P2Y₁₂ Inhibitor Response By Patient Background Factors: An Exploratory Post Hoc Subgroup Analysis of the ACUTE-PRAS Study

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Acute atherothrombotic stroke or high-risk TIA (n=176). Intervention: Prasugrel vs. Clopidogrel. Primary outcome: Non-high platelet reactivity (non-HPR) at Day 5 in patients with ABCD-GENE score ≥ 10 (OR 2.73, 95% CI 0.90-8.30, p=0.076).

Q: What does this research mean for the field?

The antiplatelet effects of prasugrel and clopidogrel vary according to patient background factors. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Shigeru Fujimoto; Yasuyuki Iguchi; Hiroshi Yamagami; Masatoshi Koga; Ryo Itabashi; Yusuke Yakushiji; Kazuma Kowata; Naoto Kimura; Yuka Terasawa; Takahiro Shimizu; Yuichi Miyazaki; Koichi Oki; Osamu Masuo; Hideki Matsuoka; Kenji Fukuda; Toshihiro Ueda; Ryota Tanaka; Wataru Hashimoto; Satoru Abe; Go Kato; Taketoshi Furugori; Kazumi Kimura; on behalf of the ACUTE-PRAS Investigators

doi:10.5551/jat.66056

Key result

Prasugrel fails to significantly improve early platelet inhibition over clopidogrel despite favorable subgroup trends.

OR 2.73
95% CI 0.90-8.30
P=0.076
n=176

Figures

Why the study?

The variability of antiplatelet effects of prasugrel and clopidogrel according to patient background factors in acute atherothrombotic stroke or high-risk TIA was unclear.

Does prasugrel improve early platelet inhibition compared to clopidogrel across different patient background subgroups with acute atherothrombotic stroke or high-risk TIA?

Key Points

To determine whether the antiplatelet effects of prasugrel and clopidogrel differ across baseline clinical characteristics in patients with acute atherothrombotic stroke or high-risk transient ischemic attack.
A post hoc exploratory analysis of the multicenter, open-label, randomized controlled ACUTE-PRAS trial evaluated 176 patients (88 received prasugrel and 88 received clopidogrel) within 48 hours of symptom onset.
High platelet reactivity (defined as platelet reaction units [PRU] > 208) and absolute PRU were measured on Day 5 across strata including age, chronic kidney disease, stroke severity, and onset-to-treatment time.
When therapy started within 24 hours of stroke onset, prasugrel significantly reduced Day 5 PRU versus clopidogrel (adjusted mean difference, -34.9; 95% CI, -51.9 to -18.0; p < 0.001), but not when started after 24 hours (-29.6; 95% CI, -64.8 to 5.6; p = 0.099).
Prasugrel produced greater PRU reductions than clopidogrel in both mild stroke (adjusted mean difference, -32.6; 95% CI, -49.9 to -15.3; p < 0.001) and moderate stroke (-40.2; 95% CI, -79.2 to -1.1; p = 0.044).
PRU reduction favored prasugrel in patients without prior ischemic stroke (adjusted mean difference, -34.9; 95% CI, -51.5 to -18.3; p < 0.001), whereas patients with prior stroke showed no statistically significant difference (-15.4; 95% CI, -66.1 to 35.2; p = 0.548).

Study Design

Type

RCT (n=176)

Blinding

Open-label

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does prasugrel improve early platelet inhibition compared to clopidogrel across different patient background subgroups with acute atherothrombotic stroke or high-risk TIA?

P

Population

176 patients with acute atherothrombotic stroke or high-risk TIA, randomized to prasugrel or clopidogrel within 48 hours of symptom onset, evaluated for platelet reactivity at 5 days.

I

Intervention

Prasugrel (3.75 mg or 2.5 mg once daily without initial loading dose) plus aspirin for the first 21 days, continued up to 90 days.

C

Comparator

Clopidogrel (initial dose 300 mg or 75 mg, maintenance 75 mg or 50 mg once daily at physician discretion) plus aspirin for the first 21 days, continued up to 90 days.

O

Outcome

High platelet reactivity (HPR; defined as platelet reaction units [PRU] >208) and absolute PRU assessed on Day 5 after starting treatment.surrogate

Main Result

Odds Ratio: 2.73 (95% CI 0.9–8.3)

p-value: p=0.076

Prasugrel provides more potent early platelet inhibition than clopidogrel in acute stroke patients, particularly in high-risk subgroups such as those with CKD, advanced age, or metabolic comorbidities.

Limitations

Post hoc, exploratory analysis limited to hypothesis generation
Small sample sizes in subgroups leading to low reliability of inferential statistics
No adjustment for multiplicity
Applicability of the ABCD-GENE score to Japanese populations remains uncertain due to derivation from Western cohorts with higher obesity rates
HPR defined dichotomously, which can mask moderate but clinically relevant shifts in overall PRU distribution
Low reliability of inferential statistics due to small sample sizes in subgroups
Analyses were strictly exploratory and post hoc

Implication

May guide prasugrel preference for early inhibition in high-risk stroke subgroups; extends post hoc evidence for tailored antiplatelet strategies.

Abstract

AIM: To explore whether the antiplatelet effects of prasugrel and clopidogrel vary according to patient background factors in the ACUTE-PRAS study. METHODS: This was a post hoc, hypothesis-generating, exploratory analysis of the multicenter, open-label, randomized controlled ACUTE-PRAS study, in which 176 patients with acute atherothrombotic stroke or high-risk TIA received prasugrel or clopidogrel within 48 h of symptom onset. High platelet reactivity (HPR; platelet reaction units [PRU] ＞208) and absolute PRU were assessed on Day 5 in subgroups stratified by ABCD-GENE score, age, body mass index (BMI), chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, dyslipidemia, time from stroke onset to treatment, National Institutes of Health Stroke Scale (NIHSS) score, and prior ischemic stroke. CONCLUSIONS: Prasugrel provided favorable early platelet inhibition, particularly in subgroups characterized by advanced age, CKD, low BMI, metabolic comorbidities, or very early treatment start.

Discussion

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Cite This Study

Fujimoto et al. (2026) conducted an RCT in Acute atherothrombotic stroke or high-risk TIA (n=176). Prasugrel vs. Clopidogrel was evaluated on Non-high platelet reactivity (non-HPR) at Day 5 in patients with ABCD-GENE score ≥ 10 (OR 2.73, 95% CI 0.90-8.30, p=0.076). Prasugrel provided favorable early platelet inhibition compared to clopidogrel across most clinical subgroups, particularly in patients with advanced age, chronic kidney disease, low BMI, metabolic comorbidities, or very early treatment start.

synapsesocial.com/papers/69a91cbed6127c7a504bfaa9 https://doi.org/10.5551/jat.66056

Topics

Dual antiplatelet therapy

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P2Y₁₂ Inhibitor Response By Patient Background Factors: An Exploratory Post Hoc Subgroup Analysis of the ACUTE-PRAS Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

P2Y₁₂ Inhibitor Response By Patient Background Factors: An Exploratory Post Hoc Subgroup Analysis of the ACUTE-PRAS Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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