Sigara kulanımının klopidogrel tedavisi alan hastalarda P2Y12 trombosit fonksiyon testi ile değerlendirilen trombosit reaktivitesi üzerine etkisi

Yıl 2020, Cilt: 3 Sayı: 1, 42 - 46, 15.01.2020

Taner Sarak , Ersin Saricam , Abbas Taner

https://doi.org/10.32322/jhsm.654901

Öz

Amaç: Sigara içimi ve trombosit fonksiyon testinin etkinliği arasındaki etkileşim kesin olarak gösterilmemiştir. Bu çalışmada klopidogrel ile tedavi edilen hastalarda sigara içiminin P2Y12 trombosit fonksiyon testi ile belirlenen trombosit reaktivitesi üzerine etkilerini araştırmayı amaçladık.
Gereç ve Yöntemler: Bu prospektif çalışmaya daha önce stent implantasyonu yapılan ve klopidogrel kullanan 200 hasta dahil edildi. Bu hastalara göğüs ağrısı nedeniyle tanısal koroner anjiyografi yapıldı ve klopidogrel rezistans testi uygulandı. Ayrıca, trombosit reaktivitesi üzerindeki sigara etkisi araştırıldı.
Bulgular: P2Y12 trombosit fonksiyon testi ile hastaların% 17'sinin (34/200) klopidogrel dirençli olduğunu bulduk. Anjiyografik stent restenoz ile klopidogrel direnci arasında ilişki tespit etmedik (p > 0.05). Ancak sigara içme ve klopidogrel direnci arasında istatistiksel olarak anlamlı ilişki vardı. Yine sigara içenlerde VerifyNow P2Y12 testiyle tespit edilen trombosit reaktivite seviyeleri de yüksekti (> 208 PRU).
Sonuç: Sigara içenlerde P2Y12 trombosit fonksiyon testi ile tespit ettiğimiz klopidogrel direnci beklendiği gibi stent restenoz oranlarında yükseklik ile paralellik göstermedi. Bu yüzden sigara içenlerde P2Y12 trombosit fonksiyon testi klinik bulgularla uyumlu olan net sonuçlar vermeyebilir.

Anahtar Kelimeler

Klopidogrel direnci, koroner arter hastalığı, sigara kullanımı

Destekleyen Kurum

Yok

Proje Numarası

yok

The Effect Of Smoking On Platelet Reactivity Assessed By P2Y12 Platelet Function Testing In Patient With Clopidogrel Therapy

Öz

Aim: The interaction between cigarette smoking and efficacy of platelet function testing is not definitely shown. We aimed to conduct the effects of smoking on platelet reactivity by P2Y12 platelet function testing on the patients treated with clopidogrel.
Materials and Methods: This prospective study contained 200 patients who underwent a previous stent implantation. Diagnostic coronary angiography was performed those patients due to chest pain. The clopidogrel resistance test was applied. Furthermore, the smoking effect on platelet reactivity was investigated.
Results: We found that 17% of the patients (34/200) clopidogrel-resistant by P2Y12 platelet function test. We didn’t find any relationship between angiographic stent restenosis and clopidogrel resistance (p>0.05). There was statistically significant relationship between smoking and clopidogrel resistance. The smokers had also higher platelet reactivity level (>208 PRUs) as revealed by VerifyNow P2Y12 assay.
Conclusion: The test results achieved through the clopidogrel resistance by P2Y12 platelet function testing did not meet expectation with the angiographically observations. Therefore, P2Y12 platelet function testing can be unclear in smoker patients.

Anahtar Kelimeler

Clopidogrel resistance, coronary artery disease, smoking

Proje Numarası

yok

Kaynakça

• 1-Byrne RA, Joner M, Kastrati A. Stent thrombosis and restenosis: what have we learned and where are we going? The Andreas Grüntzig Lecture ESC 2014 Eur Heart J. 2015 14; 36(47):3320-31.
• 2-Herbert JM, Savi P. P2Y12, a new paltelet ADP receptor, target of clopidogrel. Semin Vasc Med 2003;3:113-22
• 3-Matetzky S, Shenkman B, Guetta V, Shechter M, Beinart R, Goldenberg I, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004;109:3171-5
• 4-Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction.J Am Coll Cardiol. 2016 Mar 15; 67(10):1235-50.
• 5-Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, at al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology. Eur Heart J. 2016 Jan 14; 37(3):267-315.
• 6-Sibbing D, Gross L. Smoking and Clopidogrel Response Revisited: Hemoglobin Levels Explaining the Smoker's Paradox. JACC Cardiovasc Interv. 2016 ;9(16):1691- 3.
• 7-Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2014 Nov 4;64(18):1929-49.
• 8-van Werkum JW, van der Stelt CA, Seesing TH, Hackeng CM, ten Berg JM. A head- to-head comparison between the VerifyNow P2Y12 assay and light transmittance aggregometry for monitoring the individual platelet response to clopidogrel in patients undergoing elective percutaneous coronary intervention. J Thromb Haemost 2006; 4:2516–8.
• 9-Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 2010;304:1821–1830.
• 10-Attizzani GF, Capodanno D, Ohno Y, Tamburino C. Mechanisms, pathophysiology, and clinical aspects of incomplete stent apposition. J Am Coll Cardiol 2014; 63:1355– 1367.
• 11-Lüscher TF, Steffel J, Eberli FR et al. Drug-eluting stent and coronary thrombosis: Biological mechanisms and clinical implications. Circulation, 2007; 115: 1051–1058.
• 12-Finn AV, Joner M, Nakazawa G et al. Pathological correlates of late drug-eluting stent thrombosis: Strut coverage as a marker of endothelialization. Circulation, 2007; 115: 2435–24.
• 13-Joner M, Finn AV, Farb A. et al. Pathology of drug-eluting stents in humans: Delayed healing and late thrombotic risk. J Am Coll Cardiol, 2006; 48: 193–202.
• 14-Ray S. Clopidogrel resistance: the way forward. Indian Heart J. 2014 ; 66(5):530-4.
• 15-Dibra A, Mehilli J, Braun S, Hadamitzky M, Baum H, Dirschinger J, Schuhlen H, Schomig A, Kastrati A. Inflammatory response after intervention assessed by serial C- reactive protein measurements correlates with restenosis in patients treated with coronary stenting. Am Heart J 2005; 150:344–350.
• 16-Ueno M, Ferreiro JL, Desai B, Tomasello SD, Tello-Montoliu A, Capodanno D, Capranzano P, Kodali M, Dharmashankar K, Charlton RK, Bass TA, Angiolillo DJ. Cigarette smoking is associated with a dose-response effect in clopidogrel-treated patients with diabetes mellitus and coronary artery disease: results of a pharmacodynamic study. JACC Cardiovasc Interv. 2012 Mar; 5(3):293-300.
• 17-Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW. Smoking promotes clopidogrel-mediated platelet inhibition in patients receiving dual antiplatelet therapy. Thromb Res. 2009 Nov; 124(5):588-91.
• 18-Kim YG, Suh J-W, Kang S-H, et al. Cigarette smoking does not enhance clopidogrel responsiveness after adjusting VerifyNow P2Y12 reaction unit for the influence of hemoglobin level. J Am Coll Cardiol Intv 2016; 9:1680–90.
• 19-Patti G, Polacco M, Taurino E, Gaudio C, Greco C. Effects of cigarette smoking on platelet reactivity during P2Y12 inhibition in patients with myocardial infarction undergoing drug-eluting stent implantation: results from the prospective cigarette smoking on platelet reactivity (COPTER) study. J Thromb Thrombolysis 2016; 41:648–53.
• 20-J.S. Jang, K.I. Cho, H.Y. Jin, et al., Meta-analysis of cytochrome P450 2C19 polymorphism and risk of adverse clinical outcomes among coronary artery disease patients of different ethnic groups treated with clopidogrel. Am J Cardiol 2012; 110: 502–508.