不稳定型心绞痛的治疗进展
作者：吕钰 吕新华 耿君 董丽华
单位：山东省滨州地区医院(256610)
关键词：
中国综合临床000102 不稳定型心绞痛(UAP)是介于劳累性稳定型心绞痛与急性心肌梗死(AMI)和猝死之间的临床表现。主要包括①初发心绞痛，②恶化劳力性心绞痛，③静息心绞痛伴心电图缺血改变，④心肌梗死后早期心绞痛[1]。由于它具有独特的病理生理机制及临床预后，如果不能恰当及时的治疗，患者可能发展为AMI，甚至猝死，故加强对UAP治疗至关重要。近年来对UAP的治疗研究较多，综述如下。
1药物治疗
1.1抗血小板治疗
1.1.1阿斯匹林阿斯匹林通过抑制环氧化酶，使血栓素A2(TXA2)的合成减少，从而抑制血栓的形成。在心肌梗死和死亡危险性研究(RISC)[2]，中，UAP患者服用阿斯匹林每日75mg，结果用药5天病死率和AMI发生率从5.7%降至2.5%，危险性下降57.0%；30天时从13.3%降至4.2%；3个月时从17.0%降至6.5%。Theroux等[3]观察一组UAP急性期患者，随机给阿斯匹林和安慰剂，结果6天时阿斯匹林组AMI的发生率为2.5%，而对照组为6.4%，危险性下降63.0%。美国退伍军人管理局的研究表明阿斯匹林治疗的UAP组致命性和非致命性AMI的发生率从10.1%降至5.0%。随访1年，阿斯匹林组的病死率仍较对厢组下降43.0%(5.5%比9.5%)，提示病变过程已获控制[4]。对于阿斯匹林的最佳剂量目前尚不清楚，国内推荐剂量为每日80～325mg。
, 百拇医药
1.1.2血小板膜糖蛋白Ⅱb/Ⅲ.(GPⅡb/Ⅲa)受体拮抗剂包括GPⅡb/Ⅲa受体单克隆抗体如C7E3，合成的肽类制剂如Intigrelin和合成的非肽类制剂如Lamifiban和噻氯吡啶(ticlopidine)等。药理作用：作用于血小板膜GPⅡb/Ⅲa受体这一血小板聚集的中心环节，从根本上抑制血小板聚集反应。一项1200例UAP患者的多个临床试验[5]综合显示，GPⅡb/Ⅲa受体拮抗剂使UAP患者心脏事件(包括冠心病死亡，非致死性AMI和顽固性心绞痛)发生率下降了40.0%～50.0%。加拿大对Lamifiban的研究[6]，包括了15个中心的365例UAP患者，随机1次给予Lamifiban静脉150～750μg/kg后连续72～120小时静脉滴注1～5μg/(ks·min)加口服阿斯匹林325mg/d或仅给阿斯匹林治疗。与对照组比较，Lamifiban治疗组用药期间和1个月内冠心病死亡、非致命性AMI、紧急冠脉血管再建术均显著减少(P<0.05)，非颅内和非威胁生命的出血为21.9%，对照组为0.8%。Balsano等[7]研究652例UAP患者，在人院后48小时内，随机给予噻氯吡啶250mg，2次/d或对照剂，随访6个月，噻氯吡啶使致死性和非致死性的AMI发生率从13.6%降至7.3%，危险性下降46.3%。该类药物中虽然噻氯吡啶和C7E3已在临床应用，但大规模前瞻性临床研究仍在进行，以进一步了解其剂量、疗效和安全性等关系。……
, 百拇医药
参考文献：
[1]Gerstenblith G. Treatment of unstable angina pectoris. Am J Cardioi, 1992, 70(14): 32G.
[2]The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary disease, lancet, 1990, 336(8719): 827
[3]Theroux P, Quimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med, 1988, 319(19): 1105
, http://www.100md.com
[4]Lewis HD, Davis JW, Archibald DG, et al. Proteetive effects of aspirin against myocaridial infarction and death in men with unstable angina. N Engl J Meal, 1983, 309(4): 396
[5]Frans VW. Intematiunal workshop on antithrombotic therapy for acute coronary syndromes. Circulation, 1996, 94(3): 593
[6]Theroux P, Kouz S, Knudtson M, et al. Platelet membrane receptor clycopmtein Ⅱb/Ⅲ, antagonism in unstable angina, the canadian lamifiban study. Circulation, 1996, 94(4): 899
, http://www.100md.com
[7]Balaano F, Rizzun P, Viuli F, et al. Antiplatelet treatment with diciopidine in unstable angins. Controlled mulitcenter clinical trial. Circulation, 1990, 82(1): 17
[8]Theroux P, Waters D, Lam J, et al. Reactivation of unstable angina following discontinuation of heparin. N Engl J Med, 1992, 327 (3):141
[9]Topoi EJ, Fuster V, Harrington KA, et al. Recombinant hirudin for unstable angina pectoris: a multicenter, randomized angiographic trial. Circulation, 1994, 89(4): 1557
, http://www.100md.com
[10]Waters D, Lam J. Is thrombolytic therapy striking out in unstable angina?Circulation, 1992, 86(5): 1642
[11]Anderson HV, Cannon CP, Grudy SC, et al. One-year results of thrombolysis in myocardial infarctiun(TIMI) Ⅲ B clinical trial: a randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction. JACC, 1995, 26 (8):1643
, 百拇医药
[12]Arbustini E, Servi SD. Bramucci E, et al. Comparison of coronary lesions obtained by directional coronary atherectomy in unstable angina,stable angina and restenosis is after either atherectomy or angioglasty. Am J Cardiol, 1995, 75 (4): 675
[13]吕钰.小剂量尿激酶治疗难治性不稳定心绞痛94例临床观察.中国综合医学，1994，2(2)：192
[14]Romeo F, Rosano GMC, Martuscell E, et al. Effectiveness of prolonged low dose recombinant tissue - type plasmigen activator for refractory unstableangina. JACC, 1995, 25(6): 1295
[15]Serrugs PW, Deckers JVV, Close P, et al. Adouble - blindrandomized heparin controlled trial evaluating acute and long-term efficoncy of γ-hirudin(CGP38, 393) in patients undergoing coronary angioplasry. Circulation, 1994, 90(4) (Pt2): 1-394
收稿日期：1998-09-11
修稿日期：1999-08-18, 百拇医药
单位：山东省滨州地区医院(256610)
关键词：
中国综合临床000102 不稳定型心绞痛(UAP)是介于劳累性稳定型心绞痛与急性心肌梗死(AMI)和猝死之间的临床表现。主要包括①初发心绞痛，②恶化劳力性心绞痛，③静息心绞痛伴心电图缺血改变，④心肌梗死后早期心绞痛[1]。由于它具有独特的病理生理机制及临床预后，如果不能恰当及时的治疗，患者可能发展为AMI，甚至猝死，故加强对UAP治疗至关重要。近年来对UAP的治疗研究较多，综述如下。
1药物治疗
1.1抗血小板治疗
1.1.1阿斯匹林阿斯匹林通过抑制环氧化酶，使血栓素A2(TXA2)的合成减少，从而抑制血栓的形成。在心肌梗死和死亡危险性研究(RISC)[2]，中，UAP患者服用阿斯匹林每日75mg，结果用药5天病死率和AMI发生率从5.7%降至2.5%，危险性下降57.0%；30天时从13.3%降至4.2%；3个月时从17.0%降至6.5%。Theroux等[3]观察一组UAP急性期患者，随机给阿斯匹林和安慰剂，结果6天时阿斯匹林组AMI的发生率为2.5%，而对照组为6.4%，危险性下降63.0%。美国退伍军人管理局的研究表明阿斯匹林治疗的UAP组致命性和非致命性AMI的发生率从10.1%降至5.0%。随访1年，阿斯匹林组的病死率仍较对厢组下降43.0%(5.5%比9.5%)，提示病变过程已获控制[4]。对于阿斯匹林的最佳剂量目前尚不清楚，国内推荐剂量为每日80～325mg。
, 百拇医药
1.1.2血小板膜糖蛋白Ⅱb/Ⅲ.(GPⅡb/Ⅲa)受体拮抗剂包括GPⅡb/Ⅲa受体单克隆抗体如C7E3，合成的肽类制剂如Intigrelin和合成的非肽类制剂如Lamifiban和噻氯吡啶(ticlopidine)等。药理作用：作用于血小板膜GPⅡb/Ⅲa受体这一血小板聚集的中心环节，从根本上抑制血小板聚集反应。一项1200例UAP患者的多个临床试验[5]综合显示，GPⅡb/Ⅲa受体拮抗剂使UAP患者心脏事件(包括冠心病死亡，非致死性AMI和顽固性心绞痛)发生率下降了40.0%～50.0%。加拿大对Lamifiban的研究[6]，包括了15个中心的365例UAP患者，随机1次给予Lamifiban静脉150～750μg/kg后连续72～120小时静脉滴注1～5μg/(ks·min)加口服阿斯匹林325mg/d或仅给阿斯匹林治疗。与对照组比较，Lamifiban治疗组用药期间和1个月内冠心病死亡、非致命性AMI、紧急冠脉血管再建术均显著减少(P<0.05)，非颅内和非威胁生命的出血为21.9%，对照组为0.8%。Balsano等[7]研究652例UAP患者，在人院后48小时内，随机给予噻氯吡啶250mg，2次/d或对照剂，随访6个月，噻氯吡啶使致死性和非致死性的AMI发生率从13.6%降至7.3%，危险性下降46.3%。该类药物中虽然噻氯吡啶和C7E3已在临床应用，但大规模前瞻性临床研究仍在进行，以进一步了解其剂量、疗效和安全性等关系。……
, 百拇医药
参考文献：
[1]Gerstenblith G. Treatment of unstable angina pectoris. Am J Cardioi, 1992, 70(14): 32G.
[2]The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary disease, lancet, 1990, 336(8719): 827
[3]Theroux P, Quimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med, 1988, 319(19): 1105
, http://www.100md.com
[4]Lewis HD, Davis JW, Archibald DG, et al. Proteetive effects of aspirin against myocaridial infarction and death in men with unstable angina. N Engl J Meal, 1983, 309(4): 396
[5]Frans VW. Intematiunal workshop on antithrombotic therapy for acute coronary syndromes. Circulation, 1996, 94(3): 593
[6]Theroux P, Kouz S, Knudtson M, et al. Platelet membrane receptor clycopmtein Ⅱb/Ⅲ, antagonism in unstable angina, the canadian lamifiban study. Circulation, 1996, 94(4): 899
, http://www.100md.com
[7]Balaano F, Rizzun P, Viuli F, et al. Antiplatelet treatment with diciopidine in unstable angins. Controlled mulitcenter clinical trial. Circulation, 1990, 82(1): 17
[8]Theroux P, Waters D, Lam J, et al. Reactivation of unstable angina following discontinuation of heparin. N Engl J Med, 1992, 327 (3):141
[9]Topoi EJ, Fuster V, Harrington KA, et al. Recombinant hirudin for unstable angina pectoris: a multicenter, randomized angiographic trial. Circulation, 1994, 89(4): 1557
, http://www.100md.com
[10]Waters D, Lam J. Is thrombolytic therapy striking out in unstable angina?Circulation, 1992, 86(5): 1642
[11]Anderson HV, Cannon CP, Grudy SC, et al. One-year results of thrombolysis in myocardial infarctiun(TIMI) Ⅲ B clinical trial: a randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction. JACC, 1995, 26 (8):1643
, 百拇医药
[12]Arbustini E, Servi SD. Bramucci E, et al. Comparison of coronary lesions obtained by directional coronary atherectomy in unstable angina,stable angina and restenosis is after either atherectomy or angioglasty. Am J Cardiol, 1995, 75 (4): 675
[13]吕钰.小剂量尿激酶治疗难治性不稳定心绞痛94例临床观察.中国综合医学，1994，2(2)：192
[14]Romeo F, Rosano GMC, Martuscell E, et al. Effectiveness of prolonged low dose recombinant tissue - type plasmigen activator for refractory unstableangina. JACC, 1995, 25(6): 1295
[15]Serrugs PW, Deckers JVV, Close P, et al. Adouble - blindrandomized heparin controlled trial evaluating acute and long-term efficoncy of γ-hirudin(CGP38, 393) in patients undergoing coronary angioplasry. Circulation, 1994, 90(4) (Pt2): 1-394
收稿日期：1998-09-11
修稿日期：1999-08-18, 百拇医药