The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Detection of Clopidogrel Hyporesponsiveness Using a Point-of-Care Assay and the Impact of Additional Cilostazol Administration after Coronary Stent Implantation in Diabetic Patients

  • Yang, Tae-Hyun (Division of Cardiology, Department of Internal Medicine & Cardiovascular Research Institute, Busan Paik Hospital, Inje University College of Medicine) ;
  • Kim, Doo-Il (Division of Cardiology, Department of Internal Medicine & Cardiovascular Research Institute, Haeundae Paik Hospital, Inje University College of Medicine) ;
  • Kim, Dong-Kie (Division of Cardiology, Department of Internal Medicine & Cardiovascular Research Institute, Haeundae Paik Hospital, Inje University College of Medicine) ;
  • Jang, Jae-Sik (Division of Cardiology, Department of Internal Medicine & Cardiovascular Research Institute, Busan Paik Hospital, Inje University College of Medicine) ;
  • Kim, Ung (Division of Cardiology, Department of Internal Medicine & Cardiovascular Research Institute, Haeundae Paik Hospital, Inje University College of Medicine) ;
  • Seol, Sang-Hoon (Division of Cardiology, Department of Internal Medicine & Cardiovascular Research Institute, Haeundae Paik Hospital, Inje University College of Medicine) ;
  • Kim, Dae-Kyeong (Division of Cardiology, Department of Internal Medicine & Cardiovascular Research Institute, Busan Paik Hospital, Inje University College of Medicine) ;
  • Hong, Geu-Ru (Yeungnam University Medical Center) ;
  • Park, Jong-Seon (Yeungnam University Medical Center) ;
  • Shin, Dong-Gu (Yeungnam University Medical Center) ;
  • Kim, Young-Jo (Yeungnam University Medical Center) ;
  • Cho, Yun-Kyeong (Keimyung University Dongsan Medical Center) ;
  • Nam, Chang-Wook (Keimyung University Dongsan Medical Center) ;
  • Hur, Seung-Ho (Keimyung University Dongsan Medical Center) ;
  • Kim, Kwon-Bae (Keimyung University Dongsan Medical Center) ;
  • Kim, Dong-Soo (Division of Cardiology, Department of Internal Medicine & Cardiovascular Research Institute, Busan Paik Hospital, Inje University College of Medicine)
  • Published : 2011.06.01
⟨ Previous Next ⟩

Abstract

Background/Aims: Impaired responsiveness to clopidogrel is common in patients with type 2 diabetes mellitus (DM). The aim of this study was to evaluate the clinical application of a point-of-care assay to detect impaired responsiveness to clopidogrel after coronary stent implantation in patients with type 2 DM. Methods: We measured P2Y12 reaction units (PRU) with the VerifyNow point-of-care assay in 544 consecutive patients undergoing dual or triple (i.e., dual plus cilostazol) anti-platelet therapy after coronary stent implantation. High platelet reactivity (HPR) was defined as a PRU value ${\geq}$ 240. Results: The mean PRU values were $233.5\;{\pm}\;83.2\;and\;190.3\;{\pm}\;85.5$ in patients undergoing dual or triple anti-platelet therapy, respectively (p < 0.001). Patients with DM manifested higher post treatment PRU values ($238.3\;{\pm}\;82.4\;vs.\;210.8\;{\pm}\;86.8$, p = 0.001) and a higher frequency of HPR (44.8% vs. 31.0%, p = 0.003) as compared to patients without DM. We also found that higher PRU values and a higher frequency of HPR were present in patients with DM who were undergoing both triple and dual anti-platelet therapy. However, the higher post-treatment PRU values observed in patients with DM decreased with triple anti-platelet therapy ($219.4\;{\pm}\;82.5\;vs.\;247.9\;{\pm}\;81.1$, p = 0.044). Conclusions: A point-of-care assay can detect elevated platelet reactivity and impaired responsiveness to clopidogrel in patients with type 2 DM. The addition of cilostazol to dual anti-platelet therapy may decrease post-treatment PRU values in patients with type 2 DM.

Keywords

References

  1. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease: the Bypass Angioplasty Revascularization Investigation (BARI) Investigators. N Engl J Med 1996;335:217-225. https://doi.org/10.1056/NEJM199607253350401
  2. Mak KH, Moliterno DJ, Granger CB, et al. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. J Am Coll Cardiol 1997;30:171-179. https://doi.org/10.1016/S0735-1097(97)00118-6
  3. Malmberg K, Yusuf S, Gerstein HC, et al. Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry. Circulation 2000;102:1014-1019. https://doi.org/10.1161/01.CIR.102.9.1014
  4. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126-2130. https://doi.org/10.1001/jama.293.17.2126
  5. Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL. Platelet dysfunction in type 2 diabetes. Diabetes Care 2001;24:1476-1485. https://doi.org/10.2337/diacare.24.8.1476
  6. Ferroni P, Basili S, Falco A, Davi G. Platelet activation in type 2 diabetes mellitus. J Thromb Haemost 2004;2:1282-1291. https://doi.org/10.1111/j.1538-7836.2004.00836.x
  7. Colwell JA, Nesto RW. The platelet in diabetes: focus on prevention of ischemic events. Diabetes Care 2003;26:2181-2188. https://doi.org/10.2337/diacare.26.7.2181
  8. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes 2005;54:2430-2435. https://doi.org/10.2337/diabetes.54.8.2430
  9. Lee BK, Lee SW, Park SW, et al. Effects of triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol) on platelet aggregation and P-selectin expression in patients undergoing coronary artery stent implantation. Am J Cardiol 2007;100:610-614. https://doi.org/10.1016/j.amjcard.2007.03.070
  10. Ahn JC, Song WH, Kwon JA, et al. Effects of cilostazol on platelet activation in coronary stenting patients who already treated with aspirin and clopidogrel. Korean J Intern Med 2004;19:230-236.
  11. Patti G, Nusca A, Mangiacapra F, Gatto L, D'Ambrosio A, Di Sciascio G. Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study. J Am Coll Cardiol 2008;52:1128-1133. https://doi.org/10.1016/j.jacc.2008.06.038
  12. Marcucci R, Gori AM, Paniccia R, et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation 2009;119:237-242. https://doi.org/10.1161/CIRCULATIONAHA.108.812636
  13. Angiolillo DJ, Bernardo E, Ramírez C, et al. Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment. J Am Coll Cardiol 2006;48:298-304. https://doi.org/10.1016/j.jacc.2006.03.038
  14. Ferreira IA, Mocking AI, Feijge MA, et al. Platelet inhibition by insulin is absent in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol 2006;26:417-422.
  15. 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. Am Heart J 2007;154:221-231. https://doi.org/10.1016/j.ahj.2007.04.014
  16. Buonamici P, Marcucci R, Migliorini A, et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol 2007;49:2312-2317. https://doi.org/10.1016/j.jacc.2007.01.094
  17. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004;109:3171-3175. https://doi.org/10.1161/01.CIR.0000130846.46168.03
  18. Hochholzer W, Trenk D, Bestehorn HP, et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol 2006;48:1742-1750. https://doi.org/10.1016/j.jacc.2006.06.065
  19. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003;107:2908-2913. https://doi.org/10.1161/01.CIR.0000072771.11429.83
  20. Price MJ, Coleman JL, Steinhubl SR, Wong GB, Cannon CP, Teirstein PS. Onset and offset of platelet inhibition after high-dose clopidogrel loading and standard daily therapy measured by a point-of-care assay in healthy volunteers. Am J Cardiol 2006;98:681-684. https://doi.org/10.1016/j.amjcard.2006.03.054
  21. Gurbel PA, Becker RC, Mann KG, Steinhubl SR, Michelson AD. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 2007;50:1822-1834. https://doi.org/10.1016/j.jacc.2007.07.051
  22. Michelson AD. Platelet function testing in cardiovascular diseases. Circulation 2004;110:e489-e493. https://doi.org/10.1161/01.CIR.0000147228.29325.F9
  23. van Werkum JW, van der Stelt CA, Seesing TH, Hackeng CM, ten Berg JM. A head-to-head comparison between the VerifyNow P2Y12 assay and light transmittance aggregometry for monitoring the individual platelet response to clopidogrel in patients undergoing elective percutaneous coronary intervention. J Thromb Haemost 2006;4:2516-2518. https://doi.org/10.1111/j.1538-7836.2006.02187.x
  24. Malinin A, Pokov A, Swaim L, Kotob M, Serebruany V. Validation of a VerifyNow-P2Y12 cartridge for monitoring platelet inhibition with clopidogrel. Methods Find Exp Clin Pharmacol 2006;28:315-322. https://doi.org/10.1358/mf.2006.28.5.990205
  25. Paniccia R, Antonucci E, Gori AM, et al. Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients. J Thromb Haemost 2007;5:1839-1847. https://doi.org/10.1111/j.1538-7836.2007.02656.x
  26. Price MJ, Endemann S, Gollapudi RR, et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 2008;29:992-1000. https://doi.org/10.1093/eurheartj/ehn046
  27. von Beckerath N, Kastrati A, Wieczorek A, et al. A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days. Eur Heart J 2007;28:1814-1819. https://doi.org/10.1093/eurheartj/ehl489
  28. Angiolillo DJ, Shoemaker SB, Desai B, et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation 2007;115:708-716. https://doi.org/10.1161/CIRCULATIONAHA.106.667741
  29. Jeong YH, Lee SW, Choi BR, et al. Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high post-treatment platelet reactivity: results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) randomized study. J Am Coll Cardiol 2009;53:1101-1109. https://doi.org/10.1016/j.jacc.2008.12.025
  30. Desta Z, Zhao X, Shin JG, Flockhart DA. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 2002;41:913-958. https://doi.org/10.2165/00003088-200241120-00002

Cited by

  1. Comparison of On-Treatment Platelet Reactivity Between Triple Antiplatelet Therapy With Cilostazol and Standard Dual Antiplatelet Therapy in Patients Undergoing Coronary Interventions : A Meta-Analysi vol.18, pp.6, 2011, https://doi.org/10.1177/1074248413495971
  2. Dual Antiplatelet Therapy Clopidogrel with Low-dose Cilostazol Intensifies Platelet Inhibition in Patients with Ischemic Stroke vol.52, pp.10, 2013, https://doi.org/10.2169/internalmedicine.52.9550
  3. Comparing the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in type 2 diabetes mellitus patients after coronary stents implantation: a systematic review an vol.15, pp.None, 2015, https://doi.org/10.1186/s12872-015-0114-1
  4. A pharmacodynamic study of the optimal P2Y 12 inhibitor regimen for East Asian patients with acute coronary syndrome vol.30, pp.5, 2015, https://doi.org/10.3904/kjim.2015.30.5.620
  5. Platelet Function Testing for Cardiac Surgery Patients on Antiplatelet Therapy: The Extreme Variability of Point-Of-Care Tests vol.11, pp.2, 2011, https://doi.org/10.13005/bpj/1412
  6. Cangrelor or Clopidogrel in Patients with Type 2 Diabetes Mellitus Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials vol.10, pp.3, 2011, https://doi.org/10.1007/s13300-019-0593-7