Variable platelet response to aspirin and clopidogrel is a well-known phenomenon in patients with coronary artery disease and ischemic cerebral stroke. The objective of the present study was to evaluate the frequency and possible risk factors of antiplatelet resistance in patients with cerebrovascular and cardiovascular diseases. The VerifyNow system was used to evaluate adenosine-5-diphosphate and platelet P2YI2 receptor function in patients with cerebrovascular and cardiovascular disease, who received dual antiplatelet therapy. Aspirin resistance was defined as aspirin reaction units (ARU) ≥ 550. Clopidogrel resistance was defined as Platelet Reaction Units (PRU) > 230. In the group of cerebrovascular diseases there were 13.2% (n = 27) patients with aspirin and 24.5% (n = 50) with clopidogrel resistance. However, in the cardiovascular group there were 20% (n = 9) aspirin and 11.1% (n = 5) clopidogrel resistant patients. In the cerebrovascular group, aspirin resistant patients had a lower triglyceride level (p = 0.001, r = 0.26) than aspirin sensitive patients. Clopidogrel resistant patients had a significantly higher level of glycated haemoglobin (HbA1C) (p = 0.016, r = 023), triglycerides (p = 0.033, r = 0.16) and lower level of high-density lipoproteins (p = 0.027, r = 0.16) than clopidogrel sensitive patients. In the cardiovascular group, patients who were resistant to aspirin had a significantly higher high-density lipoprotein level (p = 0.038, r = 0.31). No other factors differed significantly between the aspirin or clopidogrel resistant and sensitive patients in the cardiovascular group. Aspirin resistance was more common in patients with cardiovascular disease, and clopidogrel resistance in patients with cerebrovascular disease, although the difference was not significant. Our findings indicate that diabetes mellitus and an elevated level of lipoproteins could be risk factors for aspirin or clopidogrel resistance in patients with cerebrovascular diseases. Further studies should be conducted using larger patient cohorts with balanced groups of patients to investigate clinical aspects of antiplatelet resistance.
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Angiolillo D. J. Fernandez-Ortiz A. Bernardo E. Ramirez C. Sabate M. Jimenez-Quevedo P. Macaya C. (2005). Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes54 (8) 2430–2435.
Badimon L. Padró T. Vilahur G. (2012). Atherosclerosis platelets and thrombosis in acute ischaemic heart disease. Eur. Heart J. Acute Cardiovasc. Care1 (1) 60–74.
Balucani C. Barlinn K. Zivanovic Z. Parnetti L. Silvestrini M. Alexandrov A. V. (2010). Dual antiplatelet therapy in secondary prevention of ischemic stroke: A ghost from the past or a new frontier? Stroke Res. Treat. DOI 2010:427418.
Catella-Lawson F. Reilly M. P. Kapoor S. C. et al. (2001). Cyclooxygenase inhibitors and the antiplateleteffects of aspirin. New Engl. J. Med.345 1809–1817.
Feher G. Feher A. Pusch G. et al. (2010). Clinical importance of aspirin and clopidogrel resistance. World J. Cardiol. 2 (7) 171–186.
Feher G. Feher A. Pusch G. Lupkovics G. Szapary L. Papp E. (2009). The genetics of antiplatelet drug resistance. Clin. Genet.75 (1) 1–18.
Ferreira I. A. Mocking A. I. Feijge M. A. et al. (2006). Platelet inhibition by insulin is absent in type 2 diabetes mellitus. Arterioscler. Thromb. Vasc. Biol.26 417–422.
Fiolaki A. Katsanos A. H. Kyritsis A. P. Papadaki S. Kosmidou M. Moschonas I. C. Giannopoulos S. (2017). High on treatment platelet reactivity to aspirin and clopidogrel in ischemic stroke: A systematic review and meta-analysis. J. Neurol. Sci.376 112–116.
Freedman J. E. Hylek E. M. (2009). Clopidogrel genetics and drug responsiveness. New Engl. J. Med.360 (4) 411–413.
Goodman T. Ferro A. Sharma P. (2008). Pharmacogenetics of aspirin resistance: a comprehensive systematic review. Brit. J. Clin. Pharmacol. 66 (2) 222–232.
Gurbel P. A. Tantry U. S. (2007). Clopidogrel resistance? Thrombosis Res.120 (3) 311–321.
Karepov V. Tolpina G. Kuliczkowski W. Serebruany V. (2008). Plasma triglycerides as predictors of platelet responsiveness to aspirin in patients after first ischemic stroke. Cerebrovas. Dis.26 (3) 272–276.
Krasopoulos G. Brister S. J. BeattieW. S. Buchanan M. R. (2008). Aspirin “resistance” and risk of cardiovascular morbidity: Systematic review and meta-analysis. BMJ336 195–198.
Mansour K. Taher A. T. Musallam K. M. Alam S. (2009). Aspirin resistance. Adv. Hematol. 10.1155/2009/937352. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19960045 (accessed 15.05.2019).
Motovská Z. Varvarovský I. Ostádal P. (2017). ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Summary of the document prepared by the Czech Society of Cardiology. Cor et Vasa59 (6) e592–e612.
Poulsen T. S. Jorgensen B. Korsholm L. et al. (2017). Prevalence of aspirin resistance in patients with an evolving acute myocardial infarction. Thromb. Res.119 555–562.
Jones R. Arps K. Davis D. M. Blumenthal R. Martin S. S. (2018). Clinician Guide to the ABCs of Primary and Secondary Prevention of Atherosclerotic Cardiovascular Disease. Available from: https://www.acc.org/latest-in-cardiology/articles/2018/03/30/18/34/clinician-guide-to-the-abcs (accessed 15.05.2019).
Simon T. Verstuyft C. Mary-Krause M. et al. (2009). Genetic determinants of response to clopidogrel and cardiovascular events. New Engl. J. Med.360 (4) 363–375.
Snoep J. D. Hovens M. M. Eikenboom J. C. van der Bom J. G. Jukema J. W. Huisman M. V. (2007). Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: A systematic review and meta-analysis. Amer. Heart J. 154 221–231.
Wang C. B. Hu D. Y. Shi X. B. et al. (2006). Aspirin resistance in patients taking small dose of aspirin. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue18 219–223.
Wang T. H. Bhatt D. L. Topol E. J. (2005). Aspirin and clopidogrel resistance: An emerging clinical entity. Eur. Heart J.27 (6) 647–654.
Weber A. A. Zimmerman K. C. Meyer-Kirchrath J Schor K. (1999). Cyclooxygenase-2 in human platelets as a possible factor in aspirin resistance. Lancet353 900.
Wong K. S. L. Wang Y. Leng X. Mao C. Tang J. Bath P. M. W. Wang Y. (2013). Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack. Circulation128 (15) 1656–1666.
Zimmermann N. Wenk A. Kim U. Kienzle P. Weber A.-A. Gams E. Schror K. Hohlfeld T. (2003). Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery. Circulation108 542–547.