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KAROTİD ARTER STENTLEME YAPILAN HASTALARDA KLOPİDOGREL DİRENCİ VE ETKİLEYEN FAKTÖRLERİN DEĞERLENDİRİLMESİ

Year 2024, Volume: 57 Issue: 2, 59 - 63, 31.08.2024
https://doi.org/10.20492/aeahtd.1426008

Abstract

Amaç:
Karotid arter stentleme yapılan hastalarda peri ve postprosedüral süreçte trombotik komplikasyon riskini azaltmak amacıyla antiaggregan ilaçlar kullanılmaktadır. Hasta tedavi uyumuna rağmen amaçlanan tedavi etkisine ulaşılamayabilir ve bu durum sıklıkla antiagregan direnci ile ilişkilendirilir. Bu çalışmada, karotid arter stentleme yapılan hastalarda klopidogrel direnç sıklığı ve dirençle ilişkili olabilecek risk faktörlerinin belirlenmesi amaçlanmıştır.
Gereç ve Yöntem:
Çalışmada Başkent Üniversitesi Hastanesi’nde 2011-2023 yılları arasında nöroloji klinik yada polikliniklerinde karotid arter stentleme ile takip edilen hastaların verileri retrospektif olarak değerlendirildi. Düzensiz ilaç kullanımı olanlar çalışma dışı bırakıldı. Hastaların demografik özellikleri, aterosklerotik risk faktörleri, semptomları kaydedildi. Takip süreleri, periprosedüral süreçte görülen komplikasyonlar, takip restenoz, işlem sonrası serebrovasküler hastalık ve mortalite oranları saptandı. Stentleme yapılan taraf, darlık derecesi, kontralateral darlık varlığı kaydedildi. Kullanılan antiagregan ilaçlar, kullanım doz ve süreleri, klopidogrel direnç test sonuçları ve test zamanları kaydedildi. Direnç sıklığı ile demografik özellikler, komorbid durumlar, kullanılan ilaçlar ve kan tetkik sonuçları arasında ilişki olup olmadığı araştırıldı. Veriler SPSS paket programı ile analiz edildi. p< 0.05 istatiksel anlamlılık düzeyi olarak kabul edildi.
Bulgular:
Toplam 138 hastanın yaş ortalamaları 68.91±8,66 yıldı ve %71.7’si erkek cinsiyetindeydi. Hastaların %52.2’ sinde sağ karotid arter darlığı bulunmaktaydı. Darlık dereceleri değerlendirildiğinde, 65 hastada (%47.1) ≥ %90 darlık saptandı. 103 hastada (%74.6) semptomatik karotid arter darlığı nedeniyle işlem planlanmıştı. 87 hastada (%63.3) ADP testi yapılmıştı. Klopidogrel kullanan hastaların %17.2’sinde ilaç direnci gözlendi. Klopidogrel direnci kadın hastalarda erkeklere oranla istatiksel olarak anlamlı oranda yüksek saptandı (p<0.05). Yaş, aterosklerotik hastalıkları ve eş zamanlı kullanılan ilaçlar ile klopidogrel direnci arasında istatiksel anlamlı fark saptanmadı. Hastalarda direnç testi bakılma zamanı ile direnç saptanma oranları arasında istatiksel fark izlenmedi.
Sonuç:
Nörovasküler stent hastalarında antiagrean ilaç direncine yönelik veriler yeterli değildir. Bu hastalarda antiagregan ilaç etkisinin ve direncinin belirlenmesi direnç izlenen hasta grubunda stentle ilişkili komplikasyonların ve serebrovasküler olayların önlenmesi için değerli olabilir.

Ethical Statement

BU PROJE BAŞKENT ÜNİVERSİTESİ TIP VE SAĞLIK BİLİMLERİ ARAŞTIRMA KURULU TARAFINDAN ONAYLANMIŞTIR . (PROJE NO : 23/450)

References

  • 1. Collette SL, Bokkers RPH, Dierckx RAJO, van der Laan MJ, Zeebregts CJ, Uyttenboogaart M. Clinical importance of testing for clopidogrel resistance in patients undergoing carotid artery stenting- a systematic review. Ann Transl Med. 2021;9(14):1211.
  • 2. Prabhakaran S, Wells KR, Lee VH, Flaherty CA, Lopes DK. Prevalence and risk factors for aspirin and clopidogrel resistance in cerebrovascular stenting. AJNR Am J Neuroradiol. 2008;29(2):281- 5.
  • 3. Barutçuoğlu B. Antitrombositik Tedavi İzleminde Trombosit Fonksiyon Testleri. Türk Klinik Biyokimya Derg. 2016;14(2):144-55.
  • 4. Yılmaz Can F, Çetin BN. Karotis renkli Doppler ultrasonografide anlamlı darlığı olan hastaların asetilsalisilik asit ve klopidogrel direnç sonuçlarının değerlendirilmesi. Türk Beyin Damar Hast Der. 2022;28(1):46-53.
  • 5. Kim H, Lee HK, Han K, Jeon HK. Prevalence and risk factors for aspirin and clopidogrel resistance in patients with coronary artery disease or ischemic cerebrovascular disease. Ann Clin Lab Sci. 2009;39(3):289-94.
  • 6. Fifi JT, Brockington C, Narang J, Leesch W, Ewing SL, Bennet H,et al. Clopidogrel resistance is associated with thromboembolic complications in patients undergoing neurovascular stenting. AJNR Am J Neuroradiol. 2013;34(4):716-20.
  • 7. Ryu DS, Hong CK, Sim YS, Kim CH, Jung JY, Joo JY. Anti- platelet drug resistance in the prediction of thromboembolic complications after neurointervention. J Korean Neurosurg Soc. 2010;48(4):319-24.
  • 8. Song TJ, Suh SH, Min PK, Kim DJ, Kim BM, Heo JH, et al. The influence of anti-platelet resistance on the development of cerebral ischemic lesion after carotid artery stenting. Yonsei Med J. 2013;54(2):288-94.
  • 9. Sorkin GC, Dumont TM, Wach MM, Eller JL, Mokin M, Natarajan SK, et al. Carotid artery stenting outcomes: do they correlate with antiplatelet response assays? J Neurointerv Surg. 2014;6(5):373-8.
  • 10. Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol. 2005;45(8):1157- 64.
  • 11. Mazzaccaro D, Giannetta M, Ranucci M, Righini P, Di Dedda U, Baryshnikova E, et al. Clopidogrel Resistance and Ticagrelor Replacement in Dual Antiplatelet Therapy for Carotid Artery Stenting. Ann Vasc Surg. 2023;90:128-36.
  • 12. Müller-Schunk S, Linn J, Peters N, Spannagl M, Deisenberg M, Brückmann H, et al. Monitoring of clopidogrel-related platelet inhibition: correlation of nonresponse with clinical outcome in supra- aortic stenting. AJNR Am J Neuroradiol. 2008;29(4):786-91.
  • 13. Aksoy F, Baş HA, Bağci A, Uysal BA, Aksoy S, Varol E, et al. Isparta ve çevresinde klopidogrel direncinin araştırılması. Med J SDU. 2019;26(4):416-22.
  • 14. 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. Vasc Health Risk Manag. 2013;9:187-93.
  • 15. Nakagawa I, Park HS, Yokoyama S, Wada T, Hironaka Y, Motoyama Y, et al. Influence of Diabetes Mellitus and Cigarette Smoking on Variability of the Clopidogrel-Induced Antiplatelet Effect and Efficacy of Active Management of the Target P2Y12 Reaction Unit Range in Patients Undergoing Neurointerventional Procedures. J Stroke Cerebrovasc Dis. 2016;25(1):163-71.
  • 16. 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;124(5):588-91.
  • 17. Desai NR, Mega JL, Jiang S, Cannon CP, Sabatine MS. Interaction between cigarette smoking and clinical benefit of clopidogrel. Interaction between cigarette smoking and clinical benefit of clopidogrel. J Am Coll Cardiol. 2009;53(15):1273-8.
  • 18. Li L, Han J, Li H, 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.
  • 19. Flechtenmacher N, Kämmerer F, Dittmer R, Budde U, Michels P, Röther J, et al. Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry, VerifyNow, and the Multiplate. AJNR Am J Neuroradiol. 2015;36(10):1953-8.

EVALUATION OF CLOPIDOGREL RESISTANCE AND AFFECTING FACTORS IN PATIENTS UNDERGOING CAROTID ARTERY STENTING

Year 2024, Volume: 57 Issue: 2, 59 - 63, 31.08.2024
https://doi.org/10.20492/aeahtd.1426008

Abstract

Aim:
Antiaggregant drugs are used to reduce the risk of thrombotic complications in the peri- and postprocedural period in patients undergoing carotid artery stenting. Despite patient compliance with treatment, the intended treatment effect may not be achieved, and this is often associated with antiaggregant resistance. This study aimed to determine the frequency of clopidogrel resistance and risk factors that may be associated with resistance in patients undergoing carotid artery stenting.
Material and Method:
In the study, the data of patients who were followed up with carotid artery stenting in neurology clinics or outpatient clinics at Başkent University Hospital between 2011 and 2023 were evaluated retrospectively. Those who used irregular medication were excluded from the study. The demographic characteristics, atherosclerotic risk factors, and symptoms of the patients were recorded. Follow-up periods, periprocedural complications, follow-up restenosis, post-procedural cerebrovascular disease and mortality rates were determined. The side of stenting, the degree of stenosis, and the presence of contralateral stenosis were recorded. Antiaggregant drugs used, dosage and duration of use, clopidogrel resistance test results and test times were recorded. The relationship between the frequency of resistance and demographic characteristics, comorbid conditions, medications used and blood test results were evaluated. The data were analyzed with the SPSS program. p< 0.05 was accepted as the level of statistical significance.
Results:
The average age of a total of 138 patients was 68.91±8.66 years and 71.7% were male. 52.2% of the patients had right carotid artery stenosis. ≥ 90% stenosis was detected in 65 patients (47.1%). The procedure was planned in 103 patients (74.6%) due to symptomatic carotid artery stenosis. ADP test was performed in 87 patients (63.3%). Drug resistance was observed in 17.2% of patients using clopidogrel. Clopidogrel resistance was found to be statistically significantly higher in female patients than in males (p<0.05). No statistically significant difference was found between age, atherosclerotic diseases, concurrent medications and clopidogrel resistance. No statistical difference was observed between the time of testing and the resistance detection rates in the patients.
Conclusion:
There are insufficient data on antiplatelet drug resistance in neurovascular stent patients. Determining the antiplatelet drug effect and resistance in these patients may be valuable to prevent stent-related complications and cerebrovascular events in the patient group with resistance.

References

  • 1. Collette SL, Bokkers RPH, Dierckx RAJO, van der Laan MJ, Zeebregts CJ, Uyttenboogaart M. Clinical importance of testing for clopidogrel resistance in patients undergoing carotid artery stenting- a systematic review. Ann Transl Med. 2021;9(14):1211.
  • 2. Prabhakaran S, Wells KR, Lee VH, Flaherty CA, Lopes DK. Prevalence and risk factors for aspirin and clopidogrel resistance in cerebrovascular stenting. AJNR Am J Neuroradiol. 2008;29(2):281- 5.
  • 3. Barutçuoğlu B. Antitrombositik Tedavi İzleminde Trombosit Fonksiyon Testleri. Türk Klinik Biyokimya Derg. 2016;14(2):144-55.
  • 4. Yılmaz Can F, Çetin BN. Karotis renkli Doppler ultrasonografide anlamlı darlığı olan hastaların asetilsalisilik asit ve klopidogrel direnç sonuçlarının değerlendirilmesi. Türk Beyin Damar Hast Der. 2022;28(1):46-53.
  • 5. Kim H, Lee HK, Han K, Jeon HK. Prevalence and risk factors for aspirin and clopidogrel resistance in patients with coronary artery disease or ischemic cerebrovascular disease. Ann Clin Lab Sci. 2009;39(3):289-94.
  • 6. Fifi JT, Brockington C, Narang J, Leesch W, Ewing SL, Bennet H,et al. Clopidogrel resistance is associated with thromboembolic complications in patients undergoing neurovascular stenting. AJNR Am J Neuroradiol. 2013;34(4):716-20.
  • 7. Ryu DS, Hong CK, Sim YS, Kim CH, Jung JY, Joo JY. Anti- platelet drug resistance in the prediction of thromboembolic complications after neurointervention. J Korean Neurosurg Soc. 2010;48(4):319-24.
  • 8. Song TJ, Suh SH, Min PK, Kim DJ, Kim BM, Heo JH, et al. The influence of anti-platelet resistance on the development of cerebral ischemic lesion after carotid artery stenting. Yonsei Med J. 2013;54(2):288-94.
  • 9. Sorkin GC, Dumont TM, Wach MM, Eller JL, Mokin M, Natarajan SK, et al. Carotid artery stenting outcomes: do they correlate with antiplatelet response assays? J Neurointerv Surg. 2014;6(5):373-8.
  • 10. Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol. 2005;45(8):1157- 64.
  • 11. Mazzaccaro D, Giannetta M, Ranucci M, Righini P, Di Dedda U, Baryshnikova E, et al. Clopidogrel Resistance and Ticagrelor Replacement in Dual Antiplatelet Therapy for Carotid Artery Stenting. Ann Vasc Surg. 2023;90:128-36.
  • 12. Müller-Schunk S, Linn J, Peters N, Spannagl M, Deisenberg M, Brückmann H, et al. Monitoring of clopidogrel-related platelet inhibition: correlation of nonresponse with clinical outcome in supra- aortic stenting. AJNR Am J Neuroradiol. 2008;29(4):786-91.
  • 13. Aksoy F, Baş HA, Bağci A, Uysal BA, Aksoy S, Varol E, et al. Isparta ve çevresinde klopidogrel direncinin araştırılması. Med J SDU. 2019;26(4):416-22.
  • 14. 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. Vasc Health Risk Manag. 2013;9:187-93.
  • 15. Nakagawa I, Park HS, Yokoyama S, Wada T, Hironaka Y, Motoyama Y, et al. Influence of Diabetes Mellitus and Cigarette Smoking on Variability of the Clopidogrel-Induced Antiplatelet Effect and Efficacy of Active Management of the Target P2Y12 Reaction Unit Range in Patients Undergoing Neurointerventional Procedures. J Stroke Cerebrovasc Dis. 2016;25(1):163-71.
  • 16. 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;124(5):588-91.
  • 17. Desai NR, Mega JL, Jiang S, Cannon CP, Sabatine MS. Interaction between cigarette smoking and clinical benefit of clopidogrel. Interaction between cigarette smoking and clinical benefit of clopidogrel. J Am Coll Cardiol. 2009;53(15):1273-8.
  • 18. Li L, Han J, Li H, 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.
  • 19. Flechtenmacher N, Kämmerer F, Dittmer R, Budde U, Michels P, Röther J, et al. Clopidogrel Resistance in Neurovascular Stenting: Correlations between Light Transmission Aggregometry, VerifyNow, and the Multiplate. AJNR Am J Neuroradiol. 2015;36(10):1953-8.
There are 19 citations in total.

Details

Primary Language Turkish
Subjects Neurology and Neuromuscular Diseases
Journal Section Original research article
Authors

İlkin İyigündoğdu 0000-0001-7860-040X

Bengisu Şahin 0009-0007-1014-6686

Eda Derle 0000-0003-2122-1016

Ufuk Can 0000-0001-8689-417X

Publication Date August 31, 2024
Submission Date February 22, 2024
Acceptance Date August 30, 2024
Published in Issue Year 2024 Volume: 57 Issue: 2

Cite

AMA İyigündoğdu İ, Şahin B, Derle E, Can U. KAROTİD ARTER STENTLEME YAPILAN HASTALARDA KLOPİDOGREL DİRENCİ VE ETKİLEYEN FAKTÖRLERİN DEĞERLENDİRİLMESİ. Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi. August 2024;57(2):59-63. doi:10.20492/aeahtd.1426008