CYP2 C19?2和CYP2 C19?17基因多态性与冠状动脉介入 治疗后病人氯吡格雷反应性的关联分析

目的 探究CYP2C19*2和CYP2C19*17基因多态性与冠状动脉介入治疗后病人氯吡格雷反应性的关系。方法 青海省心脑血管病专科医院于2014年3月至2017年3月期间招募了347例经皮冠状动脉介入的支架植入病人。采集经氯吡格雷(75 mg/d)治疗至少7 d的病人血液样品,用VerifyNow P2Y₁₂测定法测量血小板活性(PRU)和(%)抑制性。应用聚合酶链式反应检测CYP2C19*2(rs4244285)和CYP2C19*17(rs12248560)基因多态性,比较氯吡格雷应答组和无应答组病人CYP2C19*2(rs4244285)和CYP2C19*17(rs12248560)基因型的分布频率差异以及等位基因频率差异。结果 分组时,PRU>208的病人对氯吡格雷治疗无反应;104例(30%)病人为无应答者,243例(70%)病人为应答者。243例氯吡格雷应答组和104例无应答组CYP2C19*2(rs4244285)基因型分布频率野生型GG为80.7%/54.8%,杂合型GA为17.3%/38.5%,突变型AA为2.1%/6.7%,两组比较χ²=7.04,P<0.001;等位基因频率野生型G为89.3%/74.0%,突变型A为10.7%/26.0%,两组比较χ²=5.25,P<0.001。CYP2C19*17(rs12248560)基因型分布频率野生型CC为67.9%/75.0%,杂合型CT为30.5%/23.1%,突变型TT为1.6%/1.9%,两组比较χ²=0.81,P=0.388;等位基因频率野生型C为83.1%/84.1%,突变型T为16.9%/13.1%,两组比较χ²=0.68,P=0.416。结论 CYP2C19*2多态性与氯吡格雷治疗无反应相关,CYP2C19*17多态性增强了氯吡格雷的抗血小板活性。根据这两种多态性的单倍型,氯吡格雷治疗的病人可以被保护或不受支架血栓形成和缺血事件的威胁。     

The clinical effects of CYP2C19 *2 allele frequency on Palestinian patients receiving clopidogrel after percutaneous coronary intervention

BackgroundCYP2C19 loss-of-function polymorphic alleles (*2 and *3) have been documented to impair clopidogrel metabolism, and represent a risk factor for major adverse cardiac events. CYP2C19 polymorphism exhibits marked ethnic heterogeneity. Objective To determine the prevalence of CYP2C19 *2 and *3 alleles in a cohort of Palestinian patients managed with percutaneous coronary intervention and dual antiplatelet therapy, and to determine their role in causing major adverse cardiac events. Setting The blood samples were collected at the European Gaza Hospital, and the molecular techniques performed at the molecular genetics laboratory of the Islamic university of Gaza. Method The frequency of CYP2C19 *2 and *3 alleles was determined in 110 patients managed with percutaneous coronary intervention and clopidogrel. Genotyping was performed by PCR–RFLP. Personal and clinical data was obtained from patient record and 6-month follow-up for major adverse cardiac events. Main outcome measureCYP2C19 genotype, personal and clinical data and incidence of major adverse cardiac events. Results The frequency of CYP2C19 *1, *2 and *3 alleles was 82.3%, 15.5% and 2.3% respectively. Genotyping analysis showed that, 67.3% were homozygotes for CYP2C19 *1, 27.3% were *1/*2, 2.7% with *1/*3 genotype, 1.8% were *2/*3 and 0.9% were *2/*2. These frequencies were consistent with those of Caucasian populations. According to this study the poor metabolizers phenotype frequency was 2.7%, which is in the same range reported in Caucasians (2–5%) and lower than Oriental populations 13–23%. A strong significant relation was found between major adverse cardiac events and carrying the variant allele CYP2C19 *2 (P?=?0.001). On the other hand, there was no significant relation between major adverse cardiac events and carrying the variant allele CYP2C19 *3 (P?=?0.324). Conclusion The CYP2C19 *2 allele is relatively common in our population, and its associated reduced metabolic activity deserves attention as it leads to an increased incidence of major adverse cardiac events in the follow-up of patients receiving clopidogrel.

     

CYP2C19基因型功能缺失患者介入术后抗血小板治疗

目的：评价CYP2C19基因型功能缺失患者介入术后不同抗血小板治疗方案的安全性及有效性。方法：纳入择期冠脉支架植入术后行CYP2C19基因型检测的患者,按其表型分为快代谢组,中代谢组及慢代谢组,将中代谢组随机分为氯吡格雷双倍剂量组和氯吡格雷常规剂量联用西洛他唑组,慢代谢组随机分为替格瑞洛组和氯吡格雷常规剂量联用西洛他唑组,另设快代谢氯吡格雷常规剂量组为对照组,连续用药6个月,随访其临床事件。结果：所有患者中CYP2C19基因快、中、慢代谢型的比例分别为25%,60%, 15%;中代谢型患者使用氯吡格雷双倍剂量方案或氯吡格雷常规剂量联用西洛他唑方案、慢代谢患者使用替格瑞洛方案,可取得与快代谢型患者常规剂量氯吡格雷方案相似的疗效,但慢代谢患者使用氯吡格雷常规剂量联用西洛他唑预防心脏缺血的获益不佳,劣于替格瑞洛方案。结论：择期冠脉支架植入术后的中代谢患者在服用阿司匹林的基础上,采用氯吡格雷双倍剂量或氯吡格雷常规剂量联用西洛他唑的方案可能有益;慢代谢型患者建议使用替格瑞洛。     

瑞舒伐他汀和阿托伐他汀对不同基因型急性冠状动脉综合征患者氯吡格雷抗血小板活性的影响

目的观察瑞舒伐他汀和阿托伐他汀对不同基因型急性冠状动脉综合征患者氯吡格雷抗血小板活性的影响。方法选择200例急性冠状动脉综合征患者接受阿司匹林100 mg/d、氯吡格雷75 mg/d及低分子肝素5 000 U/12 h治疗,5 d后随机分为阿托伐他汀+正常基因组50例,阿托伐他汀+基因突变组50例,瑞舒伐他汀组+正常基因组50例,瑞舒伐他汀组+基因突变组50例。在服用氯吡格雷之前(基线值)、加用他汀类药物之前及服用他汀类药物7 d后,用全血阻抗法分别测定二磷酸腺苷(ADP)(10 mmol/L)诱导的血小板聚集率(PA)。结果 4组基线值无差别,与基线值比较,服用氯吡格雷5 d后和加服他汀类药物治疗7 d后,4组患者PA明显降低,差异有统计学意义(P<0.05);2组分别在不同基因组间的PA差异有统计学意义(P<0.05),不同他汀对同一基因组的PA差异无统计学意义(P>0.05)。结论经细胞色素3A4途径代谢的阿托伐他汀及不经细胞色素3A4代谢的瑞舒伐他汀,对同一基因组的PA活性无影响,对不同基因组患者氯吡格雷抗血小板活性有影响。     

CYP2C19基因多态性和风险评分与经皮冠状动脉介入术后预后的关系

目的 对CYP2C 19的基因多态性与风险评分对冠状动脉介入术（PCI）预后的关系进行分析探讨.方法 从2012年3月至2012年7月接收的行PCI患者中随机抽选40例,入院之前统一抽血检查CYP2C19基因,将患者按CYP2C19基因型分为三组：慢代谢型患者,中代谢型患者,和快代谢型患者.结果 经过检测,PRI VASP≥50％的患者为6例,PRI VASP＜50％的患者为34例,两组间PRI VASP比为（55.97±2.98）比（44.01±4.16）,两组比较差异有统计学意义（P＜0.05）.通过多元回归分析对导致PCI术后不良终点事件的因素进行分析得出：老龄、CYP2C19慢性代谢、2型糖尿病、左室射血分值、肾功能不全等5项因素为高危险因素.结论 对于慢代谢者可以通过增加氯吡格雷药物剂量,并联合给服阿司匹林以预防心血管事件发作.     

The impact of CYP2C19 and CYP2D6 genotypes on metabolism of amitriptyline in Japanese psychiatric patients

We investigated the effect of the CYP2C19 and CYP2D6 genotypes on the metabolism of amitriptyline (AT) in Japanese psychiatric patients. Steady-state concentrations of AT and its metabolites (nortriptyline [NT], trans-10-hydroxy-nortriptyline [EHNT], cis-10-hydroxy-nortriptyline [ZHNT], trans-10-hydroxy-amitriptyline [EHAT], and cis-10-hydroxy-amitriptyline [ZHAT]) in 50 patients were determined by high-performance liquid chromatography. Significantly higher plasma concentrations of AT corrected for dose and body weight in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 were observed (no mutated alleles vs. two mutated alleles: 36.0 +/- 18.2 vs. 64.0 +/- 25.2 ng/mL/mg/kg, p = 0.025). A significantly higher AT/NT ratio was seen in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 (no mutated alleles vs. two mutated alleles: 1.27 +/- 0.59 vs. 3.40 +/- 1.02, p = 0.001). A trend for higher NT/EHNT ratio in the subjects with two mutated alleles of CYP2D6 than in those with no mutated alleles of CYP2D6 was observed (no mutated alleles vs. two mutated alleles: 0.73 +/- 0.39 vs. 1.31 +/- 0.81, p = 0.068). A trend for higher plasma concentrations of total hydroxylated metabolites of AT (EHAT + ZHAT) corrected for dose and body weight in the subjects with two mutated alleles of CYP2C19 than in those with no mutated alleles of CYP2C19 was found (no mutated alleles vs. two mutated alleles: 9.5 +/- 5.8 vs. 17.8 +/- 8.9, p = 0.051). Therefore, the genotype of CYP2C19 is one of the important determinants of the plasma concentrations of AT and the capacity to desmethylate AT. Mother compound AT is shunted via hydroxylation pathways from AT to EHAT and ZHAT in the subjects with homozygotes of mutated alleles of CYP2C19 in order to compensate for the decreased capacity to desmethylate AT.     

The impact of the CYP2D6 and CYP2C19 genotypes on venlafaxine pharmacokinetics in a Japanese population

Objective: The cytochrome P ₄₅₀ isozymes CYP2D6 and CYP2C19 exhibit genetic polymorphism in human, including a marked interethnic difference. As the functional status of the isozymes CYP2D6 and CYP2C19 have an impact on the pharmacokinetics of some antidepressants, we investigated whether the disposition of venlafaxine was affected by the CYP2D6 and CYP2C19 genotypes. Methods: Twenty-eight adult Japanese men in good health participated in this study. Genomic DNA was isolated from peripheral lymphocytes, and the CYP2D6 genotype was determined using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis and XbaI-RFLP analysis. Subjects were categorized into the following four groups: group 1 CYP2D6*10/*10; group 2 CYP2D6*1/*10 and *2/*10; group 3 CYP2D6*1/*1, *1/*2 and *2/*2; and group 4 the other genotypes. Two defective CYP2C19 alleles (CYP2C19*2 and CYP2C19*3) were identified by means of PCR-RFLP analysis. Venlafaxine was administered orally following an overnight fast. Plasma concentrations of venlafaxine and O-desmethylvenlafaxine were monitored using high-performance liquid chromatography up to 24 h. Results: The peak plasma concentration and values of area under the concentration–time curve up to 24 h for venlafaxine were 298% and 453% higher for group 1 than group 3, and 91% and 120% higher for group 2 than for group 3, respectively. The homozygote for two defective alleles of CYP2C19 showed a higher concentration of venlafaxine within group 1 and group 2. Conclusion: The CYP2D6*10 allele and two CYP2C19 defective alleles, common in an Asian population, are the most likely genetic factors to use in determining interindividual differences in the pharmacokinetics of venlafaxine, although the results with respect to CYP2C19 are preliminary because of the few subjects used. Received: 6 July 1999 / Accepted in revised form 11 January 2000     

Effect of the CYP2C19*2 and *3 genotypes, ABCB1 C3435T and PON1 Q192R alleles on the pharmacodynamics and adverse clinical events of clopidogrel in Chinese people after percutaneous coronary intervention

Purpose

Chinese people are more frequent carriers of cytochrome P450 2C19 (CYP2C19) loss-of-function alleles than Caucasians. The effect of the ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase 1 (PON1) variants on platelet reactivity and clinical outcomes of clopidogrel treatment has not yet been reported in Chinese patients after percutaneous coronary intervention. The aim of this study was to investigate the effect of the CYP2C19, ABCB1, and PON1 variants on clopidogrel pharmacodynamics and clinical outcomes in these patients.

Methods

Six hundred and seventy patients after percutaneous coronary intervention were enrolled in a single-center registry. The antiplatelet effect of clopidogrel was assessed by thromboelastography, and the CYP2C19, ABCB1, and PON1 genotypes were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months.

Results

The frequency of the CYP2C19 loss-of-function alleles was relatively high (57.3 %). The risk of a low response to clopidogrel and composite ischemic events increased with the number of CYP2C19 loss-of-function alleles. However, there were not significant differences in clopidogrel pharmacodynamics and clinical outcomes across the ABCB1 and PON1 genotype groups; bleeding was not significantly different across the CYP2C19, ABCB1, and PON1 genotype groups.

Conclusions

The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients.     

Effect of glycyrrhizin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes

1. The objective of this study was to investigate the interaction between glycyrrhizin and omeprazole and observe the effects of glycyrrhizin on CYP2C19 and CYP3A4 activities in healthy Chinese male volunteers with different CYP2C19 genotypes.

2. Eighteen healthy subjects (six CYP2C19*1/*1, five CYP2C19*1/*2, one CYP2C19*1/*3, five CYP2C19*2/*2 and one CYP2C19*2/*3) were enrolled in a two-phase randomized crossover trial. In each phase, all subjects received placebo or glycyrrhizin salt tablet 150?mg twice daily for 14 consecutive days. The pharmacokinetics of omeprazole (20?mg orally on day 15) was determined for up to 12?h following administration by high-performance liquid chromatography.

3. After 14-day treatment of glycyrrhizin, plasma omeprazole significantly decreased, and those of omeprazole sulfone significantly increased. However, plasma concenetrations of 5-hydroxyomeprazole did not significantly change. The ratio of AUC_0–∞ of omeprazole to omeprazole sulfone decreased by 43.93% ± 13.56% (p?=?0.009) in CYP2C19*1/*1, 44.85% ± 14.84% (p?=?0.002) in CYP2C19*1/*2 or *3 and 36.16% ± 7.52% (p?<?0.001) in CYP2C19*2/*2 or *3 while those of omeprazole to 5-hydroxyomeprazole did not change significantly in all three genotypes. No significant differences in glycyrrhizin response were found among CYP2C19 genotypes.

4. Glycyrrhizin induces CYP3A4-catalyzed sulfoxidation of omeprazole and leads to decreased omeprazole plasma concentrations, but has no significant impact on CYP2C19-dependent hydroxylation of omeprazole.

     

CYP2C9和CYP2C19基因多态性对健康中国人口服氯吡格雷后药效动力学的影响

目的:研究细胞色素代谢酶CYP2C9和CYP2C19基因多态性对中国健康人口服氯吡格雷后药效动力学的影响。方法:24例健康男性受试者单剂量空腹口服氯吡格雷150 mg。用TaqMan探针方法进行CYP2C9和CYP2C19基因分型。测定药前和药后2,5,10,24和48 h血小板聚集率。结果:24例健康受试者空腹口服氯吡格雷150 mg后2 h即观察到血小板聚集率的下降,药效持续至药后48 h。Emax[MPA相对于基线的降低的百分比(IPA)的最大值]在CYP2C19*1/*1,*1/*2(or*3),*2/*3(or*2)携带者中分别为(60.3±21.0),(48.3±13.4)和(29.9±13.8),有显著性差异(P<0.05)。Emax在CYP2C9*1/*1,*1/*2(or*3)携带者中分别为(44.9±52.2)和(50.8±29.4),没有显著性差异。AUEC(IPA-时间曲线下面积)在CYP2C19*1/*1,*1/*2(or*3),*2/*3(or*2)携带者中分别为(22.8±9.8),(20.0±6.6)和(9.51±9.7),在CYP2C9*1/*1,*1/*2(or*3)携带者...     

Influences of different proton pump inhibitors on the anti-platelet function of clopidogrel in relation to CYP2C19 genotypes

AIMS

The efficacy of clopidogrel is influenced by CYP2C19 genotypes and substrates of CYP2C19, such as proton pump inhibitors (PPIs). We assessed the influence of three different PPIs on the anti-platelet function of clopidogrel in relation to CYP2C19 genotype status.

METHODS

Thirty-nine healthy volunteers with different CYP2C19 genotypes took clopidogrel 75 mg with or without omeprazole 20 mg, lansoprazole 30 mg or rabeprazole 20 mg in the morning for 7 days. The influence of the three PPIs on the anti-platelet function of clopidogrel was determined. A less than 30% inhibition of platelet aggregation (IPA) during clopidogrel dosing was defined as a ‘low responder’. We also examined whether evening dosing of omeprazole could prevent the interaction with clopidogrel dosed in the morning.

RESULTS

In rapid metabolizers (RMs, *1/*1, n = 15) of CYP2C19, omeprazole and rabeprazole significantly attenuated the anti-platelet function of clopidogrel. In decreased metabolizers (DMs, carriers of *2 and/or *3, n = 24), there was a large variation in IPA and there was a trend but no significant decrease in IPA when placed on a concomitant PPI. Some DMs became ‘low-responders’ when placed on a concomitant PPI. Evening omeprazole dose in RMs did not seem to cause a significant decrease in IPA in contrast to morning dosing, but did so in DMs.

CONCLUSIONS

The three PPIs affected the efficacy of clopidogrel to different degrees. Both omeprazole and rabeprazole significantly decreased IPA in RMs but not DMs, although there was a trend towards lower IPA in DMs. Morning and evening dosing of omeprazole were both associated with lower IPA in DMs.     

CYP2D6 and CYP2C19 genotypes in an elderly Swedish population

Objective: Eighty-three healthy elderly Swedish subjects (age 87 ± 4 years, mean ± SD, range 80–98 years) were genotyped with respect to the two genetic polymorphisms of oxidative drug metabolism, CYP2D6 and CYP2C19, using allele-specific polymerase chain reaction (PCR). A control population consisted of 248 younger unrelated healthy volunteers (age 31 ± 9 years, range 19–63 years) for CYP2D6, and 162 (age 30 ± 8 years, range 19–55 years) for CYP2C19. Results: No significant differences were found between the control groups and the elderly subjects with respect to the frequencies of the defect alleles CYP2D6*3, CYP2D6*4, CYP2C19*2 and CYP2C19*3. Neither were there any differences in the genotype frequencies, or the predicted phenotype frequencies. The study indicates that the CYP2D6 and CYP2C19 genotypes play no major role in the probability of reaching high age. Conclusion: No genetically determined differences in the pharmacokinetics of drugs metabolized by these two polymorphic enzymes are to be expected in the oldest age groups compared with younger adults. Received: 10 March 1998 / Accepted: 1 May 1998     

血栓弹力图法和VerifyNow P2Y12法评估CYP2C19基因多态性对氯吡格雷反应性的影响

目的：通过血栓弹力图法（TEG）和VerifyNow P2Y12法检测来评估CYP2C19基因多态性对急性冠脉综合征（ACS）患者服用氯吡格雷疗效的影响，并比较2种方法检测结果的差异。方法：入选2017年10月至2018年10月因ACS入院且服用氯吡格雷（75 mg·d^-1）和阿司匹林（100 mg·d^-1）的患者230例，使用焦磷酸测序检测其CYP2C19基因型，并在服用氯吡格雷7 d后，使用TEG法检测其二磷酸腺苷（ADP）诱导的血小板聚集抑制率和VerifyNow P2Y12法检测其血小板反应单位（PRU）。结果：TEG法结果显示CYP2C19快代谢型、中间代谢型和慢代谢型患者出现氯吡格雷抵抗的比例分别为8.9%、40.2%和59.4%。VerifyNow P2Y12法检测结果显示各代谢型患者出现氯吡格雷抵抗的比例分别为6.9%、29.9%和50.0%。慢代谢型及中间代谢型患者出现氯吡格雷抵抗的概率明显高于快代谢组（P<0.05）。2种方法氯吡格雷抵抗检出率差异无显著性（P>0.05），检测结果显著相关（r=-0.719，P<0.001）。结论：CYP2C19基因多态性显著影响ACS患者服用氯吡格雷的疗效。TEG法和VerifyNow P2Y12法检测抗血小板聚集结果具有相关性。     

Efffect of the ABCC3 –211C/T polymorphism on clopidogrel responsiveness in patients with percutaneous coronary intervention

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Long-term clopidogrel therapy in patients receiving percutaneous coronary intervention

BACKGROUND: The PCI-CURE (Percutaneous Coronary Intervention-Clopidogrel in Unstable Angina to Prevent Recurrent Events) and CREDO (Clopidogrel for the Reduction of Events During Observation) studies have demonstrated that, in addition to aspirin, pre-treatment with clopidogrel followed by long-term (i.e. 9-12 months) therapy significantly reduces the risk of atherothrombotic events in patients undergoing percutaneous coronary intervention (PCI). OBJECTIVE: To examine the economic implications, from the Dutch healthcare perspective, of the use of clopidogrel in patients undergoing PCI (elective procedures or in patients with acute coronary syndrome), comparing pre-treatment followed by long-term therapy with only 4 weeks of treatment. METHODS: A lifetime Markov model was used to combine data from the PCI-CURE and CREDO trials with data from the literature concerning epidemiology, costs and quality of life. The model was run separately for each trial. Only direct healthcare costs (euro, year 2004 values) were considered. Costs and outcomes were discounted at 4% per anum. For each trial, the cost effectiveness is expressed as costs per life-year and QALY gained. Uncertainties are addressed by uni- and probabilistic multivariate sensitivity analysis. RESULTS: When starting with the data from the PCI-CURE trial, pre-treatment plus 9-month clopidogrel therapy was predicted to save 1119 euros and gain 0.03 life-years and 0.07 QALYs per patient compared with short-term treatment. When starting with the data from the CREDO trial, the combination of pre-treatment and prolonged clopidogrel therapy (1 year) was estimated to save 497 euros and gain 0.10 life-years and 0.14 QALYs per patient. Univariate and probabilistic multivariate sensitivity analyses suggested that the conclusions were generally robust, but that the expected gain in survival for the PCI-CURE population was very sensitive to the effects on mortality within the combined endpoint of myocardial infarction/stroke-free survival. CONCLUSIONS: In The Netherlands, pre-treatment plus long-term (9-12 months) therapy with clopidogrel is estimated to save costs and increase (quality-adjusted) survival in the prevention of ischaemic events among patients undergoing elective PCI (CREDO) and in patients with acute coronary syndrome (PCI-CURE) compared with short-term treatment with clopidogrel without pre-treatment.     

冠脉介入治疗围手术期使用氯吡格雷的循证医学证据

目的总结氯吡格雷在冠脉介入治疗（PCI）患者中应用的循证医学证据。方法检索Pubmed、Cochrane Library、CNKI、中文科技期刊数据库、万方数据库从建库至2014年2月的有关文献,根据纳入相关标准进行文献收集,然后对其作用机制、有效性系统评价文献汇总分析。结果共纳入33篇meta分析文献,证实氯吡格雷在PCI患者中抗血小板治疗的有效性,认为其高剂量维持和高剂量负荷并采取预治疗的策略似乎更有益。结论氯吡格雷是临床应用广泛的抗血小板药物,虽存在一定的局限,但其与阿司匹林联用,目前在PCI患者中发挥着积极的作用。     

CYP2C19基因多态性与冠心病氯吡格雷疗效的关系

观察CYP2C19基因多态性与新疆汉族人群中冠心病患者氯吡格雷常规剂量抗血小板治疗疗效的关系。选择诊断明确且进行了CYP2C19基因多态性检测的冠心病患者168例,其中包括经PCI术后组99例和经选择性冠状动脉造影术明确诊断多支病变不宜行PCI而又未接受CABG患者69例。根据CYP2C19基因型不同,PCI组又分为快代谢型49例和中慢代谢型50例;多支病变组分为快代谢型34例和中慢代谢型35例;均接受口服常规剂量氯吡格雷75 mg/d加阿司匹林100 mg/d行抗凝治疗1年。对比分析4组院外用药情况、不良心血管事件、出血事件的发生情况。（1）多支病变组β受体阻滞剂和尼可地尔的使用率高于PCI组;PCI组的中慢代谢型和多支病变组硝酸酯类使用率高于PCI组的快代谢型;多支病变组中慢代谢型ACEI/ARB的使用率高于PCI组中慢代谢型和多支病变组的快代谢型（均P＜0.05）。（2）多支病变组非致死性心肌梗死发生率高于PCI组（P＜0.05）;PCI组的中慢代谢型和多支病变组心绞痛的再发率高于PCI组的快代谢型（均P＜0.05）;而心源性死亡、支架内血栓形成、再次血运重建的发生率4组比较无显著性差异。（3）4组间出血事件发生率均无显著性差异。（4）多因素Logistic回归分析结果显示,CYP2C19*2的基因型、糖尿病病史、高血压病史是发生不良心血管事件的相关因素。CYP2C19基因多态性与PCI后及多支病变冠心病患者院外再发心绞痛、非致死性心肌梗死和口服药物种类有关,CYP2C19*2是不良心血管事件发生的高危因素之一,CYP2C19功能缺失基因的多态性影响抗凝治疗后冠心病患者的预后。