抗血小板治療的出血風(fēng)險(xiǎn)控制ppt課件

1、冠心病抗血小板治療的出血風(fēng)險(xiǎn)控制 抗血小板治療藥物的演變噻氯匹定噻氯匹定阿司匹林阿司匹林l 1988年FDA批準(zhǔn)用于臨床的抗血小板藥物l單用療效有限，增加劑量會(huì)增加出血危險(xiǎn)l 第一個(gè)噻吩吡啶類 l 1991年FDA批準(zhǔn)l 嚴(yán)重不良反應(yīng)：中性粒細(xì)胞減少、血栓性血小板減少性紫癜l(fā) 1998 1998年年FDAFDA批準(zhǔn)批準(zhǔn)l 療效、安全性被廣泛證實(shí)療效、安全性被廣泛證實(shí)*普拉格雷普拉格雷*替格瑞洛替格瑞洛氯吡格雷氯吡格雷+ASA雙聯(lián)治療雙聯(lián)治療12個(gè)月，顯著降低個(gè)月，顯著降低NSTE-ACS患者缺血風(fēng)險(xiǎn)達(dá)患者缺血風(fēng)險(xiǎn)達(dá)20%安全性：波立維組與安慰劑組危及生命的大出血無(wú)顯著差異。Yusuf S, Z

2、hao F, Mehta SR, et al. N Engl J Med. 2001;345(7):494-502. The CURE trial investigators. N Eng J Med. 2001;345(7):494-502.u CURE研究表明，與安慰劑+ASA相比，氯吡格雷+ASA導(dǎo)致危及生命出血或出血導(dǎo)致死亡的發(fā)生率無(wú)明顯增加TRITON-TIMI 38研究：普拉格雷的總體療效與安全性研究：普拉格雷的總體療效與安全性Wiviott SD, Braunwald E, McCabe CH, et al. N Engl J Med. 2007;357:2001-15.事件率(

3、)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%療效：普拉格雷顯著降低15個(gè)月CV死亡/MI/卒中風(fēng)險(xiǎn)(主要缺血終點(diǎn))達(dá)19%；獲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顱內(nèi)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：普拉格雷顯著增加非CABG相關(guān)TIMI大出血風(fēng)險(xiǎn)(主要安全終點(diǎn))達(dá)32%；包括危及生命、致命性出血等。（非CABG相關(guān)出血）替格

4、瑞洛顯著降低ACS患者心血管事件發(fā)生危險(xiǎn)達(dá)16%PLATO研究中替格瑞洛組平均用藥時(shí)間277天，替格瑞洛顯著降低CV 死亡、MI或卒中復(fù)合終點(diǎn)發(fā)生危險(xiǎn)16%Days after randomisation060120180240300360121110987654321013累累積發(fā)生率積發(fā)生率 (%)9.811.7HR 0.84 (95% CI 0.770.92), p=0.0003ClopidogrelTicagrelor然而，代價(jià)是非CABG相關(guān)的大出血風(fēng)險(xiǎn)明顯升高。70K-M estimated rate (% per year)98654321Non-CABGPLATO majorb

5、leeding4.53.8p=0.032.82.2p=0.037.47.9NS5.35.8NSTicagrelorClopidogrelNon-CABGTIMI majorbleedingCABGPLATO major bleedingCABGTIMI major bleedingWallentin L et al. New Engl J Med.2009;361:DOI:10.1056/NEJMoa0904327.一旦出血，無(wú)論大小，都很麻煩小出血臨床常見，顯著降低患者治療依從性小出血臨床常見，顯著降低患者治療依從性ACS患者(n=396)成功置入支架，接受ASA+普拉格雷1個(gè)月1個(gè)月內(nèi)普拉

6、格雷總停藥率個(gè)月內(nèi)普拉格雷總停藥率6%*滋擾性出血滋擾性出血 63%內(nèi)出血內(nèi)出血 33.3%令人驚恐的出血 3.7%1個(gè)月內(nèi)總體出血發(fā)生率個(gè)月內(nèi)總體出血發(fā)生率13.6%采用Roys出血分類及定義： 令人驚恐的出血：顱內(nèi)出血、危及生命出血或需輸血。 內(nèi)出血：血腫、鼻衄、口腔出血、陰道出血、黑便、眼睛出血、血尿及嘔血。 滋擾性出血：容易瘀傷、小切口出血、瘀點(diǎn)及瘀斑。小出血=滋擾性或內(nèi)出血因滋擾性出血或因滋擾性出血或內(nèi)出血停藥內(nèi)出血停藥 其他原因其他原因停藥停藥 15.3%4%P=0.03* 79%為患者自發(fā)停藥出血后過早停用抗血小板治療是影響臨床結(jié)局的重要因素32.4%發(fā)生院內(nèi)出血，其中近1/10

7、出院后停用任何抗血小板藥物：出院后停用抗血小板藥物顯著增加6個(gè)月死亡/MI/卒中風(fēng)險(xiǎn)(14.3% vs 用藥者7.8%，P0.0001)N=26,451，入選自PURSUIT, PARAGON A & B，SYNERGYPCI亞組分析：過早停用抗血小板治療對(duì)院內(nèi)PCI患者長(zhǎng)期預(yù)后更具危險(xiǎn)性雙聯(lián)抗血小板治療顯著減少死亡等主要臨床終點(diǎn)事件Am Heart J. 2010;160:1056-1064.e2.log rank p-value for all four categories 0.0001log-rank p-value for no bleeding vs. mild bleeding

8、= 0.02log-rank p-value for mild vs. moderate bleeding 0.0001log-rank p-value for moderate vs. severe 31天0.5 1 2 4 8 16 32HR(95%CI)死亡P值0.0010.0010.0010.120.0010.0010.0010.0010.0010.0010.00131天輸血 0-1天 2-7天 8-30天 31天HR(95%CI)ACUITY研究中，對(duì)于ACS患者遠(yuǎn)期死亡的作用再發(fā)MI：隨時(shí)間而減弱，30天已無(wú)顯著性大出血和輸血：存在持續(xù)影響，1年時(shí)仍具顯著性對(duì)ACS患者遠(yuǎn)期結(jié)局的持

9、續(xù)影響大出血/輸血的影響更甚于缺血Eur Heart J. 2009;30:1457-1466.如何評(píng)估出血風(fēng)險(xiǎn)？出血評(píng)估的有效工具出臺(tái) CRUSADE出血評(píng)分CRUSADE出血評(píng)分計(jì)算器（可從/index.html 獲得）Circulation 2009;119;1873-1882缺血高危因素與出血高危因素大多一致缺血高危因素與出血高危因素大多一致Hector Bueno,Francisco Fernandez-Aviles. Heart 2012;98:162-168ACSACS缺血風(fēng)險(xiǎn)主要預(yù)測(cè)因素缺血風(fēng)險(xiǎn)主要預(yù)測(cè)因素AC

10、SACS出血風(fēng)險(xiǎn)主要預(yù)測(cè)因素出血風(fēng)險(xiǎn)主要預(yù)測(cè)因素老年患者和腎功能不全等特殊人群老年患者和腎功能不全等特殊人群臨床治療尤其應(yīng)重視出血與缺血平衡臨床治療尤其應(yīng)重視出血與缺血平衡抗血小板治療時(shí)，如何減少出血風(fēng)險(xiǎn)？其它抗血小板藥物？(cilostazol, vorapaxar, cangrelor )調(diào)整DAPT持續(xù)時(shí)間？減少APT劑量？圍PCI過程中，何種策略減少出血風(fēng)險(xiǎn)？消化道出血，加用PPI？抗血小板治療時(shí)，如何減少出血風(fēng)險(xiǎn)？其它抗血小板藥物？(cilostazol, vorapaxar, cangrelor )調(diào)整DAPT持續(xù)時(shí)間？減少APT劑量？圍PCI過程中，何種策略減少出血風(fēng)險(xiǎn)？Cilo

11、stazol vs AsaparinCochrane Database Syst Rev. 2011 Jan 19;(1):CD008076.Cochrane Database Syst Rev. 2011 Jan 19;(1):CD008076.CV EVENTS21.Ischaemic strokeCochrane Database Syst Rev. 2011 Jan 19;(1):CD008076.Haemorrhagic strokeCochrane Database Syst Rev. 2011 Jan 19;(1):CD008076.MICochrane Database Sys

12、t Rev. 2011 Jan 19;(1):CD008076.Vascular deathCochrane Database Syst Rev. 2011 Jan 19;(1):CD008076.Extracranial haemorrhageCochrane Database Syst Rev. 2011 Jan 19;(1):CD008076.GI bleedingCochrane Database Syst Rev. 2011 Jan 19;(1):CD008076.Cilostazol+ASA vs ASAAmerican Heart JournalJune 2008Revascul

13、arizatinRestenosisConclusion for cilostazolNO strong evidence for Cilostazol in CHDStronger than ASA, maybe equivalent to TICLIDDecrease bleedingNeed more date to support its use in CHD anti-platelet therapy Vorapaxarprotease-activatedreceptor 1 antagonistTwo large scale RCT results publishedOrigina

14、l 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

15、, 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,

16、 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,

17、 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 InvestigatorsN Engl J MedVolume 366(1):20-33January 5, 201

18、2Study OverviewIn 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 hemorrha

19、ge.Study End Points.Tricoci P et al. N Engl J Med 2012;366:20-33The 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

20、 was a composite of death from cardiovascular causes, myocardial infarction, or stroke. Efficacy End Points.Risk of Bleeding.Tricoci P et al. N Engl J Med 2012;366:20-33Bleeding End Points in the As-Treated Population.Tricoci P et al. N Engl J Med 2012;366:20-33ConclusionsIn patients with acute coro

21、nary 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.background26 449 patients over 3 years prior MI, stroke

22、or peripheral vascular diseaserandomization to vorapaxar or placebo in addition to ASA or ASA+Thienopyridine 2Baseline Characteristics Characterization of Actual Thienopyridine Use From RandomizationCardiovascular death, MI, or stroke stratified by planned thienopyridine useEfficacy end points strat

23、ified by planned thienopyridine useBleeding End Points Stratified by Planned Thienopyridine Use Safety end point stratified by planned thienopyridine useNet Clinical Outcome End Points Stratified by Planned Thienopyridine Use Among Patients With a Previous MI and No History of TIA or Strokeapproved

24、by the FDA and EMA for reducing ischaemic events in patients with a history of MIthe 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 di

25、sease. FDA & EMA recommendationC Vol 382 December 14, 2013 Included studies均聯(lián)合應(yīng)用氯吡格雷均聯(lián)合應(yīng)用氯吡格雷+ASAEfficacy R Vol 382 December 14, 2013 Bleeding E Vol 382 December 14, 2013 Cangrelor reduced the odds of all-cause death, myocardial infarction, or ischaemia-driven revascularisation no difference in the

26、primary safety outcome, in GUSTO moderate bleedingincreased GUSTO mild bleedingConclusion for Cangrelor抗血小板治療時(shí)，如何減少出血風(fēng)險(xiǎn)？其它抗血小板藥物？(cilostazol, vorapaxar, cangrelor )縮短DAPT持續(xù)時(shí)間？減少藥物劑量？圍PCI過程中，何種策略減少出血風(fēng)險(xiǎn)？合并常規(guī)抗凝藥物（房顫），如何處理？3 months出血事件沒有差別！6 monthsCirculation January 24, 20121 year follow-up，no differen

27、ce in bleeding Still no difference in bleeding for 1 year1 monthDuration of DAPT for 1 monthConclusion for shortening DAPT DurationLogically reasonableNo direct evidence yetESC 2015 NSTEACS guidelineEvidence？ Lowering APT dose？50mg vs 75mg clopidogrel50mg vs 75mg clopidogrelBecause of small sample s

28、ize, no difference in bleedingTicagrelor 60mg bid VS 90mg bidPEGASUS Study60mg vs 90mg，略有減少？，略有減少？?jī)H有僅有3年的數(shù)據(jù)結(jié)果，更短時(shí)間是否有差異呢年的數(shù)據(jù)結(jié)果，更短時(shí)間是否有差異呢？Conclusion for lowering doses Lower doses may decrease bleeding Need more data to support the efficacy and safety 抗血小板治療時(shí)，如何減少出血風(fēng)險(xiǎn)？其它抗血小板藥物？調(diào)整DAPT持續(xù)時(shí)間？降低藥物劑量？圍PCI

29、過程中，何種策略減少出血風(fēng)險(xiǎn)？(radial access, bivaludin， fondaparinux)MATRIXCo-primary compositeoutcomes at 30 days N=8404 NSTE-ACS + STEMI Radial vs. femoralValgimigli M et al.Lancet. 2015;385:2465-76All-cause mortality, MI, strokeAll-cause mortality, MI, stroke, or BARC 3 or 5 bleeding75SpeakerRadial vs femoral

30、meta-analysisNon-CABG major bleeedsDeath, MI, or strokeDeathMIStrokePRR (95% CI)Valgimigli M et al.Lancet. 2015;385:2465-76N19 000Radial approach 2015 ESC NSTEACS GuidelineIt is recommended that centres treating ACS patients implement a transition from transfemoral to transradial access.Proficiency

31、in the femoral approach should be maintained (e.g. for IABP insertion and structural as well as peripheral procedures)77Speaker比伐盧定的優(yōu)勢(shì)比伐盧定的優(yōu)勢(shì)u20 個(gè)氨基酸的肽類藥物，凝血酶的直接抑制劑個(gè)氨基酸的肽類藥物，凝血酶的直接抑制劑u與凝血酶的結(jié)合過程可控可逆與凝血酶的結(jié)合過程可控可逆 u血濃度與血濃度與 APTT、PT和和 ACT 正相關(guān)正相關(guān)（ r分別為分別為 0.77、 0.73和和 0.8）u不需要抗凝血酶不需要抗凝血酶（AT-）作為輔助因子，量效關(guān)系更

32、吻合）作為輔助因子，量效關(guān)系更吻合u對(duì)血栓中和循環(huán)中的凝血酶的抑制作用幾乎相同對(duì)血栓中和循環(huán)中的凝血酶的抑制作用幾乎相同u不受激活血小板的影響不受激活血小板的影響u不減少血小板不減少血小板比伐盧定Vs肝素uACUITY試驗(yàn)-JAMA2007uREPLACE-2 試驗(yàn)- TCT 2008uISAR-REACT-4 試驗(yàn)-AHA2011uEUROMAX 試驗(yàn)-NEJM 2013uHORIZONS AMI 試驗(yàn)-NEJM2006，TCT20080.0% -1.6, 1.5 0.76, 1.30-3.3% -5.0, -1.60.60 0.46, 0.77-2.9% -4.9, -0.80.76 0.

33、63, 0.921 endpoint1 endpointMajor 2 endpointStone GW et al. NEJM 2008;358:2218-30HORIZONS AMI 試驗(yàn)試驗(yàn)3,602 發(fā)病發(fā)病 12 小時(shí)的小時(shí)的 STEMI 患者患者 3006 例作支架分組治療，例作支架分組治療，30天臨床結(jié)果天臨床結(jié)果HORIZONS AMI 試驗(yàn)試驗(yàn)3,602 發(fā)病發(fā)病 12 小時(shí)的小時(shí)的 STEMI 患者患者 3006 例作支架分組治療，例作支架分組治療，1年隨訪結(jié)果年隨訪結(jié)果1 年凈臨床不良事件年凈臨床不良事件HORIZONS AMI 試驗(yàn)試驗(yàn)3,602 發(fā)病發(fā)病 12 小時(shí)的

34、小時(shí)的 STEMI 患者患者 3006 例作支架分組治療，例作支架分組治療，1年隨訪結(jié)果年隨訪結(jié)果HORIZONS AMI 試驗(yàn)試驗(yàn)3,602 發(fā)病發(fā)病 12 小時(shí)的小時(shí)的 STEMI 患者患者 3006 例作支架分組治療，例作支架分組治療，3年隨訪結(jié)果年隨訪結(jié)果The Lancet, Volume 377, Issue 9784, 2011, 2193 - 2204Major bleedingCardiac mortalityReinfarctionStent thrombosisAHA 2013 STEMI guideline Bivalirudin seems to be perfect

35、 ! However HEAT-PPCIHEAT-PPCI (Unfractionated Heparin versus Bivalirudin in (Unfractionated Heparin versus Bivalirudin in Primary PCI)Primary PCI)研究研究-開放、單中心、隨機(jī)對(duì)照開放、單中心、隨機(jī)對(duì)照Adeel Shahzad Adeel Shahzad ，ACC 2014u英國(guó)利物浦心胸醫(yī)院，英國(guó)利物浦心胸醫(yī)院，1414名介入醫(yī)生參加，歷時(shí)名介入醫(yī)生參加，歷時(shí)2222個(gè)月個(gè)月u1812 1812 例例STEMISTEMI患者隨機(jī)分組患者隨機(jī)分組u比

36、伐盧定組比伐盧定組905905例患者，例患者，751751例例(83%)(83%)造影后造影后 行介入治療行介入治療；肝素組；肝素組 907 907 例患者，例患者，740740例例 (82%) (82%) 行介入治療行介入治療u兩組兩組 GP IIb/IIIa GP IIb/IIIa 抑制劑應(yīng)用率相似，約抑制劑應(yīng)用率相似，約 13% 13% u3030天臨床終點(diǎn)天臨床終點(diǎn)uLancet. 2014 Jul 4. pii: S0140-6736(14)60924-7.HEAT-PPCI 30天臨床終點(diǎn)OutcomeBivalirudin (%)Heparin (%) RR (95% CI) p

37、MACE2 (1.1 2.1)0.01Definite or probable stent thrombosis1 (1.6 9.5)0.001Major bleeding3.53.1NS對(duì)HEAT-PPCI的批評(píng)u單中心u入選速度（22個(gè)月近2000 例患者）u肝素用量（70U/kg)uACT偏低（H-236，B-270)u入選患者低危u再梗的判斷標(biāo)準(zhǔn)u研究設(shè)計(jì)-知情簽署晚-倫理？u橈動(dòng)脈途徑比例高與出血低有關(guān)NAPLES III 研究u830例高出血風(fēng)險(xiǎn)（危險(xiǎn)積分例高出血風(fēng)險(xiǎn)（危險(xiǎn)積分10）擇期股動(dòng)）擇期股動(dòng)脈途徑脈途徑PCI患者患者u比伐盧定比伐盧定V

38、s UFHu主要終點(diǎn)：院內(nèi)出血主要終點(diǎn)：院內(nèi)出血u主要結(jié)果：按不同出血標(biāo)準(zhǔn)，兩組均無(wú)差異主要結(jié)果：按不同出血標(biāo)準(zhǔn)，兩組均無(wú)差異TCT 2014 BRIGHT研究Stent Thrombosis at 30 DaysEventBivalirudin (n=735), n (%)Heparin (n=729), n (%)Heparin + tirofiban, n (%)pAll definite/probable stent thrombosis4 (0.6)6 (0.9)5 (0.7)0.77Acute (24 h)2 (0.3)2 (0.3)2 (0.3)1.00Subacute (1 3

39、0 d)2 (0.3)4 (0.6)3 (0.4)0.66AHA 2014 NSTE-ACS guideline Recommendations for anticoagulation in NSTE-ACSRecommendationsClassLOEParenteral anticoagulation is recommended at the time of diagnosis according to both ischaemic and bleeding risks.IBFondaparinux (2.5 mg s.c. daily) is recommended as having

40、 the most favourable efficacysafety profile regardless of the management strategy.IBBivalirudin (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.IAUFH 70100 IU/kg i.v. (5070 IU/kg if

41、concomitant with GPIIb/IIIa inhibitors) is recommended in patients undergoing PCI who did not receive any anticoagulant.IBIn 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

42、 recommended during the procedure.IBEnoxaparin (1 mg/kg s.c. twice daily) or UFH are recommended when fondaparinux is not available.IBCrossover between UFH and LMWH is not recommended.IIIBIn NSTEMI patients with no prior stroke/TIA and at high ischaemic risk as well as low bleeding risk receiving as

43、pirin and clopidogrel, low-dose rivaroxaban (2.5 mg twice daily for approximately one year) may be considered after discontinuation of parenteral anticoagulation.IIbBESC 2015 NSTE-ACS guideline 93SpeakerFondaparinux94SpeakerComparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes （NSTEA

44、CS）The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes InvestigatorsN Engl J MedVolume 354;14:1464-1476April 6, 2006Cumulative Risks of Death, Myocardial Infarction, or Refractory Ischemia (Panel A) and of Major Bleeding (Panel B) through Day 9The Fifth Organization to Assess Str

45、ategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476Main Efficacy and Safety OutcomesThe Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476Cumulative Risks of Death (Panel A) and of Death, Myocardial Infarcti

46、on, or Stroke (Panel B) through Day 180The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476Results of Subgroup Analyses of Efficacy (the Composite of Death, Myocardial Infarction, or Refractory Ischemia) (Panel A) and Safety (Major Ble

47、eding) (Panel B) at Nine DaysThe Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476Treatments, Complications, and Outcomes among Patients Undergoing Percutaneous Coronary Intervention (PCI) within the First Eight Days after Randomization

48、The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators N Engl J Med 2006;354:1464-1476Conclusion 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 morbidityRecommendations for anticoagulation in NSTE-ACSRecommendationsClassLOEParenteral anticoagulation is recommended at the time of diagnosis according to both ischaemic and bleeding risks.IBFondaparinux (2.5 mg s.c. daily) is recommended as hav