Switching Acute Coronary Syndrome Patients From Prasugrel to Clopidogrel

Study Questions:

What is the impact of switching prasugrel to clopidogrel on platelet inhibition and clinical outcomes after an acute coronary syndrome (ACS)?


Platelet reactivity was measured with the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) in 300 ACS patients treated for 15 days with prasugrel 10 mg. Patients displaying low on-treatment platelet reactivity (LPR) or at high risk of bleeding were switched to clopidogrel 75 mg and tested again 15 days later. The rate of patients with high on-treatment platelet reactivity (HPR) defined as P2Y12 reaction units (PRUs) >208, and LPR (defined as PRU <30) were evaluated before and after the switch.


Among patients on prasugrel, the rate of LPR was 45.6% (n = 137), whereas 4.3% (n = 13) had HPR. A group of 31 patients (10.3%) was switched to clopidogrel 75 mg, of whom 29 had LPR (93.5%) on a regimen of prasugrel. On-treatment platelet reactivity (PRU) increased from 14 ± 4 on a regimen of prasugrel to 155 ± 15 on a regimen of clopidogrel (p < 0.0001), resulting in a much lower rate of patients with LPR (9.7%). The rate of patients with HPR increased from 0% with prasugrel to 29% (n = 9) with clopidogrel. The rate of minor bleeding decreased after the switch from 32% to 9.7% (p = 0.03).


The authors concluded that early switching from prasugrel 10 mg to clopidogrel 75 mg reduces the number of patients with LPR and minor bleeding events, but also unmasks a group of nonresponders to clopidogrel.


This study adds to the growing data suggesting that use of platelet aggregation studies to guide antiplatelet therapy is not ready for prime time. It is clear that patients with low platelet reactivity have more bleeding events and there appears to be an association between high platelet reactivity and ischemic events, but there are no data suggesting that modifying therapy in response to platelet function studies has any impact on clinical outcomes.

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

Keywords: Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Coronary Angiography, Platelet Function Tests, Platelet Aggregation, Thiophenes, Piperazines, Platelet Activation, Angioplasty, Balloon, Coronary, Hemorrhage

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