抗血小板治疗出血风险控制课件

*,*,*,Click to edit Master title style,*,*,*,*,*,*,*,*,*,*,*,*,*,*,*,冠心病抗血小板治疗的出血风险控制,抗血小板治疗出血风险控制课件,抗血小板治疗出血风险控制课件,抗血小板治疗药物的演变,氯吡格雷,噻氯匹定,阿司匹林,1988,年,FDA,批准用于临床的抗血小板药物,单用疗效有限，增加剂量会增加出血危险,第一个,噻吩吡啶类,1991,年,FDA,批准,严重不良反应：中性粒细胞减少、血栓性血小板减少性紫癜,1998,年,FDA,批准,疗效、安全性被广泛证实,*,普拉格雷,*替格瑞洛,抗血小板治疗药物的演变氯吡格雷噻氯匹定阿司匹林 1988年,当代抗血小板药物治疗的发展：缺血与出血风险的平衡,抗血小板药物单药治疗,双联抗血小板药物,更强的血小板聚集抑制剂,Reduction inIschemic Events,Increase in Major Bleeds,Adapted from Gibson, AHA 2007,当代抗血小板药物治疗的发展：缺血与出血风险的平衡抗血小板药物,氯吡格雷,+ASA,双联治疗,12,个月，显著降低,NSTE-ACS,患者缺血风险达,20%,安全性：波立维,组与安慰剂组危及生命的大出血无显著差异。,Yusuf S, Zhao F, Mehta SR, et al. N Engl J Med. 2001;345(7):494-502,.,氯吡格雷+ASA双联治疗12个月，显著降低NSTE-ACS患,NSTE-ACS,患者应用氯吡格雷,+ASA,安全性良好,The CURE trial investigators. N Eng J Med.,2001;345(7,):494-502.,CURE,研究表明，与安慰剂,+ASA,相比，氯吡格雷,+ASA,导致危及生命出血或出血导致死亡的发生率无明显增加,NSTE-ACS患者应用氯吡格雷+ASA安全性良好The C,TRITON-TIMI 38,研究：普拉格雷的总体疗效与安全性,Wiviott SD, Braunwald E, McCabe CH, et al. N Engl J Med. 2007;357:2001-15.,事件率,(,),CV,死亡,/MI/,卒中,CV,死亡,非致死性,MI,非致死性卒中,(P0.001),(P=0.31),(P0.001),(P=0.93),RRR=19%,RRR=24%,疗效：,普拉格雷,显著降低,15,个月,CV,死亡,/MI/,卒中风险,(,主要缺血终点,),达,19%,；获益主要源于非致死性,MI,的降低。,TIMI,大出血,危及生命出血,非致命性出血,致命性出血,颅内出血,出血率,(,),(P=0.002),(P=0.03),(P=0.01),(P=0.23),(P=0.74),RRI=,319%,RRI=,32%,RRI=,52%,氯吡格雷,普拉格雷,出血：,普拉格雷,显著增加,非,CABG,相关,TIMI,大出血风险,(,主要安全终点,),达,32%,；包括危及生命、致命性出血等。,（非,CABG,相关出血）,TRITON-TIMI 38研究：普拉格雷的总体疗效与安全性,替格瑞洛显著降低,ACS,患者心血管事件发生危险达,16%,PLATO,研究中替格瑞洛组平均用药时间,277,天，,替格瑞洛显著降低,CV 死,亡,、MI或,卒中复合终点发生危险,16%,Days after randomisation,0,60,120,180,240,300,360,12,11,10,9,8,7,6,5,4,3,2,1,0,13,累,积发生率,(%),9.8,11.7,HR 0.84 (95% CI 0.770.92), p=0.0003,Clopidogrel,Ticagrelor,替格瑞洛显著降低ACS患者心血管事件发生危险达16%PLA,然而，代价是非,CABG,相关的大出血风险明显升高。,7,0,K-M estimated rate (% per year),9,8,6,5,4,3,2,1,Non-CABGPLATO majorbleeding,4.5,3.8,p=0.03,2.8,2.2,p=0.03,7.4,7.9,NS,5.3,5.8,NS,Ticagrelor,Clopidogrel,Non-CABGTIMI majorbleeding,CABGPLATO major bleeding,CABGTIMI major bleeding,Wallentin L et al.,New Engl J Med,.,2009;361:DOI:10.1056/NEJMoa0904327.,然而，代价是非CABG相关的大出血风险明显升高。70K,一旦出血，无论大小，都很麻烦,一旦出血，无论大小，都很麻烦,小出血临床常见，显著降低患者治疗依从性,ACS,患者,(n=396),成功置入支架，接受,ASA+,普拉格雷,1,个月,1,个月内普拉格雷总停药率,6%*,滋扰性出血,63%,内出血,33.3%,令人惊恐的出血,3.7%,1,个月内总体出血发生率,13.6%,采用,Roys,出血分类及定义：,令人惊恐的出血：颅内出血、危及生命出血或需输血。,内出血：血肿、,鼻衄、口腔出血、阴道出血、黑便、眼睛出血、血尿及呕血。,滋扰性出血：容易瘀伤、小切口出血、瘀点及瘀斑。,小出血,=,滋扰性或内出血,因滋扰性出血或,内出血停药,其他原因,停药,15.3,%,4,%,P=0.03,* 79%,为患者自发停药,小出血临床常见，显著降低患者治疗依从性ACS患者(n=396,出血后过早停用抗血小板治疗,是影响临床结局的重要因素,32.4%,发生院内出血，其中近,1/10,出院后停用任何抗血小板药物：,出院后停用抗血小板药物显著增加,6,个月死亡,/MI/,卒中风险,(,14.3% vs,用药者,7.8%,，,P0.0001,),N=26,451,，入选自,PURSUIT, PARAGON A & B,，,SYNERGY,PCI,亚组分析：,过早停用抗血小板治疗对院内,PCI,患者长期预后更具危险性,双联抗血小板治疗显著减少死亡等主要临床终点事件,Am Heart J. 2010;160:1056-1064.e2.,出血后过早停用抗血小板治疗32.4%发生院内出血，其中近1/,log rank p-value for all four categories 0.0001,log-rank p-value for no bleeding vs. mild bleeding = 0.02,log-rank p-value for mild vs. moderate bleeding 0.0001,log-rank p-value for moderate vs. severe 31,天,0.5 1 2 4 8 16 32,HR(95%CI),死亡,P,值,0.001,0.001,0.001,0.12,0.001,0.001,0.001,0.001,0.001,0.001,0.001,31,天,输血,0-1,天,2-7,天,8-30,天,31,天,HR(95%CI),ACUITY,研究中，对于,ACS,患者远期死亡的作用,再发,MI,：随时间而减弱，,30,天已无显著性,大出血和输血：存在持续影响，,1,年时仍具显著性,对,ACS,患者远期结局的持续影响,大出血,/,输血的影响更甚于缺血,Eur Heart J. 2009;30:1457-1466.,大出血 0-1天0.5 1,如何评估出血风险？,如何评估出血风险？,出血评估的有效工具出台,CRUSADE,出血评分,CRUSADE,出血评分计算器（可从,获得）,Circulation 2009;119;1873-1882,出血评估的有效工具出台 C,缺血高危因素与出血高危因素大多一致,Hector Bueno,Francisco Fernandez-Aviles. Heart 2012;98:162-168,ACS,缺血风险主要预测因素,ACS,出血风险主要预测因素,老年患者和肾功能不全等特殊人群,临床治疗尤其应重视出血与缺血平衡,缺血高危因素与出血高危因素大多一致Hector Bueno,抗血小板治疗时，如何减少出血风险？,其它抗血小板药物？,(cilostazol, vorapaxar, cangrelor ),调整,DAPT,持续时间？减少,APT,剂量？,围,PCI,过程中，何种策略减少出血风险？,消化道出血，加用,PPI,？,抗血小板治疗时，如何减少出血风险？其它抗血小板药物？(cil,抗血小板治疗时，如何减少出血风险？,其它抗血小板药物？,(cilostazol, vorapaxar, cangrelor ),调整,DAPT,持续时间？减少,APT,剂量？,围,PCI,过程中，何种策略减少出血风险？,抗血小板治疗时，如何减少出血风险？其它抗血小板药物？(cil,Cilostazol vs Asaparin,Cochrane Database Syst Rev.,2011 Jan 19;(1):CD008076.,Cilostazol vs AsaparinCochrane,Cochrane Database Syst Rev.,2011 Jan 19;(1):CD008076.,CV EVENTS,Cochrane Database Syst Rev.20,Ischaemic stroke,Cochrane Database Syst Rev.,2011 Jan 19;(1):CD008076.,Ischaemic strokeCochrane Datab,Haemorrhagic stroke,Cochrane Database Syst Rev.,2011 Jan 19;(1):CD008076.,Haemorrhagic strokeCochrane Da,MI,Cochrane Database Syst Rev.,2011 Jan 19;(1):CD008076.,MICochrane Database Syst Rev.,Vascular death,Cochrane Database Syst Rev.,2011 Jan 19;(1):CD008076.,Vascular deathCochrane Databas,Extracranial haemorrhage,Cochrane Database Syst Rev.,2011 Jan 19;(1):CD008076.,Extracranial haemorrhageCochra,GI bleeding,Cochrane Database Syst Rev.,2011 Jan 19;(1):CD008076.,GI bleedingCochrane Database S,Cilostazol+ASA vs ASA,American Heart Journal,June 2008,Cilostazol+ASA vs ASAAmerican,Revascularizatin,Revascularizatin,Restenosis,Restenosis,抗血小板治疗出血风险控制课件,Conclusion for cilostazol,NO strong evidence for Cilostazol in CHD,Stronger than ASA, maybe equivalent to TICLID,Decrease bleeding,Need more date to support its use in CHD anti-platelet therapy,Conclusion for cilostazolNO st,Vorapaxar,protease-activatedreceptor 1 antagonist,Two large scale RCT results published,Vorapaxarprotease-activatedre,Original Article,Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes (NSTEACS),Pierluigi Tricoci,M.D., Ph.D., Zhen Huang,M.S., Claes Held,M.D., Ph.D., David J. Moliterno,M.D., Paul W. Armstrong,M.D., Frans Van de Werf,M.D., Harvey D. White,D.Sc., Philip E. Aylward,M.D., Lars Wallentin,M.D., Ph.D., Edmond Chen,M.D., Yuliya Lokhnygina,Ph.D., Jinglan Pei,M.S., Sergio Leonardi,M.D., Tyrus L. Rorick,R.N., Ann M. Kilian,B.S., Lisa H.K. Jennings,Ph.D., Giuseppe Ambrosio,M.D., Ph.D., Christoph Bode,M.D., Angel Cequier,M.D., Jan H. Cornel,M.D., Rafael Diaz,M.D., Aycan Erkan,M.D., Ph.D., Kurt Huber,M.D., Michael P. Hudson,M.D., Lixin Jiang,M.D., J. Wouter Jukema,M.D., Ph.D., Basil S. Lewis,M.D., A. Michael Lincoff,M.D., Gilles Montalescot,M.D., Jos Carlos Nicolau,M.D., Ph.D., Hisao Ogawa,M.D., Matthias Pfisterer,M.D., Juan Carlos Prieto,M.D., Witold Ruzyllo,M.D., Peter R. Sinnaeve,M.D., Ph.D., Robert F. Storey,M.D., D.M., Marco Valgimigli,M.D., Ph.D., David J. Whellan,M.D., Petr Widimsky,M.D., Dr.Sc., John Strony,M.D., Robert A. Harrington,M.D., Kenneth W. Mahaffey,M.D., for the TRACER Investigators,N Engl J Med,Volume 366(1):20-33,January 5, 2012,Original Article Thrombin-Rec,Study Overview,In this trial, vorapaxar, a protease-activatedreceptor 1 antagonist that inhibits thrombin-induced platelet activation, was not effective in reducing the primary cardiovascular efficacy end point, and it increased rates of bleeding, including serious bleeding and intracranial hemorrhage.,Study OverviewIn this trial, v,Study End Points.,Tricoci P et al. N Engl J Med 2012;366:20-33,The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization,.,The prespecified key secondary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke.,Study End Points.Tricoci P et,Efficacy End Points.,Efficacy End Points.,Risk of Bleeding.,Tricoci P et al. N Engl J Med 2012;366:20-33,Risk of Bleeding.Tricoci P et,Bleeding End Points in the As-Treated Population.,Tricoci P et al. N Engl J Med 2012;366:20-33,Bleeding End Points in the As-,Conclusions,In patients with acute coronary syndromes (NSTEACS), the addition of vorapaxar to standard therapy (ASA+,Thienopyridine,) did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage.,ConclusionsIn patients with ac,Circulation. 132(20):1871-1879, November 17, 2015.,DOI: 10.1161/CIRCULATIONAHA.114.015042,Circulation. 132(20):1871-1879,background,26 449 patients over 3 years,prior MI, stroke or peripheral vascular disease,randomization to vorapaxar or placebo in addition to ASA or ASA+Thienopyridine,background26 449 patients over,2,Baseline Characteristics,2Baseline Characteristics,Characterization of Actual Thienopyridine Use From Randomization,Characterization of Actual Thi,Cardiovascular death, MI, or stroke stratified by planned thienopyridine use,Cardiovascular death, MI, or s,Efficacy end points stratified by planned thienopyridine use,Efficacy end points stratified,Bleeding End Points Stratified by Planned Thienopyridine Use,Bleeding End Points Stratified,Safety end point stratified by planned thienopyridine use,Safety end point stratified by,Net Clinical Outcome End Points Stratified by Planned Thienopyridine Use Among Patients With a Previous MI and No History of TIA or Stroke,Net Clinical Outcome End Point,approved by the FDA and EMA for reducing ischaemic events in patients with a history of MI,the benefit of vorapaxar in addition to aspirin and clopidogrel is modest and must be carefully weighed against the increase in bleeding events,Its use is contraindicated in patients with a history of cerebrovascular disease.,FDA & EMA recommendation,approved by the FDA and EMA fo,Cangrelor,Vol 382 December 14, 2013,Cangrelor Vol 382 December 14,Included studies,Vol 382 December 14, 2013,均联合应用氯吡格雷,+ASA,Included studies Vol 382 Decem,Efficacy Results,Vol 382 December 14, 2013,Efficacy Results Vol 382 Decem,Vol 382 December 14, 2013,Vol 382 December 14, 2013,Bleeding Events,Vol 382 December 14, 2013,Bleeding Events Vol 382 Decemb,Cangrelor reduced the odds of all-cause death, myocardial infarction, or ischaemia-driven revascularisation,no difference in the primary safety outcome, in GUSTO moderate bleeding,increased GUSTO mild bleeding,Conclusion for Cangrelor,Cangrelor reduced the odds of,抗血小板治疗时，如何减少出血风险？,其它抗血小板药物？,(cilostazol, vorapaxar, cangrelor ),缩短,DAPT,持续时间？减少药物剂量？,围,PCI,过程中，何种策略减少出血风险？,合并常规抗凝药物（房颤），如何处理？,抗血小板治疗时，如何减少出血风险？其它抗血小板药物？(cil,3 months,3 months,出血事件没有差别！,！,！,！,出血事件没有差别！,6 months,Circulation January 24, 2012,6 monthsCirculation January 24,1 year follow-up,，,no difference in bleeding,1 year follow-up，no difference,抗血小板治疗出血风险控制课件,Still no difference in bleeding for 1 year,Still no difference in bleedin,1 month,1 month,Duration of DAPT for 1 month,JACC VOL. 65, NO. 8, 2015,Duration of DAPT for 1 monthJA,Conclusion for shortening DAPT Duration,Logically reasonable,No direct evidence yet,ESC 2015 NSTEACS guideline,Evidence,？,Conclusion for shortening DAPT,Lowering APT dose,？,Lowering APT dose？,50mg vs 75mg clopidogrel,50mg vs 75mg clopidogrel,50mg vs 75mg clopidogrel,Because of small sample size, no difference in bleeding,50mg vs 75mg clopidogrelBecaus,Ticagrelor 60mg bid VS 90mg bid,Ticagrelor 60mg bid VS 90mg bi,PEGASUS Study,PEGASUS Study,60mg vs 90mg,，略有减少？,仅有,3,年的数据结果，更短时间是否有差异呢？,60mg vs 90mg，略有减少？仅有3年的数据结果，更短,Conclusion for lowering doses,Lower doses may decrease bleeding,Need more data to support the efficacy and safety,Conclusion for lowering dosesL,抗血小板治疗时，如何减少出血风险？,其它抗血小板药物？,调整,DAPT,持续时间？降低药物剂量？,围,PCI,过程中，何种策略减少出血风险？,(radial access, bivaludin,，,fondaparinux),抗血小板治疗时，如何减少出血风险？其它抗血小板药物？,MATRIX,Co-primary compositeoutcomes at 30 days,N=8404,NSTE-ACS + STEMI,Radial vs. femoral,Valgimigli M et al.,Lancet. 2015;385:2465-76,All-cause mortality, MI, stroke,All-cause mortality, MI, stroke, or BARC 3 or 5 bleeding,75,Speaker,MATRIXCo-primary compositeou,Radial vs femoral meta-analysis,Non-CABG major bleeeds,Death, MI, or stroke,Death,MI,Stroke,P,RR (95% CI),Valgimigli M et al.,Lancet. 2015;385:2465-76,N19 000,Radial vs femoral meta-analysi,Radial approach 2015 ESC NSTEACS Guideline,It is recommended that centres treating ACS patients implement a transition from transfemoral to transradial access.,Proficiency in the femoral approach should be maintained (e.g. for IABP insertion and structural as well as peripheral procedures),77,Radial approach 2015 ESC NSTEA,比伐卢定的优势,20,个氨基酸的肽类药物，凝血酶的直接抑制剂,与凝血酶的结合过程可控可逆,血浓度与,APTT,、,PT,和,ACT,正相关,（,r,分别为,0.77,、,0.73,和,0.8,）,不需要抗凝血酶,（,AT-,）作为辅助因子，量效关系更吻合,对血栓中和循环中的凝血酶的抑制作用几乎相同,不受激活血小板的影响,不减少血小板,比伐卢定的优势20 个氨基酸的肽类药物，凝血酶的直接抑制剂,比伐卢定,Vs,肝素,ACUITY,试验,-JAMA2007,REPLACE-2,试验,- TCT 2008,ISAR-REACT-4,试验,-AHA2011,EUROMAX,试验,-NEJM 2013,HORIZONS AMI,试验,-NEJM2006,，,TCT2008,比伐卢定Vs肝素ACUITY试验-JAMA2007,Diff =,0.0% -1.6, 1.5,RR = 0.99,0.76, 1.30,P,sup,= 0.95,Diff =,-3.3% -5.0, -1.6,RR =,0.60 0.46, 0.77,P,NI, 0.0001,P,sup, 0.0001,Diff =,-2.9% -4.9, -0.8,RR =,0.76 0.63, 0.92,P,NI, 0.0001,P,sup,= 0.005,1,endpoint,1,endpoint,Major 2,endpoint,Stone GW et al. NEJM 2008;358:2218-30,HORIZONS AMI,试验,3,602,发病 ,12,小时的,STEMI,患者,3006,例作支架分组治疗，,30,天临床结果,Diff = 0.0% -1.6, 1.5 Diff =,HORIZONS AMI,试验,3,602,发病 ,12,小时的,STEMI,患者,3006,例作支架分组治疗，,1,年随访结果,1,年净临床不良事件,TCT 2008,HORIZONS AMI 试验3,602 发病 12,HORIZONS AMI,试验,3,602,发病 ,12,小时的,STEMI,患者,3006,例作支架分组治疗，,1,年随访结果,TCT 2008,HORIZONS AMI 试验3,602 发病 12,HORIZONS AMI,试验,3,602,发病 ,12,小时的,STEMI,患者,3006,例作支架分组治疗，,3,年随访结果,The Lancet, Volume 377, Issue 9784, 2011, 2193 - 2204,Major bleeding,Cardiac mortality,Reinfarction,Stent thrombosis,HORIZONS AMI 试验3,602 发病 12,AHA 2013 STEMI guideline,AHA 2013 STEMI guideline,Bivalirudin seems to be perfect !,However,HEAT-PPCI,研究掀起波澜,Bivalirudin seems to be perfec,HEAT-PPCI,(Unfractionated Heparin versus Bivalirudin in Primary PCI),研究,-,开放、单中心、随机对照,Adeel Shahzad,，,ACC 2014,英国利物浦心胸医院，,14,名介入医生参加，历时,22,个月,1812,例,STEMI,患者随机分组,比伐卢定组,905,例患者，,751,例,(83%),造影后 行介入治疗；肝素组,907,例患者，,740,例,(82%),行介入治疗,两组,GP IIb/IIIa,抑制剂应用率相似，约,13%,30,天临床终点,Lancet. 2014 Jul 4. pii: S0140-6736(14)60924-7.,HEAT-PPCI (Unfractionated Hep,HEAT-PPCI 30,天临床终点,Outcome,Bivalirudin (%),Heparin (%),RR (95% CI),p,MACE,8.7,5.7,1.52 (1.1,2.1),0.01,Definite or probable stent thrombosis,3.4,0.9,3.91 (1.6,9.5),0.001,Major bleeding,3.5,3.1,NS,Adeel Shahzad,，,ACC 2014,HEAT-PPCI 30天临床终点Bivalirudin (,对,HEAT-PPCI,的批评,单中心,入选速度（,22,个月近,2000,例患者）,肝素用量（,70U/kg),ACT,偏低（,H-236,，,B-270),入选患者低危,再梗的判断标准,研究设计,-,知情签署晚,-,伦理？,桡动脉途径比例高与出血低有关,对HEAT-PPCI的批评单中心,NAPLES III,研究,Carlo Briguori,(Clinica Mediterranea, Naples, Italy),，,ACC 2014,830,例高出血风险（危险积分,10,）择期股动脉途径,PCI,患者,比伐卢定,Vs UFH,主要终点：院内出血,主要结果：按不同出血标准，两组均无差异,NAPLES III 研究Carlo Briguori(C,TCT 2014,TCT 2014,BRIGHT,研究,Stent Thrombosis at 30 Days,Event,Bivalirudin (n=735), n (%),Heparin (n=729), n (%),Heparin + tirofiban, n (%),p,All definite/probable stent thrombosis,4 (0.6),6 (0.9),5 (0.7),0.77,Acute (24 h),2 (0.3),2 (0.3),2 (0.3),1.00,Subacute (1,30 d),2 (0.3),4 (0.6),3 (0.4),0.66,TCT 2014,BRIGHT研究Stent Thrombosis at 30,AHA 2014 NSTE-ACS guideline,AHA 2014 NSTE-ACS guideline,Recommendations for anticoagulation in NSTE-ACS,Recommendations,Class,LOE,Parenteral anticoagulation is recommended at the time of diagnosis according to both ischaemic and bleeding risks.,I,B,Fondaparinux,(2.5 mg s.c. daily) is recommended as having the most favourable efficacysafety pro of the management strategy.,I,B,Bivalirudin,(0.75 mg/kg i.v. bolus, followed by 1.75 mg/kg/hour for up to 4 hours after the procedure) is recommended as alternative to UFH plus GPIIb/IIIa inhibitors during PCI.,I,A,UFH,70100 IU/kg i.v. (5070 IU/kg if concomitant with GPIIb/IIIa inhibitors) is recommended in patients undergoing PCI who did not receive any anticoagulan,t.,I,B,In patients on fondaparinux (2.5 mg s.c. daily.) undergoing PCI, a single i.v. bolus of UFH (7085 IU/kg, or 5060 IU/kg in the case of concomitant use of GPIIb/IIIa inhibitors) is recommended during the procedure.,I,B,Enoxaparin,(1 mg/kg s.c. twice daily) or UFH are recommended when fondaparinux is not available.,I,B,Crossover between UFH and LMWH is not recommended.,III,B,In NSTEMI patients with no prior stroke/TIA and at high ischaemic risk as well as low bleeding risk receiving aspirin and clopidogrel, low-dose rivaroxaban (2.5 mg twice daily for approximately one year) may be considered after discontinuation of parenteral anticoagulation.,IIb,B,ESC 2015 NSTE-ACS guideline,Recommendations for anticoagul,Fondaparinux,Fondaparinux,Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes,（,NSTEACS,）,The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators,N Engl J Med,Volume 354;14:1464-1476,April 6, 2006,Comparison of Fondaparinux and,Cumulative Risks of Death, Myocardial Infarction, or Refractory Ischemia (Panel A) and of Major Bleeding (Panel B) through Day 9,The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476,Cumulative Risks of Death, Myo,Main Efficacy and Safety Outcomes,The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476,Main Efficacy and Safety Outco,Cumulative Risks of Death (Panel A) and of Death, Myocardial Infarction, or Stroke (Panel B) through Day 180,The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476,Cumulative Risks of Death (Pan,Results of Subgroup Analyses of Efficacy (the Composite of Death, Myocardial Infarction, or Refractory Ischemia) (Panel A) and Safety (Major Bleeding) (Panel B) at Nine Days,The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476,Results of Subgroup Analyses o,Treatments, Complications, and Outcomes among Patients Undergoing Percutaneous Coronary Intervention (PCI) within the First Eight Days after Randomization,The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476,Treatments, Complications, and,Conclusion,Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity,ConclusionFondaparinux is simi,Recommendations for anticoagulation in NSTE-ACS,Recommendations,Class,LOE,Parenteral anticoagulation is recommended at the time of diagnosis according to both ischaemic and bleeding risks.,I,B,Fondaparinux,(2.5 mg s.c. daily) is recommended as having the most favourable efficacysafety pro of the management strategy.,I,B,Bivalirudin,(0.75 mg/kg i.v. bolus, followed by 1.75 mg/kg/hour for up to 4 hours after the procedure) is recommended as alternative to UFH plus GPIIb/IIIa inhibitors during PCI.,I,A,UFH,70100 IU/kg i.v. (5070 IU/kg if concomitant with GPIIb/IIIa inhibitors) is recommended in patients undergoing PCI who did not receive any anticoagulan,t.,I,B,In patients on fondaparinux (2.5 mg s.c. daily.) undergoing PCI, a single i.v. bolus of UFH (7085 IU/kg, or 5060 IU/kg in the case of concomitant use of GPIIb/IIIa inhibitors) is recommended during the procedure.,I,B,Enoxaparin,(1 mg/kg s.c. twice daily) or UFH are recommended when fondaparinux is not available.,I,B,Crossover between UFH and LMWH is not recommended.,III,B,In NSTEMI patients with no prior stroke/TIA and at high ischaemic risk as well as low bleeding risk receiving aspirin and clopidogrel, low-dose rivaroxaban (2.5 mg twice daily for approximately one year) may be considered after discontinuation of parenteral anticoagulation.,IIb,B,ESC 2015 NSTE-ACS guideline,Recommendations for anticoagul,抗血小板治疗出血风险控制课件,Effects of Fondaparinux on Mortality and Reinfarction in Patients With Acute ST-Segment Elevatio