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

Publication ,  Journal Article
Ramotowski, B; Gurbel, PA; Tantry, U; Bracha, JS; Karaźniewicz-Łada, M; Lewandowski, Z; Budaj, A
Published in: Thromb Haemost
March 2020

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.

Duke Scholars

Published In

Thromb Haemost

DOI

EISSN

2567-689X

Publication Date

March 2020

Volume

120

Issue

3

Start / End Page

449 / 456

Location

Germany

Related Subject Headings

  • Stents
  • Smoking Cessation
  • Sample Size
  • Risk
  • Platelet Aggregation Inhibitors
  • Platelet Aggregation
  • Percutaneous Coronary Intervention
  • Middle Aged
  • Male
  • Humans
 

Citation

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Ramotowski, B., Gurbel, P. A., Tantry, U., Bracha, J. S., Karaźniewicz-Łada, M., Lewandowski, Z., & Budaj, A. (2020). Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study. Thromb Haemost, 120(3), 449–456. https://doi.org/10.1055/s-0039-3402758
Ramotowski, Bogumił, Paul A. Gurbel, Udaya Tantry, Jan S. Bracha, Marta Karaźniewicz-Łada, Zbigniew Lewandowski, and Andrzej Budaj. “Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study.Thromb Haemost 120, no. 3 (March 2020): 449–56. https://doi.org/10.1055/s-0039-3402758.
Ramotowski B, Gurbel PA, Tantry U, Bracha JS, Karaźniewicz-Łada M, Lewandowski Z, et al. Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study. Thromb Haemost. 2020 Mar;120(3):449–56.
Ramotowski, Bogumił, et al. “Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study.Thromb Haemost, vol. 120, no. 3, Mar. 2020, pp. 449–56. Pubmed, doi:10.1055/s-0039-3402758.
Ramotowski B, Gurbel PA, Tantry U, Bracha JS, Karaźniewicz-Łada M, Lewandowski Z, Budaj A. Effect of Smoking Cessation on the Pharmacokinetics and Pharmacodynamics of Clopidogrel after PCI: The Smoking Cessation Paradox Study. Thromb Haemost. 2020 Mar;120(3):449–456.
Journal cover image

Published In

Thromb Haemost

DOI

EISSN

2567-689X

Publication Date

March 2020

Volume

120

Issue

3

Start / End Page

449 / 456

Location

Germany

Related Subject Headings

  • Stents
  • Smoking Cessation
  • Sample Size
  • Risk
  • Platelet Aggregation Inhibitors
  • Platelet Aggregation
  • Percutaneous Coronary Intervention
  • Middle Aged
  • Male
  • Humans