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

Reed, Grant W.; Cannon, Christopher P.; Waalen, Jill; Teirstein, Paul S.; Tanguay, Jean‐François; Berger, Peter B.; Angiolillo, Dominick J.; Price, Matthew J.

doi:10.1002/ccd.26428

Cited by 20 publications

(14 citation statements)

References 43 publications

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“…11 In the platelet substudy of the GRAVITAS trial, the difference in platelet aggregation between smokers and nonsmokers treated with clopidogrel was observed only in patients treated with the standard dose of clopidogrel, not in those treated with the double dose. 27 This finding supports the potential use of the double dose of clopidogrel following smoking cessation. Another option would be treatment with prasugrel, which is a thienopyridine that does not share the same metabolic pathway as clopidogrel or ticagrelor, a direct-acting P2Y 12 inhibitor.…”

Section: Discussionsupporting

confidence: 61%

Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study

et al. 2020

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Background Cigarette smoking is associated with enhanced clopidogrel effect and platelet inhibition. However, the effect of smoking cessation on clopidogrel pharmacokinetics (PK) and pharmacodynamics (PD) is unknown. We aimed to determine the effect of smoking cessation, confirmed by cotinine measurement, on clopidogrel PK and PD after percutaneous coronary intervention (PCI). Methods and Results Following successful PCI, patients treated with 75 mg/day clopidogrel who reported smoking ≥10 cigarettes/day with NicAlert urine cotinine level 6 were enrolled. Clopidogrel and its metabolite concentrations, VerifyNow P2Y12 reaction units (PRUs), and NicAlert levels were measured in the study group before and at 30 days after smoking cessation and in a control group. CYP1A2 and CYP2C19 genotypes were determined. At 30-day visit (n = 87), 45 patients continued smoking, whereas 42 patients stopped smoking. Baseline PRUs were similar between groups. At 30 days, the smoking cessation group had higher PRUs (150.5 ± 68.6 vs. 118.4 ± 65.9, p = 0.03), greater absolute PRU change (27.7 ± 39.8 vs. −12.9 ± 55.4, p = 0.0002), greater change of PRUs adjusted for baseline platelet reactivity (38.6 ± 10.0, p < 0.01), greater risk of high platelet reactivity (HPR) (odds ratio: 10.14 [1.52–67.5], p = 0.017), and a trend towards decreased H3 clopidogrel metabolite levels (−3.41 ng/mL [−11.00 to 0.54 ng/mL], p = 0.072). CYP2C19 LoF carriers who stopped smoking had the highest PRUs, whereas those with the wild type who continued smoking had the lowest PRUs (p < 0.008). Conclusion Smoking cessation in clopidogrel-treated patients after PCI is associated with increased platelet reactivity and greater risk of HPR. Alternative P2Y12 inhibitors may be considered in selected patients who stop smoking after PCI.

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Section: Discussionsupporting

confidence: 61%

Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study

et al. 2020

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“…In contrast, double-dose clopidogrel eliminated the difference due to smoking status, resulting in similar levels of platelet activity between smokers and non-smokers. 35 We do not encourage cigarette smoking based on the present study results. Smoking induces hypercoagulability and results in early MI, as shown in the present study.…”

Section: In-hospital Adjusted Outcomescontrasting

confidence: 53%

Effect of Smoking Status on Clinical Outcome and Efficacy of Clopidogrel in Acute Coronary Syndrome

Kodaira

Matsubara

Numasawa

et al. 2016

Circ J

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“…The ‘smoking paradox’ has been demonstrated in patients undergoing cardiac stents, who had lower early mortality 11. In addition, another study showed that smokers tend to have more platelet inhibition in response to clopidogrel than non-smokers 12. A meta-analysis, however, showed no effect of smoking on major cardiovascular events but an increased risk of major cardiovascular and cerebrovascular events in smokers (vs non-smokers) undergoing coronary stenting (OR 2.09, 95% CI 1.43 to 3.06) 13.…”

Section: Discussionmentioning

confidence: 99%

Peri-procedural stroke or death in stenting of symptomatic severe intracranial stenosis

Yaghi

Khatri

Havenon

et al. 2019

J NeuroIntervent Surg

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Background and purposeThere are limited data on predictors of 30-day stroke or death in patients with symptomatic intracranial atherosclerosis (sICAS) undergoing stenting. We aim to determine the factors associated with stroke or death at 30 days in the stenting arm of the SAMMPRIS trial.MethodsThis is a post-hoc analysis of the SAMMPRIS trial including patients who underwent angioplasty/stenting. We compared patient-specific variables, lesion-specific variables, procedure-specific variables, and FDA-approved indications between patients with and without the primary outcome (stroke or death at 30 days). Logistic regression analyses were performed to evaluate associations with the primary outcome.ResultsWe identified 213 patients, 30 of whom (14.1%) met the primary outcome. Smoking status and lesion length were associated with the primary outcome: the odds of stroke or death for non-smokers versus smokers (adjusted OR 4.46, 95% CI 1.79 to 11.1, p=0.001) and for increasing lesion length in millimeters (adjusted OR 1.20, 95% CI 1.02 to 1.39, p=0.029). These had a modest predictive value: absence of smoking history (sensitivity 66.7%, specificity 65.4%) and lesion length (area under curve 0.606). Furthermore, event rates were not significantly different between patients with and without the FDA-approved indication for stenting (15.9% vs 12%, p=0.437).ConclusionIn SAMMPRIS patients who underwent angioplasty/stenting, neither clinical and neuroimaging variables nor the FDA indication for stenting reliably predicted the primary outcome. Further work in identifying reliable biomarkers of stroke/death in patients with sICAS is needed before considering new clinical trials of stenting.Trial registration numberSAMMPRIS NCT00576693; Results.

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

Cited by 20 publications

References 43 publications

Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study

Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study

Effect of Smoking Status on Clinical Outcome and Efficacy of Clopidogrel in Acute Coronary Syndrome

Peri-procedural stroke or death in stenting of symptomatic severe intracranial stenosis

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