Effect of Smoking on Antiplatelet Action of  Clopidogrel in Patients with Ischemic Heart Disease

Usman  Nawaz; Mudassar Noor; Waqar Aslam  Khan; Salman  Bakhtiyar; Amina  Nawaz

doi:10.51253/pafmj.v74i6.10305

Authors

Usman Nawaz Department of Pharmacology, Combined Military Hospital Kharian /National University of Medical Sciences (NUMS) Pakistan
Mudassar Noor Department of Pharmacology, Army Medical College Rawalpindi/National University of Medical Sciences (NUMS) Pakistan
Waqar Aslam Khan Department of Pharmacology, Combined Military Hospital Kharian /National University of Medical Sciences (NUMS) Pakistan
Salman Bakhtiyar Department of Pharmacology, Sharif Medical and Dental College Lahore Pakistan
Amina Nawaz Department of Infectious Diseases, Shifa International Hospitals, Islamabad Pakistan

DOI:

https://doi.org/10.51253/pafmj.v74i6.10305

Keywords:

Clopidogrel, Platelet Aggregation, Smoking

Abstract

Objective: To explore relationship between smoking and antiplatelet action of Clopidogrel in patients with ischemic heart disease (IHD).

Study Design: Quasi-experimental study

Place and Duration of Study: Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan from Aug 2015 to Dec 2019.

Methodology: The quasi experimental study was carried out on 390 patients with IHD recruited through convenience sampling. Patients were placed in two groups. Group-1 included smokers while group-2 patients were nonsmokers. Blood samples of smokers (n=151) and nonsmokers (n=239) IHD patients were taken. Platelet function testing of all the samples was done through light transmission aggregometer (LTA) using adenosine diphosphate (ADP) as an agonist.

Results: Among patients of IHD 82.12% of the smokers on Clopidogrel therapy were Clopidogrel responders and 17.88% were Clopidogrel resistant, while in nonsmoker group 70.71% patients were Clopidogrel responders and 29.29% were Clopidogrel resistant. There was a significant difference in Clopidogrel response status between smokers and nonsmokers, p=0.011. Furthermore, mean platelet aggregation of smokers was significantly lower than that of nonsmokers, p=0.004.

Conclusion: Smoking can enhance antiplatelet effect of Clopidogrel in IHD patients with greater platelet inhibition and lesser chances of Clopidogrel resistance.

Downloads

Download data is not yet available.

References

Yuan X wen, Yuan S yun, Wu G xin, Wu Z xin, Guan Z yun. Genetic polymorphism of Clopidogrel metabolism related gene CYP2C19 gene in Chinese from Foshan area of Guangdong Province. Hematology 2022; 27(1): 1056–1061.

https://doi.org/10.1080/16078454.2022.2121899

Tariq M, Akhtar FN, Babar MAK. Trends in prescribing antiplatelet drugs for secondary prevention of non-cardioembolic ischemic stroke. Pak Armed Forces Med J 2018; 68(6): 1744–1748.

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; 120(03): 449–456.

https://doi.org/10.1055/s-0039-3402758

Ferreiro JL, Bhatt DL, Ueno M, Bauer D, Angiolillo DJ. Impact of smoking on long-term outcomes in patients with atherosclerotic vascular disease treated with aspirin or Clopidogrel: insights from the CAPRIE trial (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events). J Am Coll Cardiol 2014; 63(8): 769–777. https://doi.org/10.1016/j.jacc.2013.10.043

Jeong YH, Cho JH, Kang MK, Koh JS, Kim IS, Park Y, et al. Smoking at least 10 cigarettes per day increases platelet inhibition by Clopidogrel in patients with ST-segment-elevation myocardial infarction. Thromb Res 2010; 126(4): e334–338.

https://doi.org/10.1016/j.thromres.2010.03.020

Bliden KP, DiChiara J, Lawal L, Singla A, Antonino MJ, Baker BA, et al. The association of cigarette smoking with enhanced platelet inhibition by Clopidogrel. J Am Coll Cardiol 2008; 52(7): 531–533.

https://doi.org/10.1016/j.jacc.2008.04.045

Hidayat R, Nabilah RA, Rasyid A, Harris S, Harahap AR, Louisa M, et al. Clopidogrel Resistance Among Ischemic Stroke Patients and Its Risk Factors in Indonesia. Acta Med Acad 2022; 51(1). https://doi.org/10.5644/ama2006-124.367

Cai Y, Xu W, Liu H, Wang F, Duan L, Li H, et al. Effects of cigarette smoking on older Chinese men treated with Clopidogrel monotherapy or aspirin monotherapy: a prospective study. Platelets 2020; 31(5): 667–673. https://doi.org/10.1080/09537104.2019.1667494

Wiśniewski A, Filipska K. The phenomenon of Clopidogrel high on-treatment platelet reactivity in ischemic stroke subjects: a comprehensive review. Int J Mol Sci 2020; 21(17): 6408. https://doi.org/10.3390/ijms21176408

Mohydin BS, Bashir F, Ahmad S, Hameedc A, Azim S, Khan BZ. Coronary intervention and Clopidogrel resistance-a local experience. J Cardiovacular Dis 2013; 11(1): 14.

Shalia KK, Shah VK, Pawar P, Divekar SS, Payannavar S. Polymorphisms of MDR1, CYP2C19 and P2Y12 genes in Indian population: Effects on Clopidogrel response. Indian Heart J 2013; 65(2): 158–167.

https://doi.org/10.1016/j.ihj.2013.02.012

Park KW, Park JJ, Jeon KH, Kang SH, Oh IY, Yang HM, et al. Enhanced Clopidogrel responsiveness in smokers: smokers’ paradox is dependent on cytochrome P450 CYP1A2 status. Arterioscler Thromb Vasc Biol 2011; 31(3): 665–671. https://doi.org/10.1161/atvbaha.110.217182

Kang HG, Lee SJ, Heo SH, Chang D il, Kim BJ. Clopidogrel Resistance in Patients With Stroke Recurrence Under Single or Dual Antiplatelet Treatment. Front Neurol 2021 10; 12: 652416. https://doi.org/10.3389/fneur.2021.652416

Berger JS, Bhatt DL, Steinhubl SR, Shao M, Steg PG, Montalescot G, et al. Smoking, Clopidogrel, and mortality in patients with established cardiovascular disease. Circulation 2009; 120(23): 2337–2344. https://doi.org/10.1161/CIRCULATIONAHA.109.866533

Dobrinas M, Cornuz J, Oneda B, Kohler Serra M, Puhl M, Eap CB. Impact of smoking, smoking cessation, and genetic polymorphisms on CYP1A2 activity and inducibility. Clin Pharmacol Ther 2011; 90(1): 117–125.

https://doi.org/10.1038/clpt.2011.70

Chetty M, Ravenstijn P, Manchandani P. Clopidogrel Dosing: Current Successes and Emerging Factors for Further Consideration. Clin Pharmacol Ther 2021; 109(5): 1203–1211.

https://doi.org/10.1002/cpt.2055

Ramotowski B, Gurbel PA, Tantry U, Budaj A. Smoking and cardiovascular diseases: paradox greater than expected? Polish Arch Intern Med 2019; 129(10): 700–706.

https://dx.doi.org/10.20452/pamw.14931

Gagne JJ, Bykov K, Choudhry NK, Toomey TJ, Connolly JG, Avorn J. Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison. BMJ 2013 17; 347: f5307.

https://doi.org/10.1136/bmj.f5307