Abstract
The prevalence of high platelet reactivity (HPR) in patients who have switched from clopidogrel to prasugrel during maintenance phase after an acute coronary syndrome (ACS) event is unknown. Therefore, the effect of switching from clopidogrel to prasugrel on the prevalence of HPR was evaluated. This analysis from the previously reported SWAP (SWitching Anti Platelet) study assessed HPR at baseline, 2 and 24 hours, and seven days after switching from clopidogrel to prasugrel maintenance dose (MD), with or without a prasugrel loading dose (LD) using four definitions: maximum platelet aggregation (MPA) >65% (primary endpoint), MPA >50%, P2Y12 reaction units (PRU) >235, and platelet reactivity index (PRI) ≥ 50%. A total of 95 patients were available for analysis; 56 patients provided DNA for genetic assessments of cytochrome P450 (CYP) 2C19. There were 26 (27.4%) patients with HPR at the end of the clopidogrel run-in (defined as MPA >65%). The HPR prevalence varied by each definition and ranged from 19% (PRU >235) to 68% (PRI ≥ 50 %). A significantly higher HPR prevalence was observed during clopidogrel versus the combined prasugrel therapy groups at seven days as measured by MPA >65% (21.2% vs. 4.5%, p<0.05), PRU >235 (18.8% vs. 0%, p=0.001), and PRI ≥ 50 % (66.7% vs. 7.9%, p<0.0001). There was a significantly higher percentage of subjects carrying at least one reduced function allele with HPR measured by MPA >65% (p=0.02) or PRU >235 (p=0.05) than non-carriers with HPR. Switching ACS patients during maintenance clopidogrel therapy to prasugrel with or without an LD is associated with a reduced HPR prevalence and may provide an alternative strategy to treat patients with HPR, independent of CYP2C19 genotype.
Trial registration:
ClinicalTrials.gov NCT00356135.
Publication types
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Clinical Trial, Phase II
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Multicenter Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Coronary Syndrome / blood
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Acute Coronary Syndrome / drug therapy*
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Aged
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Aryl Hydrocarbon Hydroxylases / genetics
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Aryl Hydrocarbon Hydroxylases / metabolism
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Blood Platelets / drug effects
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Blood Platelets / metabolism
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Cell Adhesion Molecules / blood
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Clopidogrel
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Cytochrome P-450 CYP2C19
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Double-Blind Method
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Drug Substitution*
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Female
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Genotype
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Humans
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Male
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Microfilament Proteins / blood
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Middle Aged
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Pharmacogenetics
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Phenotype
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Phosphoproteins / blood
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Piperazines / administration & dosage*
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Piperazines / adverse effects
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Piperazines / metabolism
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Platelet Aggregation / drug effects
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Platelet Aggregation Inhibitors / administration & dosage*
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Platelet Aggregation Inhibitors / adverse effects
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Platelet Aggregation Inhibitors / metabolism
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Platelet Function Tests
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Prasugrel Hydrochloride
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Prospective Studies
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Purinergic P2Y Receptor Antagonists / administration & dosage*
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Purinergic P2Y Receptor Antagonists / adverse effects
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Purinergic P2Y Receptor Antagonists / metabolism
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Receptors, Purinergic P2Y12 / blood
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Receptors, Purinergic P2Y12 / drug effects
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Thiophenes / administration & dosage*
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Thiophenes / adverse effects
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Thiophenes / metabolism
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Ticlopidine / administration & dosage
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Ticlopidine / adverse effects
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Ticlopidine / analogs & derivatives*
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Ticlopidine / metabolism
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Treatment Outcome
Substances
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Cell Adhesion Molecules
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Microfilament Proteins
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P2RY12 protein, human
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Phosphoproteins
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Piperazines
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Platelet Aggregation Inhibitors
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Purinergic P2Y Receptor Antagonists
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Receptors, Purinergic P2Y12
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Thiophenes
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vasodilator-stimulated phosphoprotein
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Clopidogrel
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Aryl Hydrocarbon Hydroxylases
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CYP2C19 protein, human
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Cytochrome P-450 CYP2C19
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Prasugrel Hydrochloride
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Ticlopidine
Associated data
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ClinicalTrials.gov/NCT00356135