CYP2C19基因型检测指导抗血小板治疗缺血性脑卒中的疗效及对预后的影响

Effect of CYP2C19 genotype detection in guiding antiplatelet therapy for ischemic stroke and its impact on prognosis

  • 摘要:
    目的 观察CYP2C19基因型检测指导抗血小板治疗对缺血性脑卒中(IS)患者的临床疗效及对心脑血管不良事件(MACCE)的影响。
    方法 选取130例IS患者,采用随机数字表法分为对照组(n=65)和观察组(n=65)。对照组患者接受阿司匹林和氯吡格雷方案治疗,观察组患者首先行CYP2C19基因型检测,根据CYP2C19基因型检测结果将观察组患者分为快代谢(CYP2C19*1/*1)组(n=30)、中代谢(CYP2C19*1/*2CYP2C19*1/*3)组(n=20)、慢代谢(CYP2C19*2/*2CYP2C19*3/*3CYP2C19*2/*3)组(n=15)。快代谢组患者接受氯吡格雷治疗,中代谢组患者仍采用氯吡格雷治疗,慢代谢组治疗首日采用阿司匹林治疗。所有患者随访1年。根据是否发生MACCE,将患者分为MACCE(n=28)和非MACCE组(n=102)。比较对照组和观察组血小板聚集情况、改良RANKIN量表(mRS)评分和MACCE发生率。采用单因素分析探讨MACCE组和非MACCE组临床资料的差异,采用多因素Logistic回归分析探讨IS患者预后MACCE发生的独立危险因素。
    结果 治疗1个月后,对照组、观察组的血小板聚集率均低于治疗前,快代谢组和中代谢组患者血小板聚集率低于对照组,血小板抑制率均高于对照组,差异有统计学意义(P < 0.05);慢代谢组和对照组治疗1个月后血小板抑制率、血小板聚集率差异均无统计学意义(P>0.05)。治疗1个月后,2组mRS评分均降低,且观察组低于对照组,差异有统计学意义(P < 0.05)。观察组MACCE发生率低于对照组,差异有统计学意义(P < 0.05);快代谢组和中代谢组MACCE发生率低于对照组,且中代谢组MACCE发生率最低,差异有统计学意义(P < 0.05)。Logistic回归模型结果发现,年龄大、高血压、糖尿病和左心室射血分数(LVEF) < 50%是IS患者MACCE发生的独立危险因素(P < 0.05)。
    结论 IS患者行CYP2C19基因型检测并给予不同分型患者相应治疗,可有效改善血小板聚集率和抑制率,降低MACEE的发生率,尤其对于CYP2C19*1/*2CYP2C19*1/*3基因型的中代谢患者而言,受益最大。IS患者MACEE发生的独立危险因素包括年龄大、高血压、糖尿病和LVEF < 50%,临床应对该类患者的病情密切监测,以改善预后。

     

    Abstract:
    Objective To observe the clinical efficacy of CYP2C19 genotype detection guided antiplatelet therapy in patients with ischemic stroke (IS) and its effect on adverse cardiovascular and cerebrovascular events (MACCE).
    Methods A total of 130 IS patients were selected in this study, and were divided into control group (n=65) and observation group (n=65) by random number table method. Patients in the control group were given aspirin and clopidogrel regimen, those in the observation group were firstly tested for CYP2C19 genotypes, and were further divided into fast metabolism (CYP2C19*1/*1) group(n=30), medium metabolism (CYP2C19*1/*2, CYP2C19*1/*3) group(n=20) and slow metabolism (CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3) group(n=15)based on the test results. Patients in the fast metabolism group were treated with clopidogrel, those in the middle metabolism were still treated with clopidogrel, and those in the slow metabolism group were given aspirin treatment at the first day of treatment. All patients were followed up for 1 year. According to the occurrence of MACCE, the patients were divided into MACCE group(n=28) and non-MACCE group(n=102). Platelet aggregation was compared between the control group and the observation group. Modified RANKIN Scale (mRS) scores and the incidence of MACCE were compared between control group and observation group. Univariate analysis was used to explore difference of clinical data between MACCE group and non-MACCE group; independent risk factors for the prognosis of MACCE in patients with IS were analyzed by multiple Logistic regression analysis.
    Results After 1 month of treatment, the platelet aggregation rates in the control group and observation group were lower than before treatment, the platelet aggregation rates in the fast metabolism group and middle metabolism group were lower than that in the control group, and the platelet inhibition rates in fast metabolism group and middle metabolism group were higher than that in control group (P < 0.05). There was no significant difference between the slow metabolism group and the control group in platelet aggregation rate and platelet inhibition rate (P>0.05). After 1 month of treatment, the mRS scores of both groups were significantly decreased, and the observation group was lower than the control group (P < 0.05). The incidence of MACCE in the observation group was significantly lower than that in control group (P < 0.05). The incidence rates of MACCE in the fast metabolism group and middle metabolism group were lower than those in the control group, and the incidence of MACCE in the middle metabolism group was the lowest(P < 0.05). Logistic regression model showed that older age, hypertension, diabetes and left ventricular ejection fraction(LVEF) < 50% were independent risk factors for MACCE in IS patients (P < 0.05).
    Conclusion For patients with IS, CYP2C19 genotype detection and corresponding treatment for patients with different subtypes can effectively improve their platelet aggregation rate and inhibition rate, and reduce the occurrence of MACEE, especially for patients with CYP2C19*1/*2 and CYP2C19*1/*3 types of medium metabolism who have the highest benefits. Independent risk factors for MACEE in patients with IS include older age, hypertension, diabetes and LVEF < 50%. Close clinical monitoring should be conducted to improve the prognosis of these patients.

     

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