美国食品药品监督管理局（FDA）曾于2014年11月16日发布药物安全性通讯，提示初步试验数据显示长期抗血小板治疗的患者有临床获益，但非心血管死亡风险升高。因此FDA针对长期抗血小板治疗开展了评估工作。评估结果未发现氯吡格雷对冠状动脉疾病患者或具有冠状动脉疾病风险患者的总体死亡率存在良好或不良影响的证据，也未发现对癌症影响的证据。长期使用血液稀释药物波立维（氯吡格雷）未升高或降低心脏病患者或具有心脏病风险患者的总体死亡风险。此外，双重抗血小板治疗（DAPT）1试验和多项其他临床试验的评价结果也未表明氯吡格雷增加了癌症或癌症所致死亡的风险。

FDA同时提示由于可能导致心脏病发作和血栓风险升高，故患者不应停用氯吡格雷或其他抗血小板药物。如果对氯吡格雷有任何疑问或顾虑，请咨询医疗保健专业人士。医疗保健专业人士在开始治疗前应考虑现有抗血小板药物的获益和风险。

在双重抗血小板治疗（DAPT）的大型临床试验中，为了研究报告的氯吡格雷治疗后死亡和癌症相关死亡风险的升高，FDA审查了DAPT试验及可获得有关死亡率、癌症所致死亡或将癌症报告为不良事件等数据的其他大型长期氯吡格雷临床试验的结果^2-13。DAPT试验在行药物洗脱冠脉支架放置术患者中，将接受双重抗血小板12个月治疗（氯吡格雷[波立维]或普拉格雷[Effient]联合阿司匹林）与30个月治疗进行对比。与接受氯吡格雷12个月治疗的患者相比，接受30个月治疗的患者心脏病发作和支架血栓形成的发生率降低，但主要由癌症或外伤所致的死亡率升高。

FDA进行了荟萃分析，对其他多项长期临床试验的结果进行了研究，以评估氯吡格雷对全因死亡率的影响。结果表明，长期（≥12个月）使用氯吡格雷联合阿司匹林进行双重抗血小板治疗与短期（≤6个月）使用氯吡格雷联合阿司匹林或阿司匹林单药治疗相比，未显示改变总体死亡风险。而且，长期治疗时癌症相关死亡风险或癌症相关不良事件也未明显增加。

参考文献
1. Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Eng J Med 2014;371:2155-2166.
2. Connolly SJ, Yusuf S, Budaj A, et al. Rationale and design of ACTIVE: the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events. Am Heart J 2006;151:1187-1193.
3. Berger JS, Bhatt DL, Steg PG, et al. Bleeding, mortality, and antiplatelet therapy: results from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. Am Heart J 2011 Jul;162(1):98-105.
4. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation (CURE trial). N Engl J Med 2001 Aug 16; 345(7):494-502.
5. Steinhubl SR, Berger PB, Mann JT 3rd, et al. Clopidogrel for the Reduction of Events During Observation (CREDO): early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002 Nov 20;288(19):2411-20.
6. The SPS3 Investigators. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med 2012 Aug 30;367:817-825.
7. Lee CW, Ahn JM, Park DW, et al. Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial (DES-LATE). Circulation 2014 Jan 21;129(3):304-312.
8. Belch JJ, Dormandy J, CASPAR Writing Committee, et al. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg 2010 Oct;52(4):825-833.
9. Valgimigli M, Camp G, Monti M, et al. Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial (PRODIGY). Circulation 2012 Apr 24;125(16):2015-2026.
10. Colombo A, Chieffo A, Frasheri A, et al. Second-generation drug-eluting stent implantation followed by 6- versus 12-month dual antiplatelet therapy: the SECURITY randomized clinical trial. J Am Coll Cardiol 2014 Nov 18-25;64(20):2086-2097.
11. Feres F, Costa RA, Abizaid A, et al. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA 2013 Dec 18;310(23):2510-2522.
12. Park KW, Chae IH, Lim DS, et al. Everolimus-eluting versus sirolimus-eluting stents in patients undergoing percutaneous coronary intervention: the EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) randomized trial. J Am Coll Cardiol 2011;58(18):1844-1854.
13. Kim BK, Hong MK, Shin DH, et al. A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (Real Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol 2012 Oct 9;60(15):1340-1348.

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