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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

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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%, 95% CI -16.2% to -4.7%; P=0.001), but not in non-LAA stroke (4.6% vs 5.9%; adjusted RD -1.4%; P=0.06). LAA patients had higher baseline END risk (11.6% vs 5.2%). Overall 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.
  • Overall interaction P=0.11 (NS) — hypothesis-generating; 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 2/119 (1.7%) vs 2/106 (1.9%) in LAA; 0/119 vs 0/106 ICH in LAA.
  • Sensitivity analyses robust: per-protocol adjusted 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: interaction P=0.046 in the 24–48h stratum, but no significant within-stratum difference between antiplatelet treatments in either 0–24h or 24–48h subgroup — hypothesis-generating.
  • 2,910 patients from ATAMIS (NIHSS 4-10). LAA=225 (7.7%). Chinese population.
  • Supports TOAST subtyping to guide DAPT: LAA patients may warrant DAPT even in mild-moderate stroke.

Design

Study Type: Post hoc analysis of ATAMIS, a multicenter, open-label, blinded–endpoint, randomized clinical 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

CharacteristicControlActive
Median Age67 (61–74)65 (57–73)
Sex - Female40.6%31.9%
SBP155 (140–170)158 (141–169)
DBP90 (80–97)90 (84–100)
Hypertension66.0%67.2%
Diabetes24.5%29.4%
Prior Stroke38.7%40.3%
TIA0.9%1.7%
Smoker36.8%39.8%
Baseline NIHSS5 (4–7)5 (4–7)

Arms

FieldClopidogrel plus AspirinControl
InterventionClopidogrel plus aspirin initiated within 48h of stroke onset (doses not specified in this post hoc paper)Aspirin monotherapy initiated within 48h of stroke onset (dose not specified in this post hoc paper)
DurationPrimary outcome assessed at 7 days; follow-up to 90 days (treatment duration not stated in this paper)Primary outcome assessed at 7 days; follow-up to 90 days (treatment duration not stated in this paper)

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Early neurologic deterioration at 7 days (>2-point increase in NIHSS not due to cerebral hemorrhage) — LAA subgroupPrimary18/106 (17.0%)8/119 (6.7%)10.30% (unadjusted RD -10.3%, 95% CI -18.7 to -1.8, P=0.02)0.001
mRS 0–1 at 90 days (LAA)Secondary57/93 (61.3%)76/112 (67.9%)0.14
mRS shift at 90 days (LAA)SecondaryNANA0.26
Change in NIHSS at 14 days (LAA)Secondary-0.51 (-0.92 to -0.05)-0.51 (-0.92 to -0.22)0.05
New stroke within 90 days (LAA)Secondary2/93 (2.2%)2/112 (1.8%)0.68 (0.09 to 5.12)0.71
Other vascular events or all-cause death within 90 days (LAA)Secondary2/93 (2.2%)1/112 (0.9%)0.12 (0.00 to 4.07)0.24
Any BleedingAdverse2/106 (1.9%)2/119 (1.7%)0.65
Intracranial HemorrhageAdverse0/106 (0.0%)0/119 (0.0%)NA

Subgroup Analysis

Significant interaction between stroke subtype and treatment effect within the 24–48h onset-to-treatment stratum (P=0.046); however, no significant within-subgroup difference between antiplatelet treatments was identified in either the 0–24h or the 24–48h LAA subgroup (small sample sizes after stratification). No interaction in the 0–24h stratum (P=0.33). Sensitivity analyses (per-protocol, propensity score matching, LAA vs SAO) consistent with primary findings. Findings hypothesis-generating; subgroup analysis was not powered and had no prespecified correction for multiple comparisons.

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.
  • Subgroup analyses not powered and lacked prespecified correction for multiple comparisons.

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.

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