67.9%		0.14
New stroke within 90 days (LAA)	Secondary	2.2%	1.8%	0.68	0.71
Any Bleeding	Adverse	1.9%	1.7%		0.65
Intracranial Hemorrhage	Adverse	0%	0%		NA

Subgroup Analysis

Significant interaction in 24–48h treatment window (P=0.046), favoring DAPT in LAA subtype. No interaction in 0–24h group. Sensitivity analyses consistent with primary findings.

Criticisms

Post hoc design limits causal inference.
Small LAA subgroup compared to non-LAA may affect statistical power.
Findings limited to Chinese population.
Stroke subtype classification dependent on vessel imaging, which was not uniformly available.

Funding

Science and Technology Project Plan of Liaoning Province (2019JH2/10300027)

Based on: ATAMIS Post Hoc LAA (Journal of the American Heart Association, 2024)

Authors: Yu Cui, Quan-Ying Liu, Hui-Sheng Chen

Citation: Cui Y, Liu QY, Chen HS. J Am Heart Assoc. 2024;13:e036318.

Content summarized and formatted by NeuroTrials.ai.

ATAMIS Post Hoc LAA

(2024)

Objective

To evaluate whether dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin is more effective than aspirin alone in patients with NIHSS4-10 caused by large-artery atherosclerosis (LAA).

Study Summary

• Post hoc analysis of ATAMIS focused on LAA vs non-LAA stroke subtypes. • DAPT was associated with reduced early neurologic deterioration (END) at 7 days in LAA patients but No significant benefit observed in non-LAA subgroup.

Intervention

Clopidogrel 75 mg daily + aspirin 100 mg daily vs aspirin 100 mg daily alone; initiated within 48 hours of stroke onset.

Study Design

Arms: Array

Outcome

• END at 7 days: 6.7% in DAPT vs 17.0% in aspirin in LAA (adjusted risk difference −10.4%, p=0.001). • END in non-LAA: 4.6% in DAPT vs 5.9% in aspirin (p=0.06). • No significant difference in bleeding or functional outcomes at 90 days between groups. • Sensitivity analysis confirmed robustness of results, especially in LAA subgroup.

Bottom Line

Major Points

DAPT reduced END in LAA stroke: 6.7% vs 17.0% (adjusted RD -10.4%; P=0.001). Not in non-LAA: -1.4% (P=0.06).
LAA has higher baseline END risk: 11.6% vs 5.2% (P=0.001) regardless of treatment.
Interaction P=0.11 (NS) — hypothesis-generating; but LAA vs SAO interaction P=0.02 (significant).
SAO subtype showed no DAPT benefit: RD +1.6% (P=0.17) — mechanistically distinct from LAA.
No safety concern: bleeding 1.7% vs 1.9% (LAA); 0.6% vs 0.9% (non-LAA). No ICH in LAA group.
Sensitivity analyses robust: per-protocol RD -10.0% (P=0.001); propensity-matched RD -9.4% (P=0.03).
No functional outcome benefit: mRS 0-1 at 90 days 67.9% vs 61.3% (LAA; P=0.14).
Time window: significant interaction at 24-48h (P=0.046) — supports extended DAPT window for LAA.
2,910 patients from ATAMIS (NIHSS 4-10). LAA=225 (7.7%). Chinese population.
Supports TOAST subtyping to guide DAPT: LAA patients warrant DAPT even in mild-moderate stroke.

Study Design

Study Type: Multicenter, randomized, open-label, blinded-endpoint trial
Randomization: Yes
Blinding: Blinded endpoint
Sample Size: 2910
Follow-up: 90 days
Countries: China

Primary Outcome

Definition: Early neurologic deterioration at 7 days (>2-point increase in NIHSS not due to hemorrhage)

Control	Intervention	HR/OR	P-value
17.0% (LAA subgroup)	6.7% (LAA subgroup)	- (−16.2% to −4.7%)	0.001

Limitations & Criticisms

Post hoc design limits causal inference.
Small LAA subgroup compared to non-LAA may affect statistical power.
Findings limited to Chinese population.
Stroke subtype classification dependent on vessel imaging, which was not uniformly available.

Citation

Cui Y, Liu QY, Chen HS. J Am Heart Assoc. 2024;13:e036318.

View Original Publication →

ATAMIS Post Hoc LAA

Dual Antiplatelet Therapy and Outcomes in Acute Mild to Moderate Stroke With Versus Without Large-Artery Atherosclerosis: Post Hoc Analysis of ATAMIS

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

Ask about ATAMIS Post Hoc LAA