Relationship between Clopidogrel Resistance and Major Adverse Cardiac Events in Elderly Patients with Acute Coronary Syndrome_West China Medical Journal

Authors：

 TAOTao , WANGShu-xia , WANGHao , GUOYu-tao , ZHUPing ,  WANGYu-tang

Cardiovascular Department 1, PLA General Hospital, Beijing 100853, P. R. China;

Corresponding author：

WANGYu-tang, Email: wangyt301@gmail.com

Keywords：

Acute coronary disease; Clopidogrel resistance; Major adverse cardiac events; Platelet aggregation; Elderly

DOI：

10.7507/1002-0179.20140443

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Objective To investigate the impact of clopidogrel resistance on the long-term prognosis in the elderly with acute coronary syndrome (ACS), as clopidogrel is widely used for secondary prevention in the patients with ACS, while studies on the relationship between clopidogrel resistance and long-term outcome in the elderly with ACS are limited. Methods Three hundred elderly patients with ACS, aged from 70 to 95, with on average age of (81.3±6.4) years old, receiving clopidogrel (75 mg, once a day) over one month between January 2009 and December 2010 were followed up for major adverse cardiac events (MACE, including cardiac death, non-fatal re-myocardial infarction, angina, ischemia stroke/TIA, acute thrombosis and hemorrhage). Platelet aggregation was measured by light transmission aggregometry using adenosine diphosphate as a stimulus. According to the variation of platelet aggregation, the patients were divided into clopidogrel resistance group (<10%) and non-lopidogrel resistance group (≥10%). The median follow-up was 2 years. A Cox hazard proportional model was used to estimate time to outcome associated with clopidogrel resistance and MACE. Results The incidence of clopidogrel resistance was 24.0% in our study population. Patients with diabetes, renal insufficiency, or a higher body mass index tended to have clopidogrel resistance. Compared with those patients without clopidogrel resistance, there was significantly increased MACE in patients with clopidogrel resistance (37.5%, 22.8%; P=0.032). Additionally, Cox hazard proportional model analysis demonstrated that clopidogrel resistance was an independently risk factor for MACE[HR=2.34, 95% CI (1.07, 4.57), P=0.016]. Conclusion Diabetes, renal insufficiency and high body max index are associated with clopidogrel resistance, which can predict the increased risk of MACE in elderly patients with ACS.

Citation： TAOTao, WANGShu-xia, WANGHao, GUOYu-tao, ZHUPing, WANGYu-tang. Relationship between Clopidogrel Resistance and Major Adverse Cardiac Events in Elderly Patients with Acute Coronary Syndrome. West China Medical Journal, 2014, 29(8): 1439-1442. doi: 10.7507/1002-0179.20140443 Copy

1.	Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation[J]. N Engl J Med, 2001, 345(7):494-502.
2.	Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention:a randomized controlled trial[J]. JAMA, 2002, 288(19):2411-2420.
3.	Coccheri S. Antiplatelet therapy:controversial aspects[J]. Thromb Res, 2012, 129(3):225-229.
4.	Snoep JD, Hovens MM, Eikenboom JC, et al. Clopidogrel nonresponsivenesa in patients undergoing percutsneous coronary intervention with atenting:a systematic review and mets-analysis[J]. Am Heart J, 2007, 154(2):221-231.
5.	Geisler T, Schaeffeler E, Dippon J, et al. CYP2C19 and nongenetic factors predict poor responsiveness to clopidogrel loading dose after coronary stent implantation[J]. Pharmacogenomics, 2008, 9(9):1251-1259.
6.	Ferreiro JL, Angiolillo DJ. Challenges and perspectives of antiplatelet therapy in patients with diabetes mellitus and coronary artery disease[J]. Curr Pharm Des, 2012,18(33):5273-5293.
7.	Mangiacapra F, Patti G, Peace A, et al. Comparison of platelet reactivity and periprocedural outcomes in patients with versus without diabetes mellitus and treated with clopidogrel and percutaneous coronary intervention[J]. Am J Cardiol, 2010, 106(5):619-623.
8.	Silva FB, Almeida Junior GL, Neno A, et al.Resistance to clopidogrel:prevalence and associate variables[J]. Arq Bras Cardiol, 2012, 99(6):1135-1141.
9.	李蕾, 韩江莉, 李海燕, 等. 抗血小板药物抵抗对急性心肌梗死患者再发心脏缺血事件的预价值[J]. 中华医学杂志, 2012, 92(38):2677-2680.
10.	Park J, Shin DH, Kim BK. et al. Relationship between aspirin/clopidogrel resistance and intra-stent thrombi assessed by follow-up optical coherence tomography after drug-eluting stent implantation[J]. Eur Heart J Cardiovasc Imaging, 2013, 14(12):1181-1186.
11.	Mobley JE, Bresee SJ, Wortham DC, et al. Frequency of nonresponse antiplatelet activity of clopidogrel during pretreatment for cardiac catheterization[J]. Am J Cardiol, 2004, 93(4):456-458.
12.	Al-Azzam SI, Alzoubi KH, Khabour OF, et al. Factors that contribute to clopidogrel resistance in cardiovascular disease patients:environmental and genetic approach[J]. Int J Clin Pharmacol Ther, 2013, 51(3):179-186.

1. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation[J]. N Engl J Med, 2001, 345(7):494-502.
2. Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention:a randomized controlled trial[J]. JAMA, 2002, 288(19):2411-2420.
3. Coccheri S. Antiplatelet therapy:controversial aspects[J]. Thromb Res, 2012, 129(3):225-229.
4. Snoep JD, Hovens MM, Eikenboom JC, et al. Clopidogrel nonresponsivenesa in patients undergoing percutsneous coronary intervention with atenting:a systematic review and mets-analysis[J]. Am Heart J, 2007, 154(2):221-231.
5. Geisler T, Schaeffeler E, Dippon J, et al. CYP2C19 and nongenetic factors predict poor responsiveness to clopidogrel loading dose after coronary stent implantation[J]. Pharmacogenomics, 2008, 9(9):1251-1259.
6. Ferreiro JL, Angiolillo DJ. Challenges and perspectives of antiplatelet therapy in patients with diabetes mellitus and coronary artery disease[J]. Curr Pharm Des, 2012,18(33):5273-5293.
7. Mangiacapra F, Patti G, Peace A, et al. Comparison of platelet reactivity and periprocedural outcomes in patients with versus without diabetes mellitus and treated with clopidogrel and percutaneous coronary intervention[J]. Am J Cardiol, 2010, 106(5):619-623.
8. Silva FB, Almeida Junior GL, Neno A, et al.Resistance to clopidogrel:prevalence and associate variables[J]. Arq Bras Cardiol, 2012, 99(6):1135-1141.
9. 李蕾, 韩江莉, 李海燕, 等. 抗血小板药物抵抗对急性心肌梗死患者再发心脏缺血事件的预价值[J]. 中华医学杂志, 2012, 92(38):2677-2680.
10. Park J, Shin DH, Kim BK. et al. Relationship between aspirin/clopidogrel resistance and intra-stent thrombi assessed by follow-up optical coherence tomography after drug-eluting stent implantation[J]. Eur Heart J Cardiovasc Imaging, 2013, 14(12):1181-1186.
11. Mobley JE, Bresee SJ, Wortham DC, et al. Frequency of nonresponse antiplatelet activity of clopidogrel during pretreatment for cardiac catheterization[J]. Am J Cardiol, 2004, 93(4):456-458.
12. Al-Azzam SI, Alzoubi KH, Khabour OF, et al. Factors that contribute to clopidogrel resistance in cardiovascular disease patients:environmental and genetic approach[J]. Int J Clin Pharmacol Ther, 2013, 51(3):179-186.

West China Medical Journal

Relationship between Clopidogrel Resistance and Major Adverse Cardiac Events in Elderly Patients with Acute Coronary Syndrome

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