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ARAMIS Post hoc (LVO)

Dual Antiplatelet Versus Alteplase for Early Neurologic Deterioration in Minor Stroke With Versus Without Large Vessel Occlusion: Prespecified Post Hoc Analysis of the ARAMIS Trial

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Year of Publication: 2024

Authors: Yu Cui, Chao He, Zi-Ang Li, ..., Hui-Sheng Chen

Journal: Stroke

Citation: Stroke. 2024;55:2590–2598

Clinical Question

Is dual antiplatelet therapy more effective than intravenous alteplase in preventing early neurological deterioration in minor strokes without large vessel occlusion compared to those with large vessel occlusion?

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%, P<0.001)
  • No significant difference in END between treatments in LVO group (15.4% vs 13.0%; adjusted RD 2.3%, P=0.82)
  • Marginally significant interaction between treatment effects and LVO status (P=0.06)
  • DAPT associated with significantly fewer bleeding events than alteplase in non-LVO group (0.5% vs 7.7%, P<0.001)

Design

Study Type: Prespecified post hoc analysis of randomized controlled trial

Randomization: 1

Blinding: Open-label with blinded outcome assessment for mRS and vascular events at 90 days

Follow-up Duration: 90 days

Countries: China

Sample Size: 480

Analysis: As-treated analysis; generalized linear models with binomial distribution and identity link function; adjusted for baseline imbalances; IBM SPSS 26.0 and R 4.1.0

Inclusion Criteria

  • Patients from ARAMIS trial as-treated analysis set
  • Age ≥18 years
  • Acute ischemic stroke with NIHSS ≤5 (minor) and nondisabling neurological deficit
  • Symptom onset within 4.5 hours
  • Responsible vessel examination available (CT angiography or MR angiography)

Exclusion Criteria

  • mRS scores before stroke ≥2
  • Definite indication for anticoagulation
  • History of intracerebral hemorrhage
  • No cerebral vessel examination available

Arms

FieldDAPTControl
InterventionClopidogrel 300 mg loading dose on day 1 followed by 75 mg daily for 12±2 days plus aspirin 100 mg daily for 12±2 days, then single or dual antiplatelets per guidelines until 90 daysIntravenous alteplase 0.9 mg/kg (maximum 90 mg) followed by guideline-based antiplatelet treatment starting 24 hours post-thrombolysis (DAPT for 12±2 days consistent with DAPT group)
Duration12±2 days initial DAPT, then guideline-based therapy to 90 daysSingle dose alteplase, then antiplatelet therapy

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Early neurological deterioration (END) at 24 hours defined as ≥4-point NIHSS score increase compared with baselinePrimaryLVO: 13.0%, Non-LVO: 5.7%LVO: 15.4%, Non-LVO: 0.5%LVO: 0.82, Non-LVO: <0.001
Excellent functional outcome at 90 days (mRS 0-1)SecondaryLVO: 87.0%, Non-LVO: 92.7%LVO: 92.3%, Non-LVO: 94.9%LVO: 0.29, Non-LVO: 0.43
Favorable functional outcome at 90 days (mRS 0-2)SecondaryLVO: 91.3%, Non-LVO: 96.3%LVO: 92.3%, Non-LVO: 96.9%LVO: 0.46, Non-LVO: 0.80
Early neurological improvement at 24 hours (≥2-point NIHSS decrease)SecondaryLVO: 17.4%, Non-LVO: 19.4%LVO: 7.7%, Non-LVO: 13.2%LVO: 0.46, Non-LVO: 0.85
Symptomatic intracranial hemorrhageAdverseLVO: 0%, Non-LVO: 0.8%LVO: 0%, Non-LVO: 0%LVO: NA, Non-LVO: 0.25
Bleeding eventsAdverseLVO: 0%, Non-LVO: 7.7%LVO: 0%, Non-LVO: 0.5%LVO: NA, Non-LVO: <0.001
All-cause mortality at 90 daysAdverseLVO: 0%, Non-LVO: 0%LVO: 0%, Non-LVO: 0.5%LVO: NA, Non-LVO: 0.47

Subgroup Analysis

No significant interaction between treatment effects and groups regarding primary outcome in prespecified subgroup analysis by age, sex, history of diabetes, NIHSS score, time from onset to treatment, and location of responsible vessel

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

Funding

Science and Technology Project Plan of Liaoning Province (2022JH2/101500020); funders had no role in study design, data collection, analysis, or interpretation

Based on: ARAMIS Post hoc (LVO) (Stroke, 2024)

Authors: Yu Cui, Chao He, Zi-Ang Li, ..., Hui-Sheng Chen

Citation: Stroke. 2024;55:2590–2598

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