【作者】 张凯；

【导师】 崔炜； 李拥军；

【作者基本信息】 河北医科大学 ， 内科学， 2008， 硕士

【摘要】 目的:冠状动脉性心脏病(CHD)是中老年人最常见的疾病之一,也是导致人类疾病死亡的首位原因,经皮冠状动脉介入术(PCI)是治疗CHD的一个很常用的治疗方法。PCI术中的抗凝非常重要,通常应用普通肝素(UFH),静注普通肝素抗凝的敏感性及肝素的代谢存在着很大的个体差异,肝素进入血流与多种血浆蛋白结合后,其抗凝活性减少到一个低水平,肝素还与内皮细胞以及巨噬细胞相结合,这使其药效动力学和药代动力学变得复杂而难以预测。低分子肝素(LMWH)与巨噬细胞和内皮细胞结合较少,不易被血小板第四因子灭活,很少与血浆蛋白结合,由于它的内在优点使其在很多的抗凝领域里取代了UFH。随着低分子肝素的大规模应用已经有许多临床研究显示其可能在择期PCI中替代普通肝素来进行抗凝治疗。PCI手术可以导致术后肌钙蛋白(cTnI)、肌酸激酶同工酶(CK-MB)和肌红蛋白(MYO)不同程度的升高,术中使用抗凝药物可以减轻手术操作对心肌的损伤,本研究的目的在于通过对比在择期PCI中使用UFH和LMWH对术后cTnI,CK-MB和Myo升高的影响,进一步探讨冠心病患者行择期经皮冠状动脉介入治疗(PCI)中应用低分子量肝素替代普通肝素的可行性和有效性。方法:2006年5月至2007年11月间在我院心血管内科住院拟行择期PCI术的急性冠脉综合症(Acute CoronarySyndrome,ACS)患者共106例。随机分为2组:注射普通肝素组(54例),达肝素钠组(52例),其中男性87例,女性19例;年龄在37～77岁之间,平均56.29±9.92岁。所有患者术前均应用肠溶阿司匹林75～150mg每日1次;氯吡格雷(商品名:波力维,塞诺菲圣德拉堡制药有限公司)75 mg每日1次;PCI术前上述药物至少3天。所有患者术前均常规应用肠溶阿司匹林75～150 mg每日1次;氯吡格雷75 mg每日1次;达肝素钠(Dalteparin,法安明/Fragmin) 5000IU皮下注射每12小时1次,各至少3天,手术前12小时内停用达肝素钠皮下注射1次。普通肝素组在PCI术前经动脉鞘管注入普通肝素5000IU,冠脉造影完成后再将肝素补充至10000IU;达肝素钠组直接将5000IU达肝素钠一次性经鞘管内注射,冠脉造影完成后再补充达肝素5000IU。分别于用药前及手术结束后20小时采集血样送检。根据术后ACT水平对于经股动脉途径手术者,普通肝素组在PCI术后4小时左右拔除动脉鞘管,达肝素钠组在注射达肝素钠后2～4小时拔除动脉鞘管。对于经桡动脉途径手术者,均在手术后即可拔出鞘管。术前及术后20小时采集血样检测cTnI、CK-MB和MYO。统计学分析:这只是一个初步的试验研究,无法得出有统计学意义的临床终点结果,我们一共采集数据106例,所有计数资料都以平均数±标准差( x±s)或者率(%)表示,计数资料采用独立样本的t检验,计量资料使用χ2检验。结果:术前UFH组和LMWH组cTnI结果均为正常(<1.0 ng/ml)。术后UFH组cTnI阳性为20例(37.03%),LMWH组cTnI阳性为16例(30.77%);两组间无显著性差异(P=0.634)。UFH组中,肌钙蛋白升高三倍者为6例(11.11%);LMWH组中,肌钙蛋白升高三倍者4例(7.69%);两组间亦无统计学差异(P=0.787) (Table 3, Fig 1)。术后UFH组cTnI为1.86±3.00 ng/ml,LMWH组为1.54±3.95 ng/ml。(P=0.679)术前UFH组和LMWH组CK-MB结果均为正常(<5 ng/ml)。术后UFH组CK-MB阳性31例(57.40%),LMWH组CK-MB阳性23例(44.23%),两组间无显著性差异(P=0.245)。UFH组中,CK-MB升高3倍者12例(22.22%),LMWH组中CB-MB升高3倍者6例(11.54%)。两组间亦无统计学差异(P=0.228)( Table 4, Fig 2)。术后UFH组CK-MB为26.56±62.95ng/ml,LMWH组为8.98±13.62ng/m(lP=0.030)。术前UFH组和LMWH组MYO结果均为正常(<70ng/ml)。术后UFH组MYO阳性1例(1.85%),LMWH组阳性2例(3.84%),两组之间无显著性差异(P=0.974)。结论:在择期PCI术中,低分子肝素—达肝素钠至少具有和普通肝素相同的安全性;值得在大规模临床研究中进一步研究、证实。更多还原

【Abstract】 Objective: Coronary heart disease (CHD) is one of the usual diseases disturbing wrinkly and elderly people, and recognized as the first killer. Recently, in the treatment of Percutaneous Coronary Intervention (PCI), as a popular treatment to CHD, anticoagulation is a very important step. Generally, Unfractionated Heparin (UFH) is used as the first choice of anticoagulation. However, the sensitiveness and metabolism of UFH differ with different patients. Entering into the blood, UFH integrates with kinds of Plasma protein, making itself less active in anticoagulatory activity; at the same time, UFH may integrate with endothelial cells and macrophage, making it even harder for us to test its pharmacodynamics and pharmacokinetics. Low Molecular Weight Heparin (LMWH) is now used as a substitution of UFH in the treatment of anticoagulation. Few LMWH integrates with macrophage and endothelial cell, and it seldom fuses with plasma protein, making itself surviving the attack of platelet factor 4. All these advantages make LMWH the first choice in the treatment of anticoagulation instead of UFH. Many prospective, controlled clinical trials have investigated the use of LMWH vs. UFH in the treatment of PCI. PCI treatment might cause the by-effect of elevation of cTnI and CK-MB in certain patients, therefore, anticoagulant is presenting to the patients in order to alleviate the damage caused by PCI operation.The research focuses on influence of LMWH vs. UFH on the elevation of cTnI, CK-MB and MYO in the treatment of PCI, probing into the possibility and stability of large scale use of LMWH instead of UFH in the treatment of PCI.Methods: From May 2006 to November 2007, 106 patients with CHD who were planned to undergo elective PCI were enrolled into this study. The 106 patients were randomized to UFH group (54 cases) and LMWH group (52 cases); the age of the subjects is between 37-77, with an average age of 56.29±9.92. Before the treatment of PCI, all the subjects take a regular use of Aspirin 75-150mg once a day, Clopidogrel 75 mg once a day, a regular use of 5000 IU Dalteparin subcutaneously once every 12 hours. Subcutaneous Fragmin (5000 IU,q12 h) given to both groups last at least 3 days until 12 hours before PCI. In the UFH group, patients were given UFH 5000 IU firstly before selective coronary angiography, additional 5000 IU was given before PCI procedure. In the LMWH group, patients received dalteparin 10000 IU before PCI. For patients with a transradial approach, the sheath was withdrawn immediately after PCI; for patients with a transfemoral approach, the sheath was withdrawn about 4 hours after the procedure. Blood samples were collected respectively before the treatment and 20 hours after PCI for the test of the changes of cTnI, CK-MB and MYO of the subjects.Statistical analysis, because this was a pilot study, it was not adequately powered to detect statistical significance in clinical end points. However, we estimated a priori that randomization of 106 patients overall would provide feasibility data for design of larger studies. All data are expressed as mean value±SD or frequency (%), unless otherwise stated. Analyses of outcome variables (individual or composite) were performed on an intention-to-treat basis using 2-tailed independent t test for continuous variables and either theχ2 test or Fisher exact test for noncontinuous variables.Results: Before the PCI, cTnI were normal in UFH group and LMWH group (<1.00 ng/ml). The incidence of total cTnI≥1.00 ng/ml was 37.03% in the UFH group and 30.77% in the LMWH group after PCI. There were no significant difference between the two groups (P=0.634). The incidence of total cTnI≥3.00 ng/ml was 11.11% in the UFH group and 7.69% in the LMWH group. There were no significant difference between the two groups (P=0.787).Before the PCI, CK-MB were normal in UFH group and LMWH group (<5.00ng/ml). The incidence of total CK-MB≥5.00 ng/ml was 57.40% in the UFH group and 44.23% in the LMWH group after PCI. There were no significant difference between the two groups (P=0.245). The incidence of total cTnI≥15.00 ng/ml was 22.22% in the UFH group and 11.54% in the LMWH group. There were no significant difference between the two groups (P=0.228).Before the PCI, MYO were normal in UFH group and LMWH group (<70.00 ng/ml). The incidence of total MYO≥70.00 ng/ml was 1.85% in the UFH group and 3.84% in the LMWH group after PCI. There were no significant difference between the two groups (P=0.228).With the UFH group, after the subcutaneous 10000 IU was finished, blood test of the plasma anti-Xa level was conducted respectively at 10min, 20min, and 1huor, with the result listed correspondingly as 0.32±0.14 IU/ml, 0.74±0.15IU/ml and 0.82±0.12IU/mlWith the LMWH group, after the subcutaneous 10000 IU was finished, blood test of the plasma anti-Xa level was conducted respectively at 10min, 20min, and 1huor, with the result listed correspondingly as 0.28±0.12 IU/ml、0.67±0.15 IU/ml and 0.72±0.12 IU/ml.Conclusions: In this pilot, randomized comparison of Fragmin with UFH in patients undergoing elective PCI is at least as safe and efficacious as UFH; these data form the basis for further evaluation of Fragmin in a larger number of patients in this setting.更多还原