Faculty Collaboration Database

Decrease in high on-treatment platelet reactivity (HPR) prevalence on switching from clopidogrel to prasugrel: insights from the switching anti-platelet (SWAP) study. Thromb Haemost 2013 Feb;109(2):347-55

Date

12/12/2012

Pubmed ID

23223867

DOI

10.1160/TH12-06-0378

Scopus ID

2-s2.0-84873284326 (requires institutional sign-in at Scopus site)   22 Citations

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.

Author List

Saucedo JF, Angiolillo DJ, DeRaad R, Frelinger AL 3rd, Gurbel PA, Costigan TM, Jakubowski JA, Ojeh CK, Duvvuru S, Effron MB, SWAP Investigators

Author

Jorge Saucedo MD Chief, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Coronary Syndrome
Aged
Aryl Hydrocarbon Hydroxylases
Blood Platelets
Cell Adhesion Molecules
Cytochrome P-450 CYP2C19
Double-Blind Method
Drug Substitution
Female
Genotype
Humans
Male
Microfilament Proteins
Middle Aged
Pharmacogenetics
Phenotype
Phosphoproteins
Piperazines
Platelet Aggregation
Platelet Aggregation Inhibitors
Platelet Function Tests
Prasugrel Hydrochloride
Prospective Studies
Purinergic P2Y Receptor Antagonists
Receptors, Purinergic P2Y12
Thiophenes
Ticlopidine
Treatment Outcome