• Grant W Reed, Christopher P Cannon, Jill Waalen, Paul S Teirstein, Jean-Francois Tanguay, Peter B Berger, Dominick J Angiolillo, and Matthew J Price.
• Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
• Catheter Cardiovasc Interv. 2017 Feb 1; 89 (2): 190-198.

ObjectiveTo examine the influence of smoking on the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI).BackgroundCertain studies suggest smokers may have enhanced clopidogrel-induced platelet inhibition compared to non-smokers after PCI. Whether this is affected by clopidogrel dose is unknown.MethodsIn this study, we conducted an analysis of 5,429 patients in the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Platelet reactivity was assessed 12-24 hr after PCI (baseline). Patients with high on-treatment platelet reactivity (OTR) (P2Y12 reaction units [PRU] ≥ 230) were randomized to clopidogrel 75 mg or 150 mg daily. Reactivity was subsequently assessed at 30-days, and 6-months. Patients were stratified by smoking status.ResultsSmoking was independently associated with lower PRU (P = 0.001), and smokers were less likely to have high OTR (odds ratio 0.80, 95% confidence interval 0.68-0.94; P = 0.006) at baseline. Among patients assigned to clopidogrel 75 mg, smokers had lower PRU and were less likely to still have high OTR at 30-days (P < 0.001) and 6-months (P < 0.001). However, in patients assigned clopidogrel 150 mg, PRU and high OTR did not differ by smoking status at any time. Tests demonstrated an interaction between smoking and dose at 30 days (P = 0.007), and a trend at 6-months (P = 0.098).ConclusionsSmokers treated with clopidogrel exhibit reduced platelet reactivity and are less likely to have persistent high OTR than non-smokers. This difference is mitigated by clopidogrel 150 mg, indicating non-smokers may require double-dose therapy to achieve a similar antiplatelet effect after PCI. © 2016 Wiley Periodicals, Inc.© 2016 Wiley Periodicals, Inc.

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