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  • Title: Influence of smoking on the antiplatelet effect of clopidogrel differs according to clopidogrel dose: Insights from the GRAVITAS trial.
    Author: Reed GW, Cannon CP, Waalen J, Teirstein PS, Tanguay JF, Berger PB, Angiolillo DJ, Price MJ.
    Journal: Catheter Cardiovasc Interv; 2017 Feb 01; 89(2):190-198. PubMed ID: 26909669.
    Abstract:
    OBJECTIVE: To examine the influence of smoking on the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI). BACKGROUND: Certain 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. METHODS: In 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. RESULTS: Smoking 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). CONCLUSIONS: Smokers 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.
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