Enhanced Clopidogrel Response in Smokers is Reversed After Discontinuation as Assessed by VerifyNow Assay

Abstract

Introduction: Previous reports on smokers paradox to clopidogrel have only been able to show an association between cigarette smoking and enhanced response to clopidogrel therapy. No study has shown reversal of enhanced clopidogrel response after smoking cessation. We conducted a prospective observational longitudinal study to measure the impact of cigarette smoking on on-clopidogrel platelet reactivity (OPR). Methods: From the prospective CROSS-VERIFY cohort, 810 subjects with repeated measurement of OPR at least 1 month apart were analyzed. With smoking status ascertained at 2 time points, baseline and follow-up, study subjects were categorized into never smokers (n=628), smoking quitters (n=77), and persistent smokers (n=105). Dependent variables included OPR measured by the VerifyNowTM assay and the percentage of subjects with high OPR (HOPR). Results: At baseline, current smokers showed significantly lower OPR compared with never smokers, with no significant differences in OPR between future quitters and future persistent smokers within current smokers. While the OPR of never smokers and persistent smokers did not change significantly during the follow-up, the mean OPR of quitters increased significantly by 19 P2Y12 reaction units (p=0.013). The frequency of HOPR showed similar results with an 8-10% increase in smoking quitters in contrast to no significant changes in never and persistent smokers. Both mean OPR and the frequency of HOPR showed a linear inverse relationship with the amount of smoking. Conclusions: Enhanced clopidogrel response in smokers is reversed after smoking discontinuation, suggesting causal relationship in addition to previously reported association between smoking and enhanced clopidogrel response.