多重用药对冠心病患者发生氯吡格雷抵抗的影响研究

Influence of Polypharmacy on Clopidogrel Resistance in Patients with Coronary Heart Disease

背景多重用药是药物相互作用的主要危险因素,冠心病患者常面临多重用药的问题;冠心病二级预防基础药物氯吡格雷的活性极易受到药物相互作用的影响,但多重用药对于氯吡格雷疗效的影响尚未见报道。目的分析多重用药对冠心病患者发生氯吡格雷抵抗(CR)的相关影响因素。方法选取南京医科大学附属无锡市人民医院2015年9月-2018年3月符合纳入标准的冠心病患者333例,根据血小板聚集率(PAR)分为CR组(PAR>50%)132例与对照组(PAR≤50%)201例。通过医院信息系统收集基本资料,包括基本信息〔性别、年龄、吸烟、饮酒、合并疾病、心功能分级、是否行冠状动脉介入术治疗〕;体格检查及实验室检查〔体质指数(BMI)、血压、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)、血肌酐(Scr)、丙氨酸氨基转移酶(ALT)、PAR〕;用药情况〔质子泵抑制剂(PPI)、地尔硫、他汀类药物(阿托伐他汀及辛伐他汀)、钙通道拮抗剂(CCB)、血管紧张素受体拮抗剂(ARB)、美托洛尔、硝酸酯类、曲美他嗪、含抗栓成分中药注射剂、低分子肝素〕。采用多因素Logistic回归分析探讨冠心病患者发生CR的影响因素。结果 CR组患者高血压合并率、BMI≥25.0 kg/m^2发生率、LDL-C≥2.07mmol/L比例、FBG、多重用药(≥7种)比例高于对照组(P<0.05)。多因素Logistic回归分析结果显示,FBG(≥6.1mmol/L)(OR=1.121,P=0.033)、多重用药(≥7种)(OR=5.224,P=0.003)是CR的影响因素。CR组患者含抗栓成分中药注射剂、低分子肝素使用率高于对照组(P<0.05)。结论 FBG、多重用药(≥7种)是冠心病患者发生CR的影响因素,合并使用含抗栓成分中药注射剂、低分子肝素可能与冠心病患者发生CR有关,临床应予以重视。

Background Polypharmacy is a major factor that can lead to potentially dangerous drug interactions.Patients with coronary heart disease(CHD) often face problems of polypharmacy.Clopidogrel,a basic drug for secondary prevention of CHD,its antiaggregating activity is easily influenced by drug interactions.However,the influence of polypharmacy on the effect of clopidogrel has been rarely reported.Objective To analyze the factors associated with clopidogrel resistance(CR) in patients with CHD treated with polypharmacy.Methods According to the inclusion and exclusion criteria,333 cases of CHD were enrolled from Wuxi People’s Hospital,Nanjing Medical University,from September 2015 to March 2018.Through the information system of the hospital,basic information(including sex,age,prevalence of smoking,prevalence of drinking,comorbidity,clinical diagnosis,NYHA functional classification,PCI treatment),physical examination and laboratory results〔including body mass index(BMI),blood pressure,total cholesterol,low-density lipoprotein cholesterol(LDL-C),fasting blood glucose(FBG),serum creatinine,alanine aminotransferase and platelet aggregation rate(PAR)〕,and medication〔including proton pump inhibitors(PPI),diltiazem, statins(atorvastatin and simvastatin), calcium channel antagonists(CCB),ARB,metoprolol,nitrates,trimetazidine,traditional Chinese medicine containing anti-thrombotic ingredients,low molecular weight heparin〕 were collected.On the basis of the PAR level,132 cases were assigned to the CR group(PAR>50%),and 201 were assigned to the control group(PAR ≤ 50%),respectively.Factors associated with CR were identified by multivariate Logistic regression analyses.Results The incidence of hypertension,rates of BMI ≥25.0 kg/m^2,LDL-C ≥ 2.07 mmol/L,FBG,and polypharmacy(≥ 7)were significantly higher in CR group than those of the control group(P<0.05).Multivariate Logistic regression analysis showed that FBG(≥ 6.1 mmol/L)(OR=1.121,P=0.033) and concomitant medications(≥ 7)(OR=5.224,P=0.003) were associated factors for CR.The combined use rates of traditional Chinese medicine injection containing antithrombotic components and low molecular weight heparin were also obviously higher in the CR group(P<0.05).Conclusion FBG and polypharmacy(≥7) are associated with CR.Moreover,combined use of low molecular weight heparin and traditional Chinese medicine injections containing antithrombotic ingredients may also be related to CR.