Platelet Function During Extended Prasugrel and Clopidogrel Therapy for Patients With ACS Treated Without Revascularization: The TRILOGY ACS Platelet Function Substudy

Study Questions:

What are the differences in clinical outcomes and platelet reactivity in patients with acute coronary syndrome (ACS) treated with prasugrel versus clopidogrel?

Methods:

A total of 9,326 patients with medically managed ACS were randomized to receive prasugrel (10 or 5 mg/d) or clopidogrel (75 mg/ d). Platelet reactivity, measured in P2Y12 reaction units (PRUs), was performed at baseline and multiple time points after randomization. The primary efficacy endpoint was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke.

Results:

Median PRU values were significantly lower in the prasugrel group compared to the clopidogrel group (p < 0.001) throughout the trial. At 30 months, the rate of the primary efficacy endpoint was 17.2% (160 events) in the prasugrel group versus 18.9% (180 events) in the clopidogrel group (p = 0.29). There were no significant differences in the continuous distributions of 30-day PRU values for participants with a primary efficacy endpoint event after 30 days (n = 214) compared with participants without an event (n = 1,794; p = 0.07), and no significant relationship between the occurrence of the primary efficacy endpoint and continuous PRU values.

Conclusions:

Among patients with ACS managed medically, prasugrel was associated with lower platelet reactivity than clopidogrel. No significant differences existed between prasugrel versus clopidogrel in the occurrence of the primary efficacy endpoint through 30 months, and no significant association existed between platelet reactivity and occurrence of ischemic outcomes.

Perspective:

The TRILOGY ACS study demonstrated that in ACS patients managed medically, there is no significant difference in clinical outcomes when comparing patients treated with prasugrel or clopidogrel. This platelet substudy demonstrates that although prasugrel at 5 or 10 mg/d was effective in lowering platelet reactivity more than clopidogrel, there was no associated improvement in outcomes. Importantly, this study demonstrated there was no association between platelet reactivity and CV events in patients treated with dual antiplatelet therapy, questioning the clinical utility of platelet reactivity measurements in this group of patients.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, ACS and Cardiac Biomarkers, Interventions and ACS, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging

Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Biological Markers, Coronary Angiography, Platelet Function Tests, Tomography, X-Ray Computed, Thiophenes, Ticlopidine, Piperazines, Blood Platelets, Platelet Activation


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