Investigation of acetylsalicylic acid resistance in patients with acute coronary syndrome

Yıl 2019, Cilt: 10 Sayı: 2, 167 - 171, 16.06.2019

Fatih Aksoy Hasan Aydın Baş Ali Bağcı Ercan Varol Ahmet Altınbaş

https://doi.org/10.22312/sdusbed.539426

Öz

Background: Aspirin and clopidogrel therapy is the standard
of care in patients with acute coronary syndrome (ACS) and stent implantation.
However, Clopidogrel and aspirin resistance are arising increasingly. As this
nonresponsiveness is associated with increased adverse outcome, detection of
these subjects in daily practice is important in order to withhold a 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 aspirin and clopidogrel resistance

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. Aspirin resistance 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 500 for aspirin resistance, above which the patient is
considered as aspirin resistant, was used.

Results:  Among
the 541 patients analyzed, 45 were found aspirin nonresponder (8.5%). Diabetes
Mellitus, Hyperlipidemia, calcium levels, platelet levels, were predictory
factor for aspirin resistance.

Conclusion: This study showed that diabetes mellitus,
hyperlipidemia, calcium levels, platelet levels are associated with aspirin resistance
especially in patients with ACS.

Anahtar Kelimeler

aspirin resistance, acute coronary syndrome, risk factors

Akut Koroner Sendrom ile Başvuran Hastalarda Asetil Salisilik Asit Direncinin Araştırılması

Öz

Giriş ve amaç:
Akut koroner sendrom (AKS) ile başvuran ve/veya stent uygulanan hastalarda
klopidogrel ve aspirin tedavisi günümüzde standart tedavidir. Bununla beraber
klopidogrel tedavisine yanıtsızlık olumsuz sonuçlarla ilişkili olması nedeni
ile günümüzde önemli bir sorundur. Antitrombositer ilaçların etkinliğini ölçmek
için kullanılan trombosit fonksiyon testleri çoğu kez pahalı, zaman alıcı ve
ulaşılması zor testlerdir. Aspirin ve klopidogrel direncini saptamak için
pratik, kolay uygulanabilinir, ucuz ve güvenilir parametrelere ihtiyaç vardır.

Metot: Akut
Koroner Sendrom tanısı ile klopidogrel ve aspirin kullanan 531 hasta çalışmaya
alındı. Alınan kan örneklerinde MEA (multiple electrod aggregometry) ile
çalışıldı. Sonuçlar eğri altında kalan alan (AUC) cinsiden verildi. AUC>500
olması aspirin direnci olarak yorumlandı.

Bulgular:       Toplamda 45  (%8,5) hastada ise aspirin direnci
saptandı.  Aspirin direnci için ise
diyabet, hiperlipidemi, ürik asit düzeyi, LDL kolesterol düzeyi, non-HDL
kolesterol düzeyi, kalsiyum düzeyi, trombosit sayısı, risk faktörü olarak
tespit edildi.

Sonuç: Bu çalışma;
Diyabet, hiperlipidemi, LDL kolesterol düzeyi, non-HDL kolesterol düzeyi,
kalsiyum düzeyi, trombosit sayısı, aspirin direncini ön görmede
kullanılabilecek bir parametre olduğunu gösterdi. 

Anahtar Kelimeler

Aspirin direnci, akut koroner sendrom, risk faktörleri

Kaynakça

• 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. Antman EM, Braunwald E. ST-Elevation Myocardial İnfarction. In Zipes DP, Libby P, Braunwald E eds: A textbook of Cardiovascular Medicine. 2005; 7 th Edition:1141-66.
• 3. Patrono C, Baigent C, Hirsh J, Roth G, American College of Chest P. Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133(6 Suppl): 199S-233S.
• 4. Pedersen AK, FitzGerald GA. Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase. The New England journal of medicine. 1984;311(19):1206-11.
• 5. Antithrombotic Trialists C. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Bmj. 2002;324(7329):71-86.
• 6. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group. Lancet. 1990;336(8719):827-30.
• 7. Juul-Moller S, Edvardsson N, Jahnmatz B, Rosen A, Sorensen S, Omblus R. Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. The Swedish Angina Pectoris Aspirin Trial (SAPAT) Group. Lancet. 1992;340(8833):1421-5.
• 8. 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.
• 9. 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.
• 10. 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.
• 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. 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.
• 14. 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.
• 15. 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.
• 16. Barsky AA, Arora RR. Clopidogrel resistance: myth or reality? Journal of cardiovascular pharmacology and therapeutics. 2006;11(1):47-53.
• 17. 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.
• 18. Kim JD, Park CY, Ahn KJ, Cho JH, Choi KM, Kang JG, et al. Non-HDL cholesterol is an independent risk factor for aspirin resistance in obese patients with type 2 diabetes. Atherosclerosis. 2014;234(1):146-51.
• 19. Liu XF, Cao J, Fan L, Liu L, Li J, Hu GL, et al. Prevalence of and risk factors for aspirin resistance in elderly patients with coronary artery disease. Journal of geriatric cardiology : JGC. 2013;10(1):21-7.
• 20. 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.
• 21. Friend M, Vucenik I, Miller M. Research pointers: Platelet responsiveness to aspirin in patients with hyperlipidaemia. Bmj. 2003;326(7380):82-3.
• 22. Akoglu H, Agbaht K, Piskinpasa S, Falay MY, Dede F, Ozet G, et al. High frequency of aspirin resistance in patients with nephrotic syndrome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2012;27(4):1460-6.
• 23. Singla MK, Lahiri P, Mukhopadhyay P, Pandit K, Chaudhuri U, Chowdhury S. A study of aspirin resistance in type 2 diabetes. Journal of the Indian Medical Association. 2008;106(11):720, 2-3, 40.
• 24. Aksu H, Ozer O, Unal H, Hobikoglu G, Norgaz T, Buturak A, et al. Significance of mean platelet volume on prognosis of patients with and without aspirin resistance in settings of non-ST-segment elevated acute coronary syndromes. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2009;20(8):686-93.
• 25. Deniaud A, Sharaf el dein O, Maillier E, Poncet D, Kroemer G, Lemaire C, et al. Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis. Oncogene. 2008;27(3):285-99.