西洛他唑与氯吡格雷联合治疗对非ST 段抬高急性冠脉综合征血小板膜糖蛋白的影响

摘要/Abstract

摘要： 目的:评价联合抗血小板治疗方案的有效性及安全性, 以探讨西洛他唑+氯吡格雷联合治疗非ST 段抬高急性冠脉综合征(NSTE-ACS) 患者的应用价值。方法:将63 例确诊为NSTE-ACS 的患者, 随机分为两组, A 组(31 例): 口服西洛他唑100 mg bid +氯吡格雷75 mg qd; B 组(32 例): 口服阿司匹林100 mg qd +氯吡格雷75 mg qd 。利用流式细胞术分别检测治疗前、治疗第7、 14 天的血小板膜糖蛋白[纤维蛋白原受体(PAC-1) 和P 选择素(CD62P) ] 的表达率, 计算并比较其抑制率,观察治疗过程中主要不良心脏事件(MACE) 发生率、出血并发症。结果:两组PAC-1 或CD62P 的表达率在治疗第7、 14 天均较治疗前明显下降(P<0. 01), 第14 天最显著。治疗前, 治疗第7、 14天A 组和B 组同期的PAC-1、 CD62P 表达率之间差异无统计学意义(P >0. 05); 两组在相同治疗时间点对PAC-1、 CD62P 抑制率差异无统计学意义(P <0. 05); 两组MACE 发生率对比无统计学差异(P <0. 05), A 组的出血并发症明显少于B组(P <0. 05) 。结论:对NSTE-ACS 患者, 西洛他唑+氯吡格雷对血小板抑制的近期效果与阿司匹林+氯吡格雷方案相似, 且安全性更好。

关键词: 西洛他唑, 氯吡格雷, 流式细胞术, 血小板膜糖蛋白

Abstract: AIM:To evaluate the efficacy and safety of the antiplatelet agent cilostazol combinated with clopidogrel in patients with acute coronary artery syndrome without ST-segment elevation(NSTE-ACS). METHODS:63 patients with NSTE-ACS were randomly divided into tow groups. Group A(n =31) received cilostazol (100 mg bid) plus clopidogrel (75 mg once daily), Group B(n =32) received aspirin (100 mg once daily) plus clopidogrel (75 mg once daily), the treatment course was 14 days. The expression and inhibition rates of platelet membrane glycoprotein (PAC-1 and CD62P)were measured by flow cytometry before anti-platelet therapy, 7 days and 14 days after initial therapy. The major adverse cardiac event and bleeding complication were monitored. RESULTS: There are lower expression rate at 7 days and 14 days after initial therapy than before therapy in both two groups(P <0. 01), the lowest at 14 days after initial therapy. The expression levels of PAC-1 or CD62 had no significant difference between two groups in the same time point(P <0. 05); Inhibition rates of PAC-1 or CD62 had also no significant difference beween two groups in the same time point (P >0. 05). Moreover, there was no statistically significant difference in occurrence rate of major adverse cardiac event (MACE) between these two groups(P <0. 05) while Group A had less hemorrhage complications than Group B (P < 0. 05). CONCLUSION:For patients with NSTEACS, anti-platelet efficiency of cilostazol plus clopidogrel are similar to aspirin plus clopidogrel whereas the previous is safer.

Key words: cilostazol, clopidogrel, f low cytometry, platelet membrane glycoprotein

中图分类号:

韦建瑞, 李彪, 黎庆梅, 郭壮波, 吴沃栋. 西洛他唑与氯吡格雷联合治疗对非ST 段抬高急性冠脉综合征血小板膜糖蛋白的影响[J]. 中国临床药理学与治疗学, 2008, 13(5): 557-562.

WEI Jian-rui, LI Biao, LI Qing-mei, GUO Zhuang-bo, WU Wo-dong. Effects of cilostazol combinated with clopidogrel on platelet membrane glycoprotein in patients with acute coronary artery syndrome without ST-segment elevation[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(5): 557-562.

参考文献

[1] Sorkin EM, Markham A.Cilostazol[J]. Drugs Aging, 1999, 14(1): 63-67; discussion 72-73.
[2] 张文超, 韦建瑞, 蒋作锋, 等.流式细胞术检测阿司匹林对冠心病患者血小板活化标志物的影响[J]. 中国医院药学杂志, 2007, 27(2): 164-167.
[3] Kamath S, Blann AD, Lip GY.Platelet activation:assessment and quantification[J]. Eur Heart J, 2001, 22(17): 1561-1571.
[4] Mcever RP.The clinical significance of platelet menbrane grycoproteins Hernatology/ oncology [J]. Clin North Am, 1990, 4(1): 87.
[5] Stenberg PE, McEver RP, Shu man MA, et al.A platelet plasma after aetivation[J]. J Cell Biol, 1985, 101(3): 880.
[6] Metzelaar MJ, Heijnen HF, Six ma JJ, et al.Identification of a 33-Kd protein associated with the alpha-granule membrane(GMP-33) that is expressed on the surface of activated platelets[J]. Blood, 1992, 79(2): 372.
[7] Michelson AD, Barmard MR, Krueger LA, el al. Evaluation of plateletfunction by flow, cytometry [J]. Methods, 2000, 21(2): 259-270.
[8] Giles H, Smith RE, Martin JF.Platelet glycoproteinⅡ b/Ⅲ a and size are increased in acute myocardial infarction [J]. Eur J Clin Invest, 1994, 24(1): 69-72.
[9] 吴庆华, 唐小斌, 陈忠, 等.西洛他唑治疗肢体动脉缺血性疾病的临床疗效观察[J]. 心血管病杂志, 1997, 16 (3) 211-214.
[10] J IshizaK_a N, Taguehi J, Kimura Y, et al.Effects of a single local adIllinistration of cilostazol on neointimal formation in balloon-injured rat carotid artery[J]. Atherosehrosis, 1999, 142(1): 41-46.
[11] Kunishima T, Musha H, Eto F, et al. A randomized trial of aspirin versus cilostazol therapy after successful coronary stent implantation[J]. Clin Ther, 1997, 19(5): 1058- l066.
[12] Kozuma K, Hara K, Yamasaki M, et a1.Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation[J]. Am Heart J, 2001, 141(1): 124-130.
[13] Park SW, Lee CW, Kim HS, et al.Effects of cilostazol on angiographic restenosis after coronary stent placement [J]. Am J Cardiol, 2000, 86(5): 499-503.
[14] SekiguehiM, Hoshizaki H, Adaehi H, et al.Effects of antiplatelet agents on subacute thrombosis and restenosis after successful coronary stenting: a randomized comparison of ticlopidine and cilostazol[J]. Circ J, 2004, 68(7): 610- 614.
[15] Park SJ, Shim WH, Ho DS, et al. A paclitaxel-eluting stent for the prevention of coronary restenosis[J]. N Engl J Med, 2003, 348(16): 1537-1545.
[16] Douglas Jr JS, Holmes Jr DR, Kereiakes D.Cilostazol for restenosis trial:a randomized.double-blind study following coronary artery stent implantation.Late Breaking Clinical Trial Abstracts, AlIA, 2003 [J]. Circulation, 2003, 108 (21): 2723
[17] 韩雅玲, 苏庆丰, 李毅, 等.冠状动脉介入治疗术后三联抗血小板治疗的近期疗效[J]. 中华医学杂志, 2006, 86(16): 1093-1096.
[18] CAPRIE Steering Committee. A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE)[J]. Lancet, 1996, 348(9038): 1329-1339.
[19] Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled tria1 [J]. MA, 2002, 288(19): 24l1-2420.
[20] Yusuf S, Zhao F,Mehta SR, et a1. Effects of elopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation[J]. N Engl J Med, 2001, 345(7): 494-502.
[21] 郭壮波, 韦建瑞, 张文超, 等.流式细胞术检测冠心病患者血小板表面糖蛋白的变化[J]. 广州医药, 2007, 38(1): 17-19.