Fatih AKSOY, Hasan Aydın BAŞ, Ali BAĞCI, Bayram Ali UYSAL, Seda AKSOY, Ercan VAROL, Ahmet ALTINBAŞ

ISPARTA VE ÇEVRESİNDE KLOPİDOGREL DİRENCİNİN ARAŞTIRILMASI

GirişAkut koroner sendrom (AKS) ile başvuran ve/veya stent uygulanan hastalarda klopidogrel tedavisi günümüzde önerilen tedavidir. Artan klopidogrel direnci (KD) ile kötü klinik sonlanımlar arasında ilişki mevcuttur. Bu nedenle, daha güçlü bir tedaviye geçmek veya hastaların yakından izlenmesi amacı ile KD’ne sahip hastaların tespit edilmesi klinik pratikte önemlidir. Antitrombositer ilaçların etkinliğini ölçmek için kullanılan trombosit fonksiyon testleri çoğu kez pahalı, zaman alıcı ve ulaşılması zor testlerdir. Klopidogrel direncini saptamak için pratik, kolay uygulanabilinir, ucuz ve güvenilir parametrelere ihtiyaç vardır.Gereç ve YöntemAkut Koroner Sendrom tanısı ile klopidogrel kullanan 531 hasta çalışmaya alındı. Alınan kan örneklerinde MEA (multiple electrod aggregometry) ile çalışıldı. Sonuçlar eğri altında kalan alan (AUC) cinsiden verildi. AUC > 470 olması klopidogrel direnci, (KD) olarak yorumlandı.BulgularToplamda 65 (%12,2) hastada klopidogrel direnci saptandı. Kadın hastalarda klopidogrel direnci anlamlı olarak fazlaydı (P=0,005). Risk faktörlerine bakıldığında ise hiperlipidemik ve diyabetik hastalarda klopidogrel direnci daha fazla görülürken, sigara içenlerde direnç daha az görülmekteydi (p=0,016, p< 0,001, p=0,046). Klopidogrel direnci olan hastalarda kalsiyum seviyesi, trombosit sayısı ve vücut kitle indeksi daha yüksek bulundu.SonuçBu çalışma, vücut kitle indeksi, diyabet, hiperlipidemi, kadın cinsiyet’in klopidogrel direnci açısından bir risk faktörü olabileceğini ortaya koymuştur.

INVESTIGATION OF CLOPIDOGREL RESISTANCE IN ISPARTA AREA

Objective Clopidogrel therapy is the standard of care in patients with acute coronary syndrome (ACS) and stent implantation. However, Clopidogrel resistance (CR) is arising increasingly and was associated with increased adverse outcomes. Therefore, detection of these subjects in daily practice is important in order to switch to more aggressive therapy and closer follow up. The platelet function tests for measurement aspirin and clopidogrel resistance are very expensive and time consuming. We need have practically, easily accessible, cheaper and reliable parameters for detecting CR. Material and Methods A total of 541 patients who had been on clopidogrel and aspirin therapy for the diagnosis of acute coronary syndrome were enrolled in this study. CR was analyzed by Multiplate MP-0120 device by using the method of whole blood aggregometry. The amount of ADP induced platelet aggregation was assessed as area under curve (AUC), and a cut off value of 470 for clopidogrel resistance above which the patient is considered as clopidogrel resistance, was used. Results Clopidogrel resistance was found in 65 patients, among the 541 patients analyzed. Among the 541 patients analyzed 65 were found to be CR (% 12.2). CR was more common in female sex, diabetes mellitus and hyperlipidemia history (p=0.005, p=0.016, p< 0.001). However, CR was reduced by smoking (p= 0.046). In patients with CR, calcium and platelet levels were higher than patients with normal clopidogrel response. Conclusion This study showed that hyperlipidemia, platelet count, body mass ındex and female gender are associated with CR

PDF

___

1. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). European heart journal. 2011;32(23):2999-3054.
2. Task Force on diabetes p-d, cardiovascular diseases of the European Society of C, developed in collaboration with the European Association for the Study of D. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD - Summary. Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease. 2014;11(3):133-73.
3. Task Force on the management of STseamiotESoC, Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European heart journal. 2012;33(20):2569-619.
4. Task Force M, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. European heart journal. 2013;34(38):2949-3003.
5. Herbert JM, Savi P. P2Y12, a new platelet ADP receptor, target of clopidogrel. Seminars in vascular medicine. 2003;3(2):113- 22.
6. Ben-Dor I, Kleiman NS, Lev E. Assessment, mechanisms, and clinical implication of variability in platelet response to aspirin and clopidogrel therapy. The American journal of cardiology. 2009;104(2):227-33.
7. Barsky AA, Arora RR. Clopidogrel resistance: myth or reality? Journal of cardiovascular pharmacology and therapeutics. 2006;11(1):47-53.
8. Notarangelo MF, Bontardelli F, Merlini PA. Genetic and nongenetic factors influencing the response to clopidogrel. Journal of cardiovascular medicine. 2013;14 Suppl 1:S1-7.
9. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. Journal of the American College of Cardiology. 2007;49(14):1505-16.
10. Cohen MV, Downey JM. Combined Cardioprotectant and Antithrombotic Actions of Platelet P2Y12 Receptor Antagonists in Acute Coronary Syndrome: Just What the Doctor Ordered. Journal of cardiovascular pharmacology and therapeutics. 2014;19(2):179-90.
11. Sibbing D, Schulz S, Braun S, Morath T, Stegherr J, Mehilli J, et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. Journal of thrombosis and haemostasis : JTH. 2010;8(2):250-6.
12. Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schomig A, et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. Journal of the American College of Cardiology. 2009;53(10):849-56.
13. Snoep JD, Hovens MM, Eikenboom JC, van der Bom JG, Jukema JW, Huisman MV. Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. American heart journal. 2007;154(2):221-31.
14. Chen WH, Lee PY, Ng W, Tse HF, Lau CP. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. Journal of the American College of Cardiology. 2004;43(6):1122-6.
15. Antithrombotic Trialists C, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849-60.
16. Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. Journal of the American College of Cardiology. 2005;45(8):1157-64.
17. Sharma RK, Erickson SW, Sharma R, Voelker DJ, Reddy HK, Dod H, et al. Platelet function testing to predict hyporesponsiveness to clopidogrel in patients with chest pain seen in the emergency department. Vascular health and risk management. 2013;9:187-93.
18. Bozbeyoglu E, Satilmis S, Aksu H, Yildirimturk O, Nurkalem Z. Impact of clopidogrel resistance on ST-segment resolution and no-reflow in acute myocardial infarction with ST-elevation patients treated with a primary percutaneous coronary intervention. Coronary artery disease. 2012;23(8):523-7.
19. Angiolillo DJ, Bernardo E, Zanoni M, Vivas D, Capranzano P, Malerba G, et al. Impact of insulin receptor substrate-1 genotypes on platelet reactivity and cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. Journal of the American College of Cardiology. 2011;58(1):30- 9.
20. Grove EL, Hvas AM, Kristensen SD. Immature platelets in patients with acute coronary syndromes. Thrombosis and haemostasis. 2009;101(1):151-6.
21. Ferreiro JL, Gomez-Hospital JA, Angiolillo DJ. Platelet abnormalities in diabetes mellitus. Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease. 2010;7(4):251-9.
22. Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis RJ, et al. Body-mass index and mortality among 1.46 million white adults. The New England journal of medicine. 2010;363(23):2211-9.
23. Sibbing D, von Beckerath O, Schomig A, Kastrati A, von Beckerath N. Impact of body mass index on platelet aggregation after administration of a high loading dose of 600 mg of clopidogrel before percutaneous coronary intervention. The American journal of cardiology. 2007;100(2):203-5.
24. Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood. 2013;122(20):3415-22.
25. Darvall KA, Sam RC, Silverman SH, Bradbury AW, Adam DJ. Obesity and thrombosis. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. 2007;33(2):223-33.
26. Desai NR, Mega JL, Jiang S, Cannon CP, Sabatine MS. Interaction between cigarette smoking and clinical benefit of clopidogrel. Journal of the American College of Cardiology. 2009;53(15):1273-8.
27. Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, et al. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010;376(9748):1233-43.
28. Gurbel PA, Nolin TD, Tantry US. Clopidogrel efficacy and cigarette smoking status. JAMA : the journal of the American Medical Association. 2012;307(23):2495-6.
29. Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW. Smoking promotes clopidogrel-mediated platelet inhibition in patients receiving dual antiplatelet therapy. Thrombosis research. 2009;124(5):588-91.
30. Matetzky S, Shenkman B, Guetta V. Clopidogel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. 2004; 109(25): . Circulation. 2004;109(25): :3171-5
31. Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation. 2003;107(1):32-7.
32. Saw J, Brennan DM, Steinhubl SR, Bhatt DL, Mak KH, Fox K, et al. Lack of evidence of a clopidogrel-statin interaction in the CHARISMA trial. Journal of the American College of Cardiology. 2007;50(4):291-5.
33. Li L, Han JL, Li HY, Qiao R, Yu HY, Zhang J, et al. [Clopidogrel resistance of patients with coronary artery disease and its correlation with platelet count and mean platelet volume]. Zhonghua yi xue za zhi. 2013;93(12):916-20.
34. Takahashi S, Ushida M, Komine R, Shimizu A, Uchida T, Ishihara H, et al. Increased basal platelet activity, plasma adiponectin levels, and diabetes mellitus are associated with poor platelet responsiveness to in vitro effect of aspirin. Thrombosis research. 2007;119(4):517-24.