Key result
Prasugrel reloading did not significantly increase the proportion of patients achieving platelet reactivity <40 AUC at 4 hours compared to clopidogrel reloading (100% vs 91%, p=0.49).
Why the study?
Does prasugrel reloading improve platelet reactivity compared to clopidogrel reloading in ACS patients with high residual platelet reactivity on clopidogrel undergoing PCI?
RCT (n=44)
Open-label
Randomised
Yes
Does prasugrel reloading improve platelet reactivity compared to clopidogrel reloading in ACS patients with high residual platelet reactivity on clopidogrel undergoing PCI?
Absolute Event Rate: 100% vs 91%
p-value: p=0.49
In ACS patients with high residual platelet reactivity on clopidogrel, reloading with prasugrel provides faster and more sustained platelet inhibition compared to high-dose clopidogrel reloading, though the study was underpowered for the 4-hour primary endpoint.
Prasugrel reloading may yield faster platelet suppression than clopidogrel in poor responders; leaves open whether this improves clinical outcomes.
BACKGROUND: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. OBJECTIVES: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). PATIENTS: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. "poor responders" were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. RESULTS: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. CONCLUSIONS: Routine platelet function testing identifies patients with high residual platelet reactivity ("poor responders") on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT01339026.
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Geisler et al. (2015) conducted an RCT in Acute Coronary Syndromes with high platelet reactivity on clopidogrel (n=44). Prasugrel vs. Clopidogrel (600 mg reloading and 150 mg maintenance dose) was evaluated on Proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication (p=0.49). Prasugrel reloading did not significantly increase the proportion of patients achieving platelet reactivity <40 AUC at 4 hours compared to clopidogrel reloading (100% vs 91%, p=0.49).
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