Analysis on influencing factors of antiplatelet drug resistance in patients with acute coronary syndrome

doi:10.3969/j.issn.1006-7795.2021.05.016

Abstract

Abstract: Objective To analyze the influencing factors of antiplatelet drug clopidogrel resistance in patients with acute coronary syndrome, so as to help clinicians quickly identify patients who may be resistant to antiplatelet therapy. Methods This study included patients with acute coronary syndrome who received coronary intervention and on dual antiplatelet at Fuwai Hospital throughout 2013. According to the results of thromboelastography (the result recorded as ADP-induced platelet-fibrin clot strength, MAADP,) the selected patients were divided into resistance group (MA_ADP>47 mm) and non-resistance group (MA_ADP≤47 mm). Via clinical data, univariate and multivariate logistic regression analysis were used to screen out influencing factors independently related to clopidogrel treatment resistance. Results A total of 2 511 patients were enrolled in the study, among them 781(31.10%) patients had clopidogrel treatment resistance. After univariate and further multivariate logistic regression analysis, five clinical factors were screened to be independently associated with resistance to antiplatelet therapy, namely reduced renal function (OR=3.08, 95%CI:1.28-7.36); female (OR=2.86, 95%CI:2.26-3.61); diabetes mellitus (OR=1.61, 95%CI:1.33-1.95); elevated platelet count (OR=1.55, 95%CI:1.07-2.25) and proton pump inhibitor use (OR=1.25, 95%CI:1.02-1.54). Conclusion Reduced renal function, female, diabetes, elevated platelet count and the use of proton pump inhibitors are the independent influencing factors of antiplatelet drug clopidogrel resistance in patients with acute coronary syndrome, which need to be paid attention in the clinical treatment, thereby guiding individualized antiplatelet therapy.

Key words: antiplatelet drug resistance, acute coronary syndrome, influencing factors, thromboelastography

CLC Number:

R541.4

Yao Yi, Tang Xiaofang, Song Ying, Jiang Lin, Qiao Shubin, Yuan Jinqing. Analysis on influencing factors of antiplatelet drug resistance in patients with acute coronary syndrome[J]. Journal of Capital Medical University, 2021, 42(5): 799-803.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2021.05.016

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2021/V42/I5/799

References

[1] Montalescot G, Sabatine M S. Oral dual antiplatelet therapy: what have we learnt from recent trials [J]. Eur Heart J,2016,37(4):344-352.
[2] Palmerini T, Della Riva D, Benedetto U, et al. Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11473 patients[J]. Eur Heart J, 2017, 38(14): 1034-1043.
[3] Dobesh P P, Finks S W, Trujillo T C. Dual antiplatelet therapy for long-term secondary prevention of atherosclerotic cardiovascular events[J]. Clin Ther,2020,42(10):2084-2097.
[4] Reny J L, Fontana P, Hochholzer W, et al. Vascular risk levels affect thepredictive value of platelet reactivity for the occurrence of MACE in patientson clopidogrel. Systematic review and meta-analysis of individual patientdata[J]. Thromb Haemost 2016,115:844-855.
[5] Notarangelo X F M,Maglietta G, Bevilacqua P, et al. Pharmacogenomic approach to selecting antiplatelet therapy in patients with acute coronary syndromes: the PHARMCLO trial[J]. J Am Coll Cardiol,2018,71(17): 1869-1877.
[6] Sibbing D, Aradi D, Alexopoulos D, et al. Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y 12 Receptor Inhibitor Treatment in Percutaneous Coronary Intervention[J]. JACC Cardiovasc Interv, 2019,12(16):1521-1537.
[7] Tang F X, Han Y L, Zhang J H, et al. CYP2C19 genotyping combined with on-clopidogrel platelet reactivity in predicting major adverse cardiovascular events in Chinese patients with percutaneous coronary intervention[J]. Thromb Res, 2016,147:108-114.
[8] Tang N, Yin S Y, Sun Z Y, et al. The relationship between on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes in Chinese patients[J] .Scand J Clin Lab Invest, 2015, 75(3):223-229.
[9] Li S, Liu H B, Liu J F, et al. Improved predictive value of GRACE risk score combined with platelet reactivity for 1-year cardiovascular risk in patients with acute coronary syndrome who underwent coronary stent implantation[J]. Platelets,2016,27(7):650-657.
[10]Cavallari L H, Lee C R, Beitelshees A L, et al. Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention[J].JACC Cardiovasc Interv,2018,11(2): 181-191.
[11]Chen S X, Zhang Y, Wang L L, et al.Effects of Dual-Dose Clopidogrel, Clopidogrel Combined with Tongxinluo Capsule, and Ticagrelor on Patients with Coronary Heart Disease and CYP2C19*2 Gene Mutation After Percutaneous Coronary Interventions (PCI) [J]. Med Sci Monit, 2017,23:3824-3830.
[12]Sardella G, Calcagno S, Mancone M, et al. Pharmacodynamic effect of switching therapy in patients with high on-treatment platelet reactivity and genotype variation with high clopidogrel dose versus prasugrel The RESET GENE Trial[J]. Circ Cardiovasc Interv, 2012, 5(5): 698-704.
[13]Htun P, Fateh-Moghadam S, Bischofs C, et al. Low responsiveness to clopidogrel increases risk among CKD patients undergoing coronary intervention[J]. J Am Soc Nephrol, 2011, 22:627-633.
[14]Jain N, Li X, Adams-Huet B, et al. Differences in whole blood platelet aggregation at baseline and in response to aspirin and aspirin plus clopidogrel in patients with versus without chronic kidney disease[J]. Am J Cardiol,2016, 117:656-663.
[15]Capodanno D, Angiolillo D J. Impact of race and gender on antithrombotic therapy[J]. Thromb Haemost,2010,104:471-484.
[16]Jastrzebska M, Marcinowska Z, Oledzki S, et al. Variable gender-dependent platelet responses to combined antiplatelet therapy in patients with stable coronary-artery disease[J]. J Physiol Pharmacol, 2018, 69(4):595-605.
[17]Marcucci R, Cioni G, Giusti B, et al. Gender and anti-thrombotic therapy: from biology to clinical implications[J]. J Cardiovasc Transl Res, 2014, 7:72-81.
[18]Geisler T, Mueller K, Aichele S, et al. Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions[J]. Clin Res Cardiol, 2010,99:743-752.
[19]Kukula K, Klopotowski M, Was J, et al. Factors related to on-treatment platelet aggregation assessed by multiple electrode aggregometry in percutaneous coronary intervention patients on clopidogrel and aspirin[J]. Postepy Kardiol Interwencyjnej, 2017, 13(3):210-217.
[20]谭知零.冠心病PCI患者服用双联抗血小板药物后氯吡格雷抵抗的发生情况及危险因素分析[J].解放军医药杂志,2018,30(6):75-78.
[21]Jakl M, Sevcik R, Ceral J, et al. Mean platelet volume and platelet count: overlooked markers of high on-treatment platelet reactivity and worse outcome in patients with acute coronary syndrome[J]. Anadolu Kardiyol Derg, 2014,14:85-86.
[22]Harvey A, Modak A, Dery U, et al. Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity[J]. J Breath Res, 2016, 10:017104.
[23]Weisz G, Smilowitz N R, Kirtane A J, et al. Proton pump inhibitors, platelet reactivity, and cardiovascular outcomes after drug-eluting stents in clopidogrel-treated patients:The ADAPT-DES Study[J]. Circ Cardiovasc Interv, 2015,8(10):e001952.