Grant W Reed1, Christopher P Cannon2, Jill Waalen3, Paul S Teirstein, Jean-Francois Tanguay4, Peter B Berger5, Dominick J Angiolillo6, Matthew J Price3. 1. Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio. 2. Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. 3. Department of Cardiology, Scripps Translational Science Institute, Scripps Clinic, La Jolla, California. 4. Department of Medicine, Institut De Cardiologie De Montreal, Montreal, Quebec, Canada. 5. Department of Cardiology, Geisinger Clinic, Danville, Pennsylvania. 6. Division of Cardiology, University of Florida College of Medicine, Jacksonville, Florida.
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.
RCT Entities:
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.
Authors: Shadi Yaghi; Pooja Khatri; Adam de Havenon; Sharon Yeatts; Andrew D Chang; Shawna Cutting; Brian Mac Grory; Tina Burton; Mahesh V Jayaraman; Ryan A McTaggart; David Fiorella; Colin Derdeyn; Osama O Zaidat; Seena Dehkharghani; Sepideh Amin-Hanjani; Karen Furie; Shyam Prahbakaran; David Liebeskind Journal: J Neurointerv Surg Date: 2019-09-04 Impact factor: 5.836
Authors: Krzysztof Kukula; Mariusz Klopotowski; Joanna Was; Aleksandra Wrobel; Jacek Jamiolkowski; Artur Debski; Pawel Bekta; Zbigniew Chmielak; Adam Witkowski Journal: Postepy Kardiol Interwencyjnej Date: 2017-09-25 Impact factor: 1.426