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《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊  
日本科学技术振兴机构数据库(JST)
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医药导报, 2017, 36(8): 940-941
doi: 10.3870/j.issn.1004-0781.2017.08.024
经皮冠状动脉介入术后阿司匹林与氯吡格雷不耐受抗血小板方案选择
叶小春1,, 张耕1,, 陈霄2

摘要:

目的 探讨经皮冠状动脉介入(PCI)术后常规阿司匹林与氯吡格雷不耐受抗血小板药物的调整。方法 临床药师通过查阅文献,分析患者变态反应原因,调整抗血小板药物使用方案。结果 患者皮疹应为阿司匹林导致,临床药师建议改用替格瑞洛抗血小板治疗,取得满意疗效。结论 临床药师参与临床医疗团队合作,优化了治疗方案。

关键词: 阿司匹林 ; 氯吡格雷 ; 替格瑞洛 ; 西洛他唑 ; 过敏 ; 抗血小板 ; 临床药师

经皮冠状动脉介入(percutaneous coronary intervention,PCI)术后重点是预防心肌梗死和猝死,减轻症状和缺血发作[1]。指南推荐PCI术后常规服用阿司匹林与二磷酸腺苷(ADP)受体拮抗药1年。本文介绍1例阿司匹林发生不良反应后的处置。

1 病例概况

患者,男,45岁。近半年间断出现胸闷胸痛,于2016年2月1日在武汉市第一医院行PCI术,植入支架一枚,术后服阿司匹林肠溶片100 mg,po,qd;氯吡格雷片75 mg,po,qd;瑞舒伐他汀钙片10 mg,po,qd;铝碳酸镁片0.5 g,po,tid;泮托拉唑肠溶片40 mg,po,qd。2016年2月8日,出现肌肉酸痛,考虑为瑞舒伐他汀钙片引起不良反应,自行停服瑞舒伐他汀。2016年2月10日,全身出现红色皮疹,有瘙痒感和疼痛感,主要位于臀部、髂部、包皮,并伴有右侧眼睑水肿,认为是抗血小板药物引起不良反应,自行停服阿司匹林肠溶片与氯吡格雷片。2016年2月11日到武汉市第一医院门诊就诊,门诊检查结果均正常,特别是肝功能、肌酸激酶均正常。医生建议停用阿司匹林,服用氯吡格雷片150 mg,当日用药后上腹部不适,皮疹有所好转。2016年2月12日以冠心病、急性皮疹、药物过敏住院。体温:36.6 ℃,脉搏:84次·min-1,呼吸:20次·min-1,血压:110/80 mmHg(1 mmHg=0.133 kPa)。既往肺结核病史30年,已经治愈,6年前血吸虫肝病,3年慢性胃炎病史。曾对青霉素、头孢菌素(具体不详)过敏。诊断为:①冠心病,不稳定型心绞痛,回旋支PCI术后;②药物性皮疹。

2016年2月12日,全身红色皮疹,瘙痒和疼痛,予维生素C 、葡萄糖酸钙、枸地氯雷他定片、氢化可的松琥珀酸钠、阿司匹林肠溶片与氯吡格雷片、铝碳酸镁片。2016年2月13日皮疹减退,考虑在家时服用氯吡格雷腹部不适,停用氯吡格雷,改用替格瑞洛片90 mg,po,bid。2016年2月14日诉肌酸肌痛,浑身酸痛,身上并无明显皮疹,急查肌酸激酶,自己停服阿司匹林,自觉酸痛症状好转,要求停用阿司匹林,无明显皮疹,肌酸激酶结果正常。临床药师考虑为精神紧张所致,建议服用阿司匹林预防支架内血栓,但患者坚持停用阿司匹林。2016年2月15日,身上皮疹完全消退,停用维生素C、葡萄糖酸钙及枸地氯雷他定片。2016年2月16日鼻腔出血,考虑为替格瑞洛引起,将替格瑞洛剂量调为45 mg,po,bid,加用阿司匹林,当日鼻腔出血停止。2016年2月18日诉肌酸肌痛,后背出现皮疹,考虑为阿司匹林引起不良反应,停用阿司匹林。2016年2月19日皮疹大部分消退,替格瑞洛调为60 mg,po,bid,临床药师建议联合用西洛他唑抗血小板,患者坚持不使用其他抗血小板药物。因上次住院服用美托洛尔出现不适,一直未服用美托洛尔,为了降低心血管事件,2016年2月21日,予琥珀酸美托洛尔缓释片治疗。2016年2月22日,未诉特殊不适。2016年2月23日,加用阿托伐他汀钙片控制斑块治疗,血压偏低不宜服用血管紧张素转换酶抑制药(ACEI)或血管紧张素受体抑制药(ARB)类药物,(具体治疗药物见表1)情况稳定出院。出院诊断:①冠心病,不稳定型心绞痛,回旋支PCI术后;②药物性皮疹;③前降支肌桥。患者出院后再次复查时,服用阿托伐他汀未出现不适,其他药物耐受性均较好。

表1 患者治疗过程药物使用情况
住院后用药 用法、用量 用药日期
阿司匹林肠溶片 100 mg,po,qd 2016年2月12日—13日
2016年2月16日—17日
氯吡格雷片 75 mg,po,qd 2016年2月12日
铝碳酸镁片 0.5 g,po,tid 2016年2月12日—23日
维生素C注射液 3 g,静脉滴注,qd 2016年2月12日—14日
葡萄糖酸钙注射液 20 mL,静脉滴注,qd 2016年2月12日—14日
氢化可的松琥珀酸钠注射液 150 mg,静脉滴注,qd 2016年2月12日
枸地氯雷他定片 8.8 mg,po,qd 2016年2月12日—14日
替格瑞洛片 90 mg,po,bid 2016年2月13日—15日
45 mg,po,bid 2016年2月16日—18日
60 mg,po,bid 2016年2月19日—23日
琥珀酸美托洛尔缓释片 47.5 mg,po,qd 2016年2月21日—23日
阿托伐他汀 20 mg,po,qn 2016年2月23日

表1 患者治疗过程药物使用情况

2 讨论

患者住院后,多次调整抗血小板方案。国内外指南均推荐PCI术后服用双抗降低支架内血栓风险,过早停用双联抗血小板治疗的患者,会增加其后续心脏不良事件的发生率,有研究对比坚持1年双抗和过早停药的患者在死亡、再次血运重建、自发性心梗、支架内血栓形成、大出血和心脏不良事件发生率方面存在显著差异,前者优于后者[2]

目前抗血小板药物主要是环氧合酶(COX)抑制药与ADP受体拮抗药,在冠心病二级预防中,PCI术后使用阿司匹林与氯吡格雷联合抗血小板1年后,单用一种抗血小板药物即可,且首选阿司匹林,如不耐受再使用氯吡格雷 [3-4]。双抗期间阿司匹林与氯吡格雷均不耐受应如何选药?处理方法:①使用其他ADP受体拮抗药,替格瑞洛和普拉格雷均是ADP受体拮抗药,抗血小板方面作用更强,对临床预后更有效的降低心梗、心血管死亡等风险,均是替换氯吡格雷治疗的很好选择[5]。②联合应用西洛他唑[6]。有试验证实西洛他唑与氯吡格雷联合抗血小板治疗可显著降低PCI后再狭窄率,且西洛他唑与阿司匹林或氯吡格雷联用可以降低心血管事件[7]。③进行阿司匹林脱敏治疗。④研究显示非ST段抬高型心肌梗死的患者在行 PCI 治疗时使用双联抗血小板联合血小板糖膜蛋白IIb/IIIa(GPIIb/IIIa )受体拮抗药,比单独使用双联抗血小板的患者有更低的心梗、死亡的风险,但是目前GPIIb/IIIa受体拮抗药没有口服制剂,所以不能作为长期替代治疗方案[8]。在治疗过程中,临床药师从不良反应原因、解决方案、患者用药教育及心理辅导展开工作。因为阿司匹林导致皮疹,氯吡格雷胃肠道不适,故建议替格瑞洛联合西洛他唑抗血小板[9]。因为替格瑞洛60 mg,1天2次与90 mg,1天2次抗血栓作用相似[10]。在患者服用90 mg,1天2次,出血的情况下,故建议改为60 mg,1天2次,并建议加用西洛他唑。该患者可能存在心理因素,惧怕使用药物,临床药师多次与其沟通冠心病二级预防的重要性,对其宣讲药物不良反应知识,让其明白不良反应大部分患者可以耐受,应权衡获益与风险。

抗血小板治疗是冠心病的基础治疗措施之一,阿司匹林一直是冠心病二级预防的基石,但是极少数患者不能耐受阿司匹林。故需要调整治疗方案。临床药师的参与,保证了药物治疗的疗效,减少了药物不良事件。

The authors have declared that no competing interests exist.

参考文献

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The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial studied 202doses of ticagrelor, 90 mg twice a day (bid) and 60 mg bid, for long-term prevention of ischemic events in patients with prior myocardial infarction. Both doses similarly reduced the rate of ischemic events versus placebo. The pharmacokinetics and pharmacodynamics of ticagrelor 60 mg bid have not been studied. In this study, the authors sought to study the pharmacokinetics and pharmacodynamics for ticagrelor 60 mg compared with 90 mg bid. A total of 180 patients who received >4 weeks of study medication had blood sampling in the morning pre-maintenance dose and again 2 h post-dose. All patients received aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were determined. P2Y12inhibition was assessed by the VerifyNow P2Y12 assay (Accumetrics, Inc., San Diego, California) (P2Y12reaction units [PRU]), light transmittance aggregometry (adenosine diphosphate 5 and 20 μmol/l and arachidonic acid), and vasodilator-stimulated phosphoprotein phosphorylation assays. VerifyNow Aspirin assays and serum thromboxane B2measurements were performed. Mean pre- and post-dose plasma levels of ticagrelor were 35% and 38% lower, respectively, with 60 mg versus 90 mg. Both doses achieved high levels of platelet inhibition pre- and post-dose, with numerically slightly more variability with 60 mg: mean (SD) pre-dose PRU values were 59 ± 63 and 47 ± 43 for ticagrelor 60 and 90 mg, respectively (p02= 0.34). High platelet reactivity, determined as PRU >208, was rare with the 60-mg pre-dose and was absent post-dose. Platelet reactivity pre- and post-dose, as measured by light transmittance aggregometry or vasodilator-stimulated phosphoprotein assays, was numerically but not significantly lower with 90 mg than with 60 mg. Aspirin response was not affected by either dose. Ticagrelor 60 mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, similar to that with 90 mg bid, helping to explain the efficacy of the lower ticagrelor dose in PEGASUS-TIMI0254.
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关键词(key words)
阿司匹林
氯吡格雷
替格瑞洛
西洛他唑
过敏
抗血小板
临床药师


作者
叶小春
张耕
陈霄