Abstract 12703: Association of Serum Paraoxonase-1 With Platelet Responsiveness to Clopidogrel in Patients With Acute Coronary Syndromes
Introduction: Paraoxonase-1 (PON-1), a high density lipoprotein (HDL)-associated enzyme, is involved in the formation of clopidogrel's active thiol metabolite.
Hypothesis: PON-1 may significantly influence the antiplatelet efficacy of clopidogrel in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).
Methods: We studied 74 patients, aged 63.3±8.6 years, (52 men) with recent (<24 hours) ACS. Patients were loaded with 600 mg clopidogrel followed by 75 mg/day. PCI was performed within 4 days from clopidogrel loading. Serum HDL-cholesterol levels (HDL-C) and PON-1 activities towards paraoxon (paraoxonase activity) and phenylacetate (arylesterase activity) as well as platelet aggregation, P-selectin expression and platelet/leukocyte conjugates were determined before clopidogrel loading (baseline), and at 5-days and 30-days of follow-up. The clopidogrel response variability was evaluated by VASP analysis (PRI values).
Results: All baseline platelet activation parameters were progressively attenuated at 5-days and 30-days of follow-up, whereas baseline HDL-C levels (45.5±15.1 mg/dL), paraoxonase (81±38 U/L) and arylesterase (51±15 U/mL) activity were not altered during follow-up. HDL-C levels were inversely associated with all platelet activation parameters at baseline, 5-days and 30-days as well. At 5-days of follow-up, 17 patients were clopidogrel nonresponders (PRI: 64.2±11.1%), whereas at 30-days, these values were reduced to 41.2±16.1% (P<0.01). Only the paraoxonase activity of PON-1 was inversely associated with PRI values (r= -0.535, P<0.01 at 5-days and r= -0.608, P<0.005 at 30-days). In clopidogrel responders, PON-1 paraoxonase activity was inversely associated with all platelet activation parameters during follow-up whereas, in clopidogrel nonrespondrers a significant negative association between paraoxonase activity and all platelet activation parameters was observed only at 30-days of follow-up.
Conclusions: PON-1 influences clopidogrel antiplatelet efficacy in ACS patients, a phenomenon that is highly dependent on clopidogrel response variability and may be clinically important in clopidorel-treated patients, especially the first days after the episode.
- © 2011 by American Heart Association, Inc.