Abstract 18950: Clopidogrel Loading Dose Adjustment According to Platelet Reactivity Monitoring in Patients Carrying the 2c19 2* Loss of Function Polymorphism.
Objectives: We aimed to investigate the biological impact of tailored clopidogrel loading dose(LD) according to platelet reactivity(PR) monitoring in carriers of the cytochromes(CYP) 2C19 2* loss-of function polymorphism undergoing percutaneous coronary intervention(PCI) for an acute coronary syndromes(ACS).
Background: CYP 2C19 2* polymorphism is associated with reduced clopidogrel metabolism and a worse prognosis after PCI.
Method: A prospective multicenter study enrolling 411 non-ST elevation ACS patients undergoing PCI was performed. PR was measured using the Vasodilator-Stimulated Phosphoprotein(VASP) index and a cut-off value of ≥50% was used to define high on-treatment platelet reactivity(HTPR). Genetic polymorphism of CYP 2C19 was determined by allele specific PCR. In patients carrying CYP 2C19 2* and exhibiting HTPR following a first 600mg LD of clopidogrel, dose adjustment was performed by using up-to three additional 600mg LD in order to obtain a VASP<50%.
Results: One hundred and thirty four patients(35.3%) carried at least one 2C19 2* alleles (11 homozygotes(2.7%) and 123 heterozygotes(32.6%)). The mean VASP index in these patients was significantly higher than patients homozygotes for the wild-type alleles (61.7±18.4 vs 49.2±24.2% p<0.001). Among the 134 carriers of the loss-of function polymorphism, 103 were considered to have HTPR. After a second clopidogrel LD, the mean VASP was significantly decreased in these patients (69.7±10.1 vs 50.6±17.6% p<0.0001). Finally, dose-adjustment according to PR monitoring, enabled 88% of 2C19 2* carriers exhibiting HTPR to reach a VASP index<50%.
Conclusions: Increased and tailored clopidogrel loading dose according to platelet reactivity monitoring overcome HTPR in carriers of the loss-of function 2C19 2* polymorphism.
- Acute coronary syndromes
- Antiplatelet drugs
- Percutaneous coronary intervention
- © 2010 by American Heart Association, Inc.