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丹参酮ⅡA联合尼可地尔对冠心病左主干病变患者的临床疗效分析

2020-11-09胡立波刘翔

中国医学创新 2020年25期
关键词:尼可地尔丹参酮冠心病

胡立波 刘翔

【摘要】 目的:觀察丹参酮ⅡA联合尼可地尔对冠心病左主干病变患者的临床疗效。方法:选取2016年10月-2019年7月在湖南省脑科医院心内科住院治疗的冠心病患者60例为研究对象。通过随机数字表法将其分为试验组和对照组,每组30例。对照组予以尼可地尔治疗,试验组予以丹参酮ⅡA磺酸钠注射液联合尼可地尔治疗。治疗2周后比较两组胸痛症状改善情况、心电图总有效情况及超敏C反应蛋白(hs-CRP)水平,并比较治疗后3个月两组左室射血分数(LVEF)和6 min步行试验距离。结果:治疗2周后,两组胸痛发作频率、持续时间均治疗前有明显改善,且试验组发作频率低于对照组,持续时间短于对照组,差异均有统计学意义(P<0.05)。治疗后,试验组心电图总有效率为86.67%,高于对照组的63.33%,差异有统计学意义(P<0.05)。治疗后,两组hs-CRP水平均较治疗前下降,且试验组hs-CRP水平低于对照组,差异均有统计学意义(P<0.05)。治疗后3个月,两组LVEF、6 min步行试验距离均较治疗前明显改善,且试验组LVEF较对照组改善更显著,差异均有统计学意义(P<0.05)。结论:对左主干病变的冠心病患者采用丹参酮ⅡA磺酸钠注射液联合尼可地尔治疗,可有效缓解症状,进一步提高临床效果,显著改善患者心脏功能的远期预后。

【关键词】 冠心病 左主干病变 丹参酮 尼可地尔

Clinical Efficacy Analysis of Tanshinone ⅡA Combined with Nicorandil in Patients with Left Main Coronary Artery Disease/HU Libo, LIU Xiang. //Medical Innovation of China, 2020, 17(25): 00-005

[Abstract] Objective: To observe the clinical efficacy of Tanshinone ⅡA combined with Nicorandil in the treatment of left main coronary artery disease. Method: A total 60 patients with coronary heart disease who were hospitalized in the Department of Cardiology of Hunan Brain Hospital from October 2016 to July 2019 were selected as the research objects. They were divided into experimental group and control group by random number table method, 30 cases in each group. The control group was treated with Nicorandil, the experimental group was treated with Tanshinone ⅡA Sodium Sulfonate Injection combined with Nicorandil. After 2 weeks of treatment, the improvement of chest pain symptoms, the total effective rate of electrocardiogram and the level of high sensitive C-reactive protein (hs-CRP) were compared between the two groups. The left ventricular ejection fraction (LVEF) and the 6-minute walking test distance were compared between the two groups 3 months after treatment. Result: After 2 weeks of treatment, the frequency and duration of chest pain in the two groups were significantly improved before treatment, the attack frequency of the experimental group was lower than that of the control group, and the duration was shorter than that of the control group, the differences were statistically significant (P<0.05). After treatment, the total effective rate of ECG in the experimental group was 86.67%, which was higher than 63.33% in the control group, the difference was statistically significant (P<0.05). After treatment, the level of hs-CRP in the two groups decreased compared with those of before treatment, and the level of hs-CRP in the experimental group was lower than that in the control group, the differences were statistically significant (P<0.05).

3 months after treatment, LVEF and 6-min walking distance of the two groups were significantly improved compared with those of before treatment, and the LVEF of the experimental group was more significantly improved than that of the control group, the differences were statistically significant (P<0.05). Conclusion: Tanshinone ⅡA Sodium Sulfonate Injection combined with Nicorandil can effectively relieve symptoms, further improve clinical effect, and significantly improve the long-term prognosis of patients with left main coronary artery disease.

[Key words] Coronary heart disease Left main coronary artery disease Tanshinone Nicorandil

First-authors address: Hunan University of Chinese Medicine, Changsha 410208, China

doi:10.3969/j.issn.1674-4985.2020.25.001

冠状动脉左主干病变(left main coronary artery disease, LMCA)是指冠脉造影显示左主干狭窄≥50%,占冠心病患者的4%~6%,因其高危险、高死亡率,一直受到心内科医师的高度重视,且在不断地积极探求LMCA的有效治疗策略[1-2]。既往CABG被列为UPLM的标准治疗,近年来随着对左主干病变解剖特征研究的深入、介入治疗器械的发展(DES的广泛应用)及介入技术的成熟,最新指南将不适合行CABG治疗的冠心病患者行PCI治疗列为Ⅱb类适应证[3]。然而由于患者冠脉血管条件或患者家庭经济等其他原因,部分患者拒绝或无法行PCI或CABG治疗,因此使用药物保守治疗改善左主干病变患者的临床症状及生活质量就显得尤为重要。丹参酮ⅡA是中药丹参根茎中分离得到的一种药理活性成分,能够防止动脉粥样硬化、心肌损伤和心肌肥厚。丹参酮ⅡA被发现还有抑制炎症因子的表达及生成从而减轻炎症反应[4-6];尼可地尔是一种非选择性三磷酸腺苷(ATP)敏感钾离子(K+)通道开放剂,临床研究发现尼可地尔使血管平滑肌放松,有效扩张微血管,改善心肌灌注[7-8]。最近的基础和临床研究显示了其对心肌损伤的保护作用,减少了心血管事件发生风险[9-10]。本文旨在探讨丹参酮ⅡA磺胺钠注射液联合尼可地尔治疗左主干病变患者的临床疗效。现报道如下。

1 资料与方法

1.1 一般资料 选取2016年10月-2019年7月在湖南省脑科医院心内科住院治疗的冠心病患者60例为研究对象。(1)纳入标准:近1年行冠脉造影确诊冠状动脉左主干狭窄≥50%,未能或拒绝行PCI或CABG血运重建治疗,要求药物保守治疗。(2)排除标准:严重心力衰竭(射血分数<30%),严重心律失常,合并严重肝、肾疾病,类风湿关节炎或其他自身免疫性疾病,感染,恶性肿瘤,血液系统疾病及病史,未取得知情同意者。通过随机数字表法分为试验组和对照组,每组30例。本研究符合医学伦理学标准,均已取得患者及家属同意,研究经医院医学伦理委员会批准。

1.2 方法 两组均予以冠心病常规治疗,包括阿司匹林(生产厂家:拜耳医药保健有限公司,批準文号:国药准字J20130078,规格:100 mg)、血管紧张素转换酶抑制剂、β受体阻滞剂、他汀类等,在此基础上,对照组予以尼可地尔片(生产厂家:山西同达药业有限公司,批准文号:国药准字H14023308,规格:5 mg)治疗,15 mg/d,3次/d,三餐时口服;试验组于对照组基础上加用丹参酮ⅡA磺酸钠注射液(生产厂家:上海上药第一生化药业有限公司,批准文号:国药准字H31022558,规格:2 mL︰10 mg)80 mg/d静脉滴注。两组均连续治疗14 d。

1.3 观察指标及判定标准

1.3.1 观察比较两组治疗前后胸痛情况 包括胸痛发作频率和胸痛持续时间,均于治疗前和治疗2周后比较。

1.3.2 评估两组治疗后心电图情况 疗程结束后进行心电图疗效判定,显效:静息状态下心电图ST-T段恢复正常;有效:静息状态下心电图倒置T波变浅达50%及缺血性ST段下降,或T波转为直立;无效:心电图无明显变化[11]。总有效率=(显效例数+有效例数)/总例数×100%。

1.3.3 两组治疗前后hs-CRP水平比较 采用免疫浊度法测定两组hs-CRP水平。

1.3.4 观察比较两组治疗前后心脏功能指标 疗程结束后3个月测定两组左室射血分数(LVEF)及6 min步行试验距离。

1.4 统计学处理 采用SPSS 24.0软件对所得数据进行统计分析,计量资料用(x±s)表示,组间比较采用t检验,组内比较采用配对t检验;计数资料以率(%)表示,比较采用字2检验。以P<0.05为差异有统计学意义。

2 结果

2.1 两组一般资料比较 两组患者年龄、性别、吸烟情况、糖尿病情况、血压、低密度脂蛋白(LDL-C)、hs-CRP、心率比较,差异均无统计学意义(P>0.05),具有可比性。见表1。

2.2 两组治疗前后胸痛情况比较 治疗前,两组胸痛发作频率、持续时间比较,差异均无统计学意义(P>0.05);治疗2周后,两组胸痛发作频率、持续时间均治疗前有明显改善,且试驗组发作频率低于对照组,持续时间短于对照组,差异均有统计学意义(P<0.05),见表2。

2.3 两组治疗后心电图改善情况比较 治疗后,试验组心电图总有效率为86.67%,高于对照组的63.33%,差异有统计学意义(字2=3.859 9,P<0.05),见表3。

2.4 两组治疗前后hs-CRP水平比较 治疗后,两组hs-CRP水平均较治疗前下降,且试验组hs-CRP水平低于对照组,差异均有统计学意义(P<0.05),见表4。

2.5 两组治疗前后心脏功能指标比较 治疗前,两组LVEF、6 min步行试验距离比较,差异均无统计学意义(P>0.05)。治疗后3个月,两组LVEF、6 min步行试验距离均较治疗前明显改善,且试验组LVEF较对照组改善更显著(P<0.05)。治疗后3个月,两组6 min步行试验距离比较,差异无统计学意义(P>0.05)。见表5。

3 讨论

左主干是升主动脉根部冠状动脉窦上最大、最短、最重要的血管,发自左冠窦上,供应心脏血液的70%~75%,在整个左心系统的血供中占主导地位,因此左主干由于狭窄、堵塞等原因出现血流阻断,非常容易导致出现严重的心肌缺血,引发心肌梗死、心力衰竭或心源性休克、甚至猝死[12-14]。但目前中国尤其是中国农村偏远地区仍存在部分左主干病变患者,因拒绝或无法行PCI及CABG术而采取药物保守治疗方法,那么在常规抗血小板聚集、降脂稳斑的基础上,选择经济且疗效肯定的治疗方法来改善这部分患者的症状及生活质量至关重要。

我国传统中医药学早在《内经》中就有对“心痹”发病特点的基本认识:“胸中痛,胁支满,胁下痛”,认为治疗主要以活血化瘀为主。丹参酮ⅡA磺胺钠作为一种常见活血化瘀中药制剂,是从丹参中分离出的二萜醌类化合物丹参酮ⅡA,经磺化而得出的一种水溶性物质。研究表明,丹参酮ⅡA磺酸钠注射液主要作用机制为:(1)使纤维蛋白原裂解,生成纤维蛋白原降解产物,增加纤维蛋白原激活物活性而引起纤溶,从而降低血液D-二聚体的水平,改变血液高凝状态,抑制血栓形成;(2)升高缺氧造成的心肌细胞膜电位,降低线粒体膜电位,维持缺氧状态下两者平衡,最大限度保护心肌细胞;(3)直接激活冠状动脉平滑肌细胞激活钾通道扩张冠脉,增加心肌血流量,从而有效缓解心肌缺血现象;(4)通过抑制LDL氧化、单核细胞黏附、平滑肌细胞增殖迁移、巨噬细胞胆固醇堆积以及抑制促炎细胞因子表达等效应稳定粥样斑块[15-16]。尼可地尔是一种具有双重作用机制的药物,通过激活血管平滑肌细胞的鸟苷酸环化酶,产生类硝酸酯作用,还可通过ATP敏感的K+通道开放作用,使血管平滑肌和线粒体的K+-ATP通道开放,抑制Ca2+的内流,舒张小冠状动脉和阻力血管,增加冠状动脉血流[17-18]。

本研究显示,针对左主干病变,丹参酮ⅡA磺酸钠注射液联合尼可地尔在控制胸痛发作及改善活动耐量方面均显示出明显效果。可能有以下几个方面的原因:(1)两者均可改善心肌缺血区域侧支循环及局部供氧供血,保护心肌细胞,同时抑制血小板聚集、血栓形成,联合应用可发挥协同作用;(2)hs-CRP是作为系统性炎症的一个强有力的标志物[19],并且Meta分析表明hs-CRP>3 mg/L是心血管事件的独立危险因素[20],而丹参酮ⅡA具有显著抗炎作用,降低hs-CRP浓度可进一步有利于患者;(3)相较于传统硝酸酯类药物,尼可地尔发挥类硝酸酯作用,具备更低的耐药性,长期应用可改善患者远期生活质量。

综上所述,对左主干病变患者采用丹参酮ⅡA磺酸钠注射液联合尼可地尔治疗,可有效缓解患者胸痛症状,进一步提高临床效果及心电图疗效,显著改善患者心脏功能。然而本试验仍具有一定局限性。首先,由于冠心病患者中左主干病变占比较低,限制了更大样本量的获取。其次,部分研究对象为农村偏远地区患者,这给长期随访造成巨大困难,今后还需继续收集相关资料,开展大规模多地区的临床试验进一步证实。

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(收稿日期:2020-02-06) (本文编辑:姬思雨)

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