Early Neurologic Deterioration and Efficacy of Dual Antiplatelet in Anterior Versus Posterior Circulation Stroke

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Acute mild-to-moderate ischemic stroke (anterior vs posterior circulation) (n=2431). Intervention: Clopidogrel plus aspirin vs. Aspirin alone. Primary outcome: Early neurologic deterioration (END) at 7 days (≥2-point increase in NIHSS score compared with baseline, excluding cerebral hemorrhage) in anterior circulation stroke (ARR -2.4%, 95% CI -4.1% to -0.8%, p=0.004).

Q: What does this research mean for the field?

Dual antiplatelet therapy with clopidogrel plus aspirin reduces 7-day early neurologic deterioration compared with aspirin alone in acute anterior circulation stroke, but not in posterior circulation stroke. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Yu Cui; Yi‐Han Wang; Xiangru Kong; Dawei Chen

doi:10.1161/jaha.124.037268

January 23, 2025Journal of the American Heart AssociationOpen Access

Early Neurologic Deterioration and Efficacy of Dual Antiplatelet in Anterior Versus Posterior Circulation Stroke

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Key result

Dual antiplatelet therapy yields ~2.4-point lower early neurologic deterioration in anterior circulation stroke.

ARR -2.4%
95% CI -4.1% to -0.8%
P=0.004
n=2,431

Figures

Why the study?

Anterior circulation stroke differs from posterior circulation stroke, leading investigators to evaluate whether the risk of early neurologic deterioration and its response to dual antiplatelet therapy varies by stroke territory.

Does dual antiplatelet therapy with clopidogrel plus aspirin compared with aspirin alone reduce the risk of early neurologic deterioration at 7 days differently in patients with acute mild-to-moderate anterior circulation stroke versus posterior circulation stroke?

Key Points

To evaluate whether the incidence of early neurologic deterioration and treatment responses to clopidogrel plus aspirin versus aspirin alone differ between anterior and posterior circulation acute ischemic stroke.
Prespecified post hoc analysis of the randomized ATAMIS trial (NCT02869009) including 2431 patients with acute mild-to-moderate ischemic stroke (1780 anterior circulation, 651 posterior circulation).
Patients received clopidogrel plus aspirin (910 anterior, 371 posterior) or aspirin alone (870 anterior, 280 posterior).
The primary outcome was early neurologic deterioration at 7 days, defined as a ≥2-point increase in National Institutes of Health Stroke Scale score from baseline.
Early neurologic deterioration occurred in 6.8% of patients with anterior circulation stroke versus 3.8% with posterior circulation stroke (adjusted risk difference 3.3%, 95% CI 1.9% to 4.7%, adjusted P=0.001; unadjusted P=0.007).
Clopidogrel plus aspirin significantly lowered 7-day deterioration in anterior circulation stroke (5.6% versus 8.0%; risk difference −2.4%, 95% CI −4.1% to −0.8%, P=0.004), but showed no significant effect in posterior circulation stroke (3.5% versus 4.3%; risk difference −0.6%, 95% CI −2.7% to 1.5%, P=0.57; interaction P=0.69).
In anterior circulation stroke, dual therapy increased 90-day excellent functional outcome (modified Rankin Scale score 0 to 1 in 76.6% versus 71.9%; adjusted risk difference 4.7%, 95% CI 1.8% to 7.6%, adjusted P=0.002).

Study Design

Type

RCT (n=2,431)

Blinding

Open-label, blinded-endpoint

Randomization

Randomized treatment assignment

Multicenter

Yes

Structured PICO

Does dual antiplatelet therapy with clopidogrel plus aspirin compared with aspirin alone reduce the risk of early neurologic deterioration at 7 days differently in patients with acute mild-to-moderate anterior circulation stroke versus posterior circulation stroke?

P

Population

2,431 Chinese adults (median age 66 years, 35.1% female) with acute mild-to-moderate ischemic stroke (NIHSS 4-10) within 48 hours of onset (1,780 anterior circulation, 651 posterior circulation) not eligible for reperfusion therapy, followed for up to 90 days.

I

Intervention

Dual antiplatelet therapy with clopidogrel plus aspirin (n=1,281 total; 910 in ACS, 371 in PCS)

C

Comparator

Aspirin monotherapy (aspirin alone) (n=1,150 total; 870 in ACS, 280 in PCS)

O

Outcome

Occurrence of early neurologic deterioration (END) at 7 days, defined as a ≥2-point increase in National Institutes of Health Stroke Scale (NIHSS) score compared with baseline (excluding cerebral hemorrhage), assessed by the same assessor at admission and follow-up.hard clinical

Main Result

Absolute Risk Reduction: -2.4 (95% CI -4.1–-0.8)

Absolute Event Rate: 5.6% vs 8%

Absolute Risk Reduction: 2.4%

p-value: p=0.004

In patients with acute mild-to-moderate ischemic stroke presenting within 48 hours, early neurologic deterioration is more frequent in anterior circulation stroke, and dual antiplatelet therapy with clopidogrel plus aspirin is significantly more effective than aspirin alone at preventing early deterioration and improving 90-day functional outcomes in anterior circulation stroke, though no significant treatment-by-territory interaction was observed.

Limitations

Imbalanced sample sizes between stroke territories with a relatively lower proportion of patients with posterior circulation stroke
NIHSS score is less reliable for evaluating neurologic deficits in posterior circulation stroke, potentially underestimating END in this group
Did not explore specific risk factors associated with END in anterior and posterior circulation stroke
Excluded patients who received intravenous thrombolysis or endovascular therapy, limiting generalizability to patients receiving reperfusion treatments
Exploratory post hoc analysis in a Chinese population requiring external confirmation
Imbalanced sample sizes between stroke territories, with a relatively lower proportion of patients with posterior circulation stroke (PCS).
The NIHSS score is less reliable for evaluating neurologic deficits in patients with PCS, which may lead to underestimation of END in this population.
Did not explore the specific risk factors associated with END in ACS and PCS.
Excluded patients who received intravenous thrombolysis or endovascular therapy, limiting generalizability to patients receiving reperfusion treatments.
Explorative nature of the post hoc analysis and limited generalizability outside of China.

Implication

Supports dual antiplatelet therapy to prevent early deterioration in anterior circulation stroke; extends randomized evidence on territory-specific effects.

Abstract

Background Anterior circulation stroke (ACS) differs from posterior circulation stroke (PCS) in several aspects. We hypothesize that the risk of early neurologic deterioration (END) and its responses to clopidogrel plus aspirin versus aspirin alone may be different between stroke territories. Methods and Results This was a prespecified post hoc analysis of ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial and included patients with definite infarct location who were classified into ACS and PCS according to stroke territory. Primary outcome was occurrence of END at 7 days, defined as ≥2‐point increase in National Institutes of Health Stroke Scale score compared with baseline. We compared the treatment effects of clopidogrel plus aspirin versus aspirin alone in each stroke territory. From 3000 patients, 2431 eligible patients (1780 with ACS [910 assigned into clopidogrel plus aspirin and 870 assigned into aspirin alone] and 651 with PCS [371 assigned into clopidogrel plus aspirin and 280 assigned into aspirin alone]) were included. Median age was 66 years and 35.1% were women. The occurrence of END was higher in ACS than PCS (6.8% versus 3.8%, P =0.007). clopidogrel plus aspirin was associated with lower risk of END in ACS (risk difference [95% CI]: −2.4% [−4.1% to −0.8%], P =0.004), but not in PCS (risk difference [95% CI]: −0.6% [−2.7% to 1.5%], P =0.57). No significant interaction was found ( P =0.69). Conclusions Our study demonstrated END was higher in acute mild‐to‐moderate ischemic stroke with anterior circulation, who derived more benefit from clopidogrel plus aspirin than aspirin alone. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02869009.

Discussion

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Cite This Study

Cui et al. (2025) conducted an RCT in Acute mild-to-moderate ischemic stroke (anterior vs posterior circulation) (n=2,431). Clopidogrel plus aspirin vs. Aspirin alone was evaluated on Early neurologic deterioration (END) at 7 days (≥2-point increase in NIHSS score compared with baseline, excluding cerebral hemorrhage) in anterior circulation stroke (ARR -2.4%, 95% CI -4.1% to -0.8%, p=0.004). Clopidogrel plus aspirin reduced 7-day early neurologic deterioration compared with aspirin alone in anterior circulation stroke (5.6% vs 8.0%; RD -2.4%, P=0.004), but not in posterior stroke.

synapsesocial.com/papers/6a75a7ce12165deef3dd8c77 https://doi.org/10.1161/jaha.124.037268

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Early Neurologic Deterioration and Efficacy of Dual Antiplatelet in Anterior Versus Posterior Circulation Stroke

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Early Neurologic Deterioration and Efficacy of Dual Antiplatelet in Anterior Versus Posterior Circulation Stroke

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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