Clopidogrel responsiveness in chronic kidney disease patients with acute coronary syndrome

Abstract

Objective: Cardiovascular diseases are the leading cause of death in patients with chronic kidney disease (CKD). There is conflicting evidence about effect of CKD on clopidogrel responsiveness. We aimed to evaluate the clopidogrel responsiveness in CKD patients with acute coronary syndrome (ACS). Methods: A total of 101 patients; 55 with moderate to severe CKD and 46 with normal renal function or mild CKD, hospitalized with ACS were included in our study. Multiplate test was used to determine clopidogrel responsiveness. Platelet aggregation results were presented as aggregation unit (AU)*min and values over 470 AU*min were accepted as clopidogrel low responders. Results: The 101 patients (mean age 64.76±8.67 years; 61 [60.4%] male) were grouped into the two study groups as follows: group 1; 55 patients with eGFR60 ml/min/1.73 m2. 35 patients (34.7%) of the study population were found to have low response to clopidogrel (16 [34.8%] patients in group 1 and 18 [33.3%] patients in group 2, p=0.879) . There was no significant difference between group 1 and 2 for Multiplate test results (414.67±281.21 vs 421.56±316.19 AU*min, p=0.909). Clopidogrel low responsiveness were independently related to Multiplate test results of aspirin responsiveness (OR=1.004, CI 1.002–1.007, p=0.001) and hemoglobin (OR=0.727, CI 0.571–0.925, p=0.010). Multiplate results were also independently related to Multiplate test results of aspirin responsiveness (β=0.402, p60 ml/min/1.73 m2.

Keywords

• Acute coronary syndrome, chronic kidney disease, clopidogrel response

Clopidogrel responsiveness in chronic kidney disease patients with acute coronary syndrome

Abstract

Amaç: Kardiyovasküler hastalıklar, kronik böbrek hastalığı (KBH) olanlarda önde gelen ölüm sebebidir. KBH\' nın klopidogrel cevabı üzerine olan etkisi hakkında çelişkili kanıtlar vardır. Bu çalışmada, akut koroner sendromlu kronik böbrek hastalarında klopidogrel yanıtını değerlendirmeyi amaçladık. Yöntemler: Akut koroner sendrom ile hospitalize edilen; orta ileri KBH olan 55, normal böbrek fonksiyonu olan veya hafif KBH bulunan 46; toplamda 101 hasta çalışmaya dahil edildi. Klopidogrel yanıtını değerlendirmek için Multiplate testi kullanıldı. Trombosit agregasyon sonuçları agregasyon birimi (AU)*dak olarak verildi ve 470 AU*dak üzerindeki değerler klopidogrele düşük cevaplılar olarak kabul edildi. Bulgular: Çalışmaya dahil edilen 101 hasta (ortalama yaş 64.76±8.67, 61 [60.4%]\' i erkek) şu şekilde iki çalışma grubuna ayrıldı: grup 1; eGFH60 ml/dak/1.73 m2 olan 46 hasta. Çalışma populasyonundaki 35 hastada (34.7%) klopidogrele düşük yanıt bulundu (grup 1\'den 16 [34.8%] hasta; grup 2\'den 18 [33.3%] hasta, p=0.879). Multiplate test sonuçları açısından grup 1 ve 2 arasında anlamlı fark yoktu (414.67±281.21 vs 421.56±316.19 AU*dak, p=0.909). Klopidogrele düşük yanıt, aspirin cevabının Multiplate test sonuçları ile (odds ratio [OR]=1.004, confidence interval [CI] 1.002–1.007, p=0.001) ve hemoglobin ile (OR=0.727, CI 0.571–0.925, p=0.010) bağımsız olarak ilişkili idi. Yine Multiplate sonuçları; aspirin yanıtının Multiplate test sonuçları (β=0.402, p60 ml/dak/1.73 m2 olan hastalar arasında değişmiyor.

Keywords

• Akut koroner sendrom , kronik böbrek hastalığı, klopidogrel cevabı

References

1. Hamm CW, Bassand JP, Agewall S, et al. ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2011;32:2999-3054.
2. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Vari- ability in individual responsiveness to clopidogrel clinical implications, management, and future perspectives. J Am Coll Cardiol 2007;49:1505–1516.
3. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resis- tance is associated with increased risk of recurrent athero- thrombotic events in patients with acute myocardial infarc- tion. Circulation 2004;109:3171–3175.
4. Cuisset T, Frere C, Quilici J, et al. High post treatment plate- let reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome. J Thromb Hae- most 2006;4:542–549.
5. 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.
6. Abbott KC, Cruess DF, Agodoa LY, et al. Early renal in- sufficiency and late venous thromboembolism after renal transplantation in the United States. Am J Kidney Dis. 2004;43:120 –130.
7. Wattanakit K, Cushman M, Stehman-Breen C, et al. Chronic kidney disease increases risk for venous thromboembolism. J Am Soc Nephrol. 2008;19:135–140.
8. Mahmoodi BK, Gansevoort RT, Veeger NJ, et al. Preven- tion of Renal and Vascular End-stage Disease (PREVEND) Study Group. Microalbuminuria and risk of venous throm- boembolism. JAMA. 2009;301:1790 –1797.

9. Park SH, Kim W, Park CS, et al. A comparison of clopidogrel responsiveness in patients with versus without chronic re- nal failure. Am J Cardiol 2009;104:1292–1295.
10. Angiolillo DJ, Bernardo E, Capodanno D, et al. Impact of chronic kidney
11. disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet thera- py. J Am Coll Cardiol 2010;55:1139–1146.
12. Cuisset T, Frere C, Moro PJ, et al. Lack of effect of chronic kidney disease on clopidogrel response with high loading and maintenance doses of clopidogrel after acute coronary syndrome. Thromb Res. 2010;126:400-402.
13. Levey AS, Greene T, Schluchter MD, et al. Glomerular fil- tration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Con- trol and Complications Trial Research Group. J Am Soc Nephrol 1993;4:1159-1171.
14. Sibbing D, Braun S, Jawansky S, et al. Assessment of ADP- induced platelet aggregation with light transmission ag- gregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment. Thromb Haemost. 2008;99:121–126.
15. Weisser H, Von Pape K, Dzijan-Hom M, Calatzis A. Con- trol of aspirin effect in chronic cardiovascular patients using two whole blood platelet function assays: PFA-100 and Multiple electrode aggregometry. Clin Chem Lab Med 2006; 44:81-198
16. Best PJ, Steinhubl SR, Berger PB, et al. CREDO Inves- tigators. The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J 2008;155:687–693.
17. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Plate- let function profiles in patients with type 2 diabetes and cor- onary artery disease on combined aspirin and clopidogrel treatment. Diabetes 2005;54:2430–2435.
18. Soffer D, Moussa I, Harjai KJ, et al. Impact of angina class on inhibition of platelet aggregation following clopidogrel loading in patients undergoing coronary intervention: do we need more aggressive dosing regimens in unstable an- gina? Catheter Cardiovasc Interv 2003;59:21–25.
19. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Platelet aggregation according to body mass index in patients under- going coronary stenting: should clopidogrel loading-dose be weight adjusted? J Invasive Cardiol 2004;16:169 -174.
20. Angiolillo DJ, Bernardo E, Ramirez 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.
21. Taubert D, Kastrati A, Harlfinger S, et al. Pharmacokinetics of clopidogrel after administration of a high loading dose. Thromb Haemost 2004;92:311– 316.
22. Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduc- es the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 2003;107:32–37.
23. Morel O, Ghannudi S, Jesel L, et al. Cardiovascular Mortal- ity in Chronic Kidney Disease Patients Undergoing Percuta- neous Coronary Intervention Is Mainly Related to Impaired P2Y12 Inhibition by Clopidogrel. JACC 2011;57:399-408.
24. Htun P, Fateh-Moghadam S, Bischofs C, et al. Low Re- sponsiveness to Clopidogrel Increases Risk among CKD Patients Undergoing Coronary Intervention. J Am Soc Nephrol 2011;22:627-633.