Influence of smoking on the antiplatelet effect of clopidogrel differs according to clopidogrel dose: Insights from the GRAVITAS trial

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