Thromboelastographic and Gene Polymorphism Bimodality Detection for Dual Antiplatelet Aggregation Therapy in Individuals with Clopidogrel-resistant Symptomatic Intracranial Artery Stenosis


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Abstract

Background:Recent research indicates that clopidogrel resistance is connected with a patient's future ischemia risk, hence increasing the likelihood of recurrent ischemic cerebrovascular disease. Thromboelastographic and clopidogrel gene polymorphism testing can be used to see how a person responds to antiplatelet therapy and change the treatment plan accordingly. This may be a good way to make antiplatelet aggregation therapy more effective and safer

Objective:The objective of this study was to investigate the efficacy of dual antiplatelet aggregation therapy in patients with symptomatic intracranial large artery stenosis being resistant to clopidogrel tablets. The thromboelastographic and gene polymorphism bimodality detection techniques were used to analyze the clopidogrel resistance influencing factors.

Methods:89 patients with symptomatic intracranial large arterial stenosis who were admitted to our hospital from February 2021 to February 2022 were selected, classified as large artery atherosclerotic type by TOAST, and confirmed as having severe intracranial large arterial stenosis (70 % to 99 %) by magnetic resonance angiography (MRA), computed tomographic angiography (CTA), and digital subtraction angiography (DSA). All patients were treated with dual antiplatelet therapy with aspirin and clopidogrel, and thromboelastography and clopidogrel gene polymorphism were monitored 1 week later.

Results:44 of 89 patients were clopidogrel-resistant. Among 44 patients, 20 were ticagrelorresistant and 24 were cilostazol-resistant. Clopidogrel had a resistance rate of 49.4%. The recurrence of ischemic cerebrovascular disease in the three groups was statistically significant (P(<0.05) after 3 months of follow-up treatment, but bleeding (intracranial, gastrointestinal, respiratory, urinary, and mucocutaneous) and dyspnea were not. The clopidogrel-resistant group had a higher number of females, as well as higher levels of hypertension, diabetes, and platelet count than the sensitive group (P(<0.05), but there was no significant difference in age, smoking, alcohol consumption, previous stroke, glycosylated haemoglobin, creatinine, or low-density cholesterol.

Conclusion:Using thromboelastographic and gene polymorphism bimodality detection, we found switching to ticagrelor antiplatelet aggregation therapy as better than switching to cilostazol in patients with symptomatic intracranial large artery stenosis being resistant to clopidogrel tablets. The results may be biased due to the study being a single-centre study and having a limited sample size.

About the authors

Longlong Liu

Department of Emergency, Boxing People's Hospital

Author for correspondence.
Email: info@benthamscience.net

Yan Li

Department of Neurology,, Binzhou People's Hospital

Email: info@benthamscience.net

Ying Li

Department of Emergency, Binzhou People's Hospital

Email: info@benthamscience.net

References

  1. Sun, T.; Chen, S.; Wu, K.; Sun, M.; Zhang, X.; You, C. Trends in incidence and mortality of stroke in China From 1990 to 2019. Front. Neurol., 2021, 12, 759221. doi: 10.3389/fneur.2021.759221 PMID: 34880825
  2. Liu, M.; Yan, M.; Guo, Y.; Xie, Z.; Li, R.; Li, J.; Ren, C.; Ji, X.; Guo, X. Acute ischemic stroke at high altitudes in China: Early onset and severe manifestations. Cells, 2021, 10(4), 809. doi: 10.3390/cells10040809 PMID: 33916503
  3. Flusty, B.; de Havenon, A.; Prabhakaran, S.; Liebeskind, D.S.; Yaghi, S. Intracranial atherosclerosis treatment. Stroke, 2020, 51(3), e49-e53. doi: 10.1161/STROKEAHA.119.028528 PMID: 32078441
  4. Wang, Y.; Zhao, X.; Liu, L.; Soo, Y.O.Y.; Pu, Y.; Pan, Y.; Wang, Y.; Zou, X.; Leung, T.W.H.; Cai, Y.; Bai, Q.; Wu, Y.; Wang, C.; Pan, X.; Luo, B.; Wong, K.S.L.; Zhang, X.; Sun, X.; Yu, L.; Guo, M.; Ma, Q.; Xiao, B.; Zhang, L.; Zhang, Z.; Xu, A.; Li, J.; Lin, J.; Xing, C.; Xu, Y.; Zheng, R.; Han, Z.; Yuan, X.; Cui, W.; Zou, Y.; Yan, H. Prevalence and outcomes of symptomatic intracranial large artery stenoses and occlusions in China: The Chinese Intracranial Atherosclerosis (CICAS) Study. Stroke, 2014, 45(3), 663-669. doi: 10.1161/STROKEAHA.113.003508 PMID: 24481975
  5. Kleindorfer, D.O.; Towfighi, A.; Chaturvedi, S.; Cockroft, K.M.; Gutierrez, J.; Lombardi-Hill, D.; Kamel, H.; Kernan, W.N.; Kittner, S.J.; Leira, E.C.; Lennon, O.; Meschia, J.F.; Nguyen, T.N.; Pollak, P.M.; Santangeli, P.; Sharrief, A.Z.; Smith, S.C., Jr; Turan, T.N.; Williams, L.S. 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline from the American heart association/american stroke association. Stroke, 2021, 52(7), e364-e467. doi: 10.1161/STR.0000000000000375 PMID: 34024117
  6. Mărginean, A.; Bănescu, C.; Scridon, A.; Dobreanu, M. Anti-platelet therapy resistance – concept, mechanisms and platelet function tests in intensive care facilities. J. Crit. Care Med., 2016, 2(1), 6-15. doi: 10.1515/jccm-2015-0021 PMID: 29967831
  7. Oxley, T.J.; Dowling, R.J.; Mitchell, P.J.; Davis, S.; Yan, B. Antiplatelet resistance and thromboembolic complications in neurointerventional procedures. Front. Neurol., 2011, 2, 83. doi: 10.3389/fneur.2011.00083 PMID: 22363312
  8. Uchiyama, S. Clopidogrel resistance: Identifying and overcoming a barrier to effective antiplatelet treatment. Cardiovasc. Ther., 2011, 29(6), e100-e111. doi: 10.1111/j.1755-5922.2010.00202.x PMID: 21883990
  9. Akkaif, M.A.; Daud, N.A.A.; Sha’aban, A.; Ng, M.L.; Abdul Kader, M.A.S.; Noor, D.A.M.; Ibrahim, B. The role of genetic polymorphism and other factors on clopidogrel resistance (CR) in an Asian Population with Coronary Heart Disease (CHD). Molecules, 2021, 26(7), 1987. doi: 10.3390/molecules26071987 PMID: 33915807
  10. Chen, K.N.; Wang, Y.L. Chinese expert consensus on endovascular treatment of symptomatic atherosclerotic nonacute intracranial large artery occlusion. Chin. J. Neurol., 2018, 13(11), 1166-1181.
  11. Fiolaki, A.; Katsanos, A.H.; Kyritsis, A.P.; Papadaki, S.; Kosmidou, M.; Moschonas, I.C.; Tselepis, A.D.; Giannopoulos, S. High on treatment platelet reactivity to aspirin and clopidogrel in ischemic stroke: A systematic review and meta-analysis. J. Neurol. Sci., 2017, 376, 112-116. doi: 10.1016/j.jns.2017.03.010 PMID: 28431593
  12. Fu, H.; Hu, P.; Ma, C.; Peng, F.; He, Z. Association of clopidogrel high on-treatment reactivity with clinical outcomes and gene polymorphism in acute ischemic stroke patients. Medicine, 2020, 99(15), e19472. doi: 10.1097/MD.0000000000019472 PMID: 32282698
  13. Kinsella, J.A.; Tobin, W.O.; Cox, D.; Coughlan, T.; Collins, R.; O’Neill, D.; Murphy, R.P.; McCabe, D.J.H. Prevalence of ex vivo high on-treatment platelet reactivity on antiplatelet therapy after transient ischemic attack or ischemic stroke on the PFA-100(®) and VerifyNow (®). J. Stroke Cerebrovasc. Dis., 2013, 22(7), e84-e92. doi: 10.1016/j.jstrokecerebrovasdis.2012.07.012 PMID: 22981273
  14. Wu, Z.; Liu, A.F.; Zhou, J.; Zhang, Y.; Wang, K.; Li, C.; Qiu, H.; Jiang, W.J. The safety of triple antiplatelet therapy under thromboelastography guidance in patients undergoing stenting for ischemic cerebrovascular disease. J. Neurointerv. Surg., 2019, 11(4), 352-356. doi: 10.1136/neurintsurg-2018-013987 PMID: 30100558
  15. Kumar, S.; Sharma, B.; Bhardwaj, T.R.; Singh, R.K. Design, synthesis and studies on novel polymeric prodrugs of erlotinib for colon drug delivery. Anticancer. Agents Med. Chem., 2021, 21(3), 383-392. doi: 10.2174/1871520620666200811124013 PMID: 32781967
  16. Sehajpal, S.; Prasad, D.N.; Singh, R.K. Novel ketoprofen–antioxidants mutual codrugs as safer nonsteroidal anti‐inflammatory drugs: Synthesis, kinetic and pharmacological evaluation. Arch. Pharm., 2019, 352(7), 1800339. doi: 10.1002/ardp.201800339 PMID: 31231875
  17. Singh, R.K.; Prasad, D.N.; Bhardwaj, T.R. Synthesis in vitro/in vivo evaluation and in silico physicochemical study of prodrug approach for brain targeting of alkylating agent. Med. Chem. Res., 2013, 22(11), 5324-5336. doi: 10.1007/s00044-013-0537-0
  18. Zhong, S.L.; Han, Y.L.; Chen, J.Y. Interpretation of genotyping guidelines for individualized antiplatelet therapy with clopidogrel. Chin. J. Prac. Int. Med., 2015, 35(01), 38-41.
  19. Brown, S.A.; Pereira, N. Pharmacogenomic impact of CYP2C19 variation on clopidogrel therapy in precision cardiovascular medicine. J. Pers. Med., 2018, 8(1), 8. doi: 10.3390/jpm8010008 PMID: 29385765
  20. Brandt, J.T.; Close, S.L.; Iturria, S.J.; Payne, C.D.; Farid, N.A.; Ernest, C.S., II; Lachno, D.R.; Salazar, D.; Winters, K.J. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J. Thromb. Haemost., 2007, 5(12), 2429-2436. doi: 10.1111/j.1538-7836.2007.02775.x PMID: 17900275
  21. Yi, X.; Wang, Y.; Lin, J.; Cheng, W.; Zhou, Q.; Wang, C. Interaction of CYP2C19, P2Y12, and GPIIIa variants associates with efficacy of clopidogrel and adverse events on patients with ischemic stroke. Clin. Appl. Thromb. Hemost., 2017, 23(7), 761-768. doi: 10.1177/1076029616648408 PMID: 27233747
  22. Zhuo, Z.L.; Xian, H.P.; Long, Y.; Liu, C.; Sun, Y.Y.; Ma, Y.T.; Gao, H.; Zhao, J.Z.; Zhao, X.T. Association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance in clopidogrel-treated Chinese patients. Anatol. J. Cardiol., 2018, 19(2), 123-129. doi: 10.14744/AnatolJCardiol.2017.8097 PMID: 29350207
  23. Karaźniewicz-Łada, M.; Krzyżańska, D.; Danielak, D.; Rzeźniczak, J.; Główka, F.; Słomczyński, M.; Burchardt, P. Impact of genetic variants of selected cytochrome P450 isoenzymes on pharmacokinetics and pharmacodynamics of clopidogrel in patients co-treated with atorvastatin or rosuvastatin. Eur. J. Clin. Pharmacol., 2020, 76(3), 419-430. doi: 10.1007/s00228-019-02822-x PMID: 31897532
  24. Zhang, L.M.; Wang, D.Z.; Sun, Y.H. Clinical characteristics and risk factors of clopidogrel resistance in patients with ischemic cerebrovascular disease after intracranial artery stenting. China Comp. Clin., 2021, 37(1), 7-11.
  25. González, A.; Moniche, F.; Cayuela, A.; García-Lozano, J.R.; Torrecillas, F.; Escudero-Martínez, I.; Gonzalez-Marcos, J.R.; Mayol, A.; Montaner, J. Effect of CYP2C19 polymorphisms on the platelet response to clopidogrel and influence on the effect of high versus standard dose clopidogrel in carotid artery stenting. Eur. J. Vasc. Endovasc. Surg., 2016, 51(2), 175-186. doi: 10.1016/j.ejvs.2015.09.020 PMID: 26526111
  26. Malhotra, K.; Goyal, N.; Kasunich, A.S.; Sheth, S.A.; Katsanos, A.H.; Alexandrov, A.V.; Tsivgoulis, G. Ticagrelor for stroke prevention in patients with vascular risk factors: A systematic review and meta-analysis. J. Neurol. Sci., 2018, 390, 212-218. doi: 10.1016/j.jns.2018.05.001 PMID: 29801891
  27. Bhogal, P.; Brouwer, P.A.; Makalanda, H.L.D. Cilostazol: An antiplatelet agent for the neurointerventionist? J. Neurointerv. Surg., 2016, 8(2), 208-209. doi: 10.1136/neurintsurg-2014-011570 PMID: 25526917
  28. Nakagawa, I.; Wada, T.; Park, H.S.; Nishimura, F.; Yamada, S.; Nakagawa, H.; Kichikawa, K.; Nakase, H. Platelet inhibition by adjunctive cilostazol suppresses the frequency of cerebral ischemic lesions after carotid artery stenting in patients with carotid artery stenosis. J. Vasc. Surg., 2014, 59(3), 761-767. doi: 10.1016/j.jvs.2013.09.011 PMID: 24239116
  29. 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. doi: 10.3390/ijms21176408 PMID: 32899176
  30. Greer, D.M. Aspirin and antiplatelet agent resistance: Implications for prevention of secondary stroke. CNS Drugs, 2010, 24(12), 1027-1040. doi: 10.2165/11539160-0000000000-00000 PMID: 20932071
  31. Sorkin, G.C.; Dumont, T.M.; Wach, M.M.; Eller, J.L.; Mokin, M.; Natarajan, S.K.; Baxter, M.S.; Snyder, K.V.; Levy, E.I.; Hopkins, L.N.; Siddiqui, A.H. Carotid artery stenting outcomes: Do they correlate with antiplatelet response assays? J. Neurointerv. Surg., 2014, 6(5), 373-378. doi: 10.1136/neurintsurg-2013-010771 PMID: 23794673

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