ST抬高心肌梗死溶栓與抗栓治療進(jìn)展.ppt

ST抬高心肌梗死溶栓與抗栓治療 -2009進(jìn)展,西安交通大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院 心內(nèi)科 袁祖貽,急性ST段抬高心梗治療目標(biāo),恢復(fù)心肌水平再灌注 盡早、完全、持續(xù),降低死亡率改善預(yù)后,Yusuf S, et al. Circulation. 1990;82(suppl II):II-117-II-134. Schrder R, et al. J Am Coll Cardiol. 1995;26:1657-1664.,時(shí)間就是心??！ 時(shí)間就是生命！,Symptom Recognition,Call to Medical System,ED,Cath Lab,PreHospital,Delay in Initiation of Reperfusion Therapy,Increasing Loss of Myocytes,Treatment Delayed is Treatment Denied,溶栓治療 ？ 直接 PCI ？,STEMI病人，應(yīng)采取何種再灌注策略：,溶栓 vs 直接 PCI,溶栓 血流TIMI 3 比例60% 再梗死發(fā)生率 4% 卒中總發(fā)生率 2% ICH發(fā)生率 1% 任何地點(diǎn)(院前) 任何時(shí)間 所有醫(yī)生 無時(shí)間延遲 大規(guī)模臨床試驗(yàn)證實(shí),直接PCI 血流TIMI 3 比例80-90% 再梗死發(fā)生率 1h),評估STEMI再灌注方式 ACC/AHA 2007 STEMI Guidelines,癥狀發(fā)作后的時(shí)間 STEMI危險(xiǎn)分層 溶栓風(fēng)險(xiǎn) 轉(zhuǎn)運(yùn)至熟練PCI導(dǎo)管室所需時(shí)間,Circulation 2007 August 10;114:671-719,步驟1：評估時(shí)間和危險(xiǎn)性,評估STEMI再灌注方式 ACC/AHA 2007 STEMI Guidelines,步驟2：決定應(yīng)首選溶栓還是PCI 如果時(shí)間少于3小時(shí)，且介入治療無耽擱，溶栓和PCI首選哪種都可以，二者在減少梗死面積，降低死亡率方面效果相似。但傾向PCI，因可降低出血與卒中。,Circulation 2007 August 10;114:671-719,312小時(shí)患者， PCI可挽救更多心肌，還可減少卒中。 如無PCI條件，且有溶栓禁忌，應(yīng)立即轉(zhuǎn)院。 23個(gè)隨機(jī)研究，直接PCI降低全因死亡，非致死MI，卒中，通暢率，心功能等指標(biāo)優(yōu)于靜脈溶栓。,Circulation 2007 August 10;114:671-719,直接PCI與溶栓療法的匯萃分析 （23個(gè)隨機(jī)研究）,PCI,Lytics,7%,7%,5%,9%,總死亡 (包括心源性休克),1%,P=0.0002,P=0.0003,(n = 7739),(%) Events,死亡 (排除心源性休克),非致命性 再次心梗,中風(fēng),Hemorrhagic CVA,0.05%,2%,1%,7%,3%,P0.0001,P0.0001,P0.0001,Keeley et al， Lancet 2003; 361:13-20,ACC/AHA 2007 & ESC 2008 指南: 直接PCI 應(yīng)用于急性ST段抬高心梗,Class I 一般考慮 發(fā)病 12 小時(shí)之內(nèi) 患者就診到球囊開通血管時(shí)間 75 例 / 年 導(dǎo)管室手術(shù)量 200 例 / 年，直接PCI 36 例 / 年 有胸外科支持,Circulation 2007 August 10;114:671-719,Class I 癥狀發(fā)作時(shí)間 1小時(shí), 溶栓療法更好 癥狀發(fā)作時(shí)間 3小時(shí)，直接 PCI 更好,Circulation 2007 August 10;114:671-719,STEMI ：直接 PCI 治療,四個(gè)高危亞組直接PCI療效優(yōu)于溶栓組 心源性休克 前壁心梗、再發(fā)心梗 心力衰竭 老年人 70 歲,溶栓治療是否已經(jīng)過時(shí)？,各種原因?qū)е碌臅r(shí)間延遲大大降低了直接PCI的獲益。對于不能直接PCI達(dá)到理想再灌注的患者，溶栓治療仍然是較好的選擇！ 即使在歐美國家，AMI再灌注治療中溶栓與直接PCI的比例相當(dāng)。國際上多項(xiàng)注冊研究顯示，雖然PCI治療近年來增長迅速，但仍有接近40%的患者接受溶栓治療。,急性ST段抬高心肌梗死溶栓治療的中國專家共識(shí)(2009年更新版).,“時(shí)間就是心肌” - 時(shí)間與死亡率關(guān)系（NRMI-2 研究）,P=0.01,P=0.0007,P=0.0003,NRMI 2: Primary PCI door-to- balloon time vs mortality,n = 2,230,5,734,Door-to-balloon time (minutes),6,616,4,461,2,627,5,412,0-60 61-90 91-120 121-150 150-180 180,Mortality(%),不具備24h急診PCI治療條件的醫(yī)院。 不具備24h急診PCI治療條件也不具備迅速轉(zhuǎn)運(yùn)條件的醫(yī)院。 具備24h急診PCI治療條件，患者就診早（癥狀持續(xù)3h）； 具備24h急診PCI治療條件，患者就診時(shí)癥狀持續(xù)大于3小時(shí)，但就診-球囊擴(kuò)張與就診-溶栓時(shí)間相差（PCI相關(guān)的延誤）超過60min或就診-球囊擴(kuò)張時(shí)間超過90min（新指南的建議為：FMC（首次醫(yī)療接觸）到球囊擴(kuò)張的時(shí)間）。,時(shí)間就是心??！,溶栓治療首選條件(2009),2009急性ST段抬高心梗溶栓治療中國專家共識(shí),再次溶栓治療,如果患者有證據(jù)顯示血管持續(xù)閉塞、開通后在閉塞或下降的ST段再次抬高?；颊邞?yīng)該立即進(jìn)行PCI或轉(zhuǎn)運(yùn)至可行PCI的醫(yī)院，此外，可考慮進(jìn)行再次溶栓治療，并選擇無免疫原性的溶栓藥物。,溶栓藥物的選擇,非特異性纖溶酶原激活劑- 鏈激酶(SK) 和尿激酶（UK） 特異性纖溶酶原激活劑- 人重組組織型纖溶酶原激活劑（rt-PA） 瑞替普酶(r-PA)，蘭替普酶(n-PA)，替耐普酶 (TNK-tPA),不同溶栓藥物主要特點(diǎn)的比較, 2009急性ST段抬高心梗溶栓治療的中國專家共識(shí),我國溶栓治療的患者中絕大多數(shù)（90%）應(yīng)用非選擇性溶栓藥物, 應(yīng)用組織型纖溶酶原激活劑（t-PA）者僅占2.7%。 應(yīng)該積極推進(jìn)規(guī)范的溶栓治療，以提高我國急性急性ST段抬高心梗的再灌注治療的比例和成功率！,急性ST段抬高心肌梗死溶栓治療的中國專家共識(shí)(2009年更新版).,首診到基層醫(yī)院的AMI病人，應(yīng)采取何種再灌注策略： 就地溶栓治療 ？ 轉(zhuǎn)運(yùn)直接 PCI ？,PRAGUE 研究,p = ns,p 0.02,Widimsky et al Eur Heart J 2003; 24: 94,轉(zhuǎn)運(yùn)PCI 和就地溶栓治療對死亡率的影響（發(fā)病時(shí)間考慮）,STEMI：轉(zhuǎn)院距離短，延遲時(shí)間不長（PCI90min）,PRAGUE-2 Study (N=300),p0.001,23.0%,15.0%,8.0%,p0.001,ESC 2007, Sept 1-4,STEMI：擬轉(zhuǎn)院PCI，但延遲時(shí)間較長(PCI90min) ,直接PCI？ 易化PCI？,ASSENT-4研究,2006年發(fā)表在Lancet； 1120例患者比較：直接PCI vs 易化PCI； 易化PCI組死亡率顯著增高； 只有低出血/高危STEMI患者獲益。,FINESSE研究,2007年ESC會(huì)議上公布； 2453例STEMI：瑞替普酶+阿昔單抗易化PCI vs 阿昔單抗易化PCI vs 直接PCI 雖然易化PCI組術(shù)前冠脈血流明顯優(yōu)于直接PCI組，但三組90天死亡、心衰、心源性休克等MACE發(fā)生率無差異； 易化PCI組出血危險(xiǎn)明顯增高。,ESC 2007, Sept 1-4,AHA/ACC 2007 & ESC 2008 Guideline：異化PCI,低出血風(fēng)險(xiǎn)的高危STEMI患者，在不能立即行PCI時(shí)可采用異化PCI策略。（Class b）,2009年：CAPTIM最新隨訪結(jié)果,Bonnefoy E et al, European Heart Journal 2009.,急性ST段抬高心?；颊?直接行PCI (n=421),rt-PA異化PCI (n=419),CAPTIM:異化PCI降低5年全因死亡率,患者癥狀發(fā)作6小時(shí)內(nèi)，rt-PA溶栓后行PCI的5年全因死亡率為 9.7% vs 12.6%,Bonnefoy E et al, European Heart Journal 2009.,癥狀發(fā)作2小時(shí)內(nèi)，p=0.04 HR 0.50(95% CI,0.25-0.97),癥狀發(fā)作2小時(shí)內(nèi)，rt-PA溶栓后行PCI的5年死亡率僅為單純PCI組的50%,Bonnefoy E et al, European Heart Journal 2009.,死亡風(fēng)險(xiǎn) 50%,CAPTIM:異化PCI降低5年全因死亡率,2009ESC：NORDISTEMI,Objective: To compare 2 different strategies after thrombolysis for STEMI in patients with very long transfer times: A: Immediate transfer for CAG/PCI B: Conservative, ischemia-guided treatment,Halvorsen S: Presented in ESC 2009,NORDISTEMI：study design,Bonnefoy E et al, European Heart Journal 2009.,Acute STEMI 90 min,Clinical Outcome at 30 days:,Conservative,Invasive,21%,4.5%,9.8%,10%,Death,re-MI,stroke New ischemia,RR=0.49(0.27-0.89) P=0.003,(%) Events,Death,re-MI,stroke),Death,2.2%,2.3%,Bonnefoy E et al, European Heart Journal 2009.,RR=0.45(0.16-1.14) P=0.14,STEMI藥物再灌注治療組成要素,Fibrinolytic SK Fibrin- specific,Antiplatelet ASA GP IIb/IIIa Clopidegrel,Anticoagulant UFH Alternative Agents,STEMI長期雙重抗血小板治療明顯獲益,CLARITY TIMI-28,COMMIT/CCS-2,ESC 2008: STEMI Guideline,糖蛋白b/a抑制劑：,糖蛋白b/a抑制劑與溶栓藥物聯(lián)合可提高療效，但出血并發(fā)癥增加。 阿昔單抗和半量瑞替普酶或替奈普酶聯(lián)合使用進(jìn)行再灌注治療對前壁心肌梗死、年齡75歲，沒有出血危險(xiǎn)因素的患者可能有益，可預(yù)防再梗死以及STEMI的并發(fā)癥。 但是臨床研究顯示，糖蛋白b/a抑制劑與溶栓聯(lián)合沒有降低病死率，尤其對75歲以上的患者，因?yàn)槌鲅L(fēng)險(xiǎn)明顯增加， 不建議藥物溶栓與糖蛋白b/a 抑制劑聯(lián)合。,ESC 2008: STEMI Guideline 2009STEMI溶栓治療的中國專家共識(shí),依諾肝素顯著降低主要終點(diǎn)事件（死亡或非致命性心梗）相對風(fēng)險(xiǎn)17(ExTRACT-TIMI 25),相對風(fēng)險(xiǎn): 0.83 (0.770.90) p0.0001,依諾肝素,普通肝素,0,5,10,15,20,25,30,天,0,3,6,9,12,15,主要終點(diǎn)事件 (%),相對風(fēng)險(xiǎn): 0.90 (0.801.01) p=0.08,相對風(fēng)險(xiǎn): 0.77 (0.71 0.85) p0.0001,48 h,8 days,9.9%,12.0%,4.7%,5.2%,7.2%,9.3%,RRR17%,2,8,(2006年3月ACC 上首次公布的對所有患者的分析結(jié)果),Thank you for your attention!,Thrombolysis and antithrombolism for STEMI-Advancement in 2009,Zuyi Yuan Dept of Cardiovascular Medicine, First Affiliated Hospital of Medical School, Xian Jiaotong University,Goals for AMI Therapy,Restore coronary blood flow to ischemic myocardium Rapidly, Completely and sustain,Reducing the mortality AMI survivor with an improved outcome,Yusuf S, et al. Circulation. 1990;82(suppl II):II-117-II-134. Schrder R, et al. J Am Coll Cardiol. 1995;26:1657-1664.,Time is the Myocardium！ Time is the life！,Symptom Recognition,Call to Medical System,ED,Cath Lab,PreHospital,Delay in Initiation of Reperfusion Therapy,Increasing Loss of Myocytes,Treatment Delayed is Treatment Denied,Thrombolysis ？ Primary PCI ？,STEMI: the choice of strategies for reperfusion,Thrombolysis vs Primary PCI,Thrombolysis TIMI 3 flow: 60% Re-MI rate: 4% Stroke rate: 2% ICH rate: 1% Anywhere (pre-hospital) anytime All doctor No time delay RCT documented,Primary PCI TIMI 3 flow: 80-90% Re-MI rate: 1h),Strategies for STEMI: ACC/AHA 2007 & ESC 2008 STEMI Guidelines,the time of onset present STEMI risk score risk of thrombolysis the time for transfer to PCI cathlab,Circulation 2007 August 10;114:671-719,Step 1：Evaluating the time and risk,Step 2：The choice of thrombolysis or PCI? If the time of onset is 3 hours, and no invasive delay, no difference in thrombolysis and PCI; the two strategies are similar in reducing the area of infarction and reducing mortality. But prefer to PCI, since to reducing bleeding and stroke.,Circulation 2007 August 10;114:671-719,Strategies for STEMI: ACC/AHA 2007 & ESC 2008 STEMI Guidelines,Onset in 312 hours, PCI is the better, because of salvaging more ischemic myocardium, and reducing the stroke. If no PCI qualification, and have the counterconditions，the patient should be transfer immediately. 23 RCT have documented, primary PCI reduce the mortality, re-MI, stroke, and preserved the heart function is better vs thrombolysis.,Circulation 2007 August 10;114:671-719,Primary PCI vs Thrombolysis: Meta-analysis（23 RCT）,PCI,Lytics,7%,7%,5%,9%,Total mortality,1%,P=0.0002,P=0.0003,(n = 7739),(%) Events,mortality,Re-MI,stroke,Hemorrhagic CVA,0.05%,2%,1%,7%,3%,P0.0001,P0.0001,P0.0001,Keeley et al， Lancet 2003; 361:13-20,ACC/AHA 2007 & ESC 2008 Guigeline: Primary PCI in STEMI:,Class I In general Onset 75 case / year Cathlab PCI case 200 case / year, Primary PCI 36 case / year Surgical standby,Circulation 2007 August 10;114:671-719,Class I if onset 1 hour, thrombolysis is better if onset 3 hours，primary PCI is better,Circulation 2007 August 10;114:671-719,STEMI ：Primary PCI,Four high risk score subgroup the PCI is better vs thrombolysis Cardiac shock Anterioreor M, re-MI Heart failure age 70 years,Thrombolytic therapy is behind the times？,Different causes result in PCI time delay limited the primary PCI benefice. For nor primary PCI usable patients, thrombolysis is still the best chioce！ Although in western，AMI reperfusion therapy is still important. International register study showed: 40% AMI were performed thrombolysis.,急性ST段抬高心肌梗死溶栓治療的中國專家共識(shí)(2009年更新版).,“Time is the myocardium” the ralationship of Time and Mortality（NRMI-2 study）,P=0.01,P=0.0007,P=0.0003,NRMI 2: Primary PCI door-to- balloon time vs mortality,n = 2,230,5,734,Door-to-balloon time (minutes),6,616,4,461,2,627,5,412,0-60 61-90 91-120 121-150 150-180 180,Mortality(%),For hospital: No 24h primary PCI cathlab usable。 For hospital: No 24h primary PCI cathlab usable, and meantime, thansfer is delay. For hospital: 24h primary PCI cathlab usable，onset 3 hours；D-B time D-N time 60min。,Time is the myocardium！,First Chioce for Thrombolysis (2009),2009急性ST段抬高心梗溶栓治療中國專家共識(shí),Re-thrombolytic therapy:,If have evidence showed the failure of reperfusion and re-MI, patient should be transfer to perform PCI immediately, otherwise patient should be perform re-thrombolytic therapy.,The Chioce of Thrombolytic Drugs,非特異性纖溶酶原激活劑- 鏈激酶(SK) 和尿激酶（UK） 特異性纖溶酶原激活劑- 人重組組織型纖溶酶原激活劑（rt-PA） 瑞替普酶(r-PA)，蘭替普酶(n-PA)，替耐普酶 (TNK-tPA),The characteristic comparion of difference thrombolytic drugs, 2009急性ST段抬高心梗溶栓治療的中國專家共識(shí),我國溶栓治療的患者中絕大多數(shù)（90%）應(yīng)用非選擇性溶栓藥物, 應(yīng)用組織型纖溶酶原激活劑（t-PA）者僅占2.7%。 應(yīng)該積極推進(jìn)規(guī)范的溶栓治療，以提高我國急性急性ST段抬高心梗的再灌注治療的比例和成功率！,急性ST段抬高心肌梗死溶栓治療的中國專家共識(shí)(2009年更新版).,For AMI patient, the first contact in raral hospital，which strategies for reperfusion： Thrombolysis ？ Transfer to PCI ？,PRAGUE study,p = ns,p 0.02,Widimsky et al Eur Heart J 2003; 24: 94,Transfer PCI vs Thrombolysis （onset time concise）,STEMI：short transfer distant，no cathlab delay（PCI90min）,PRAGUE-2 Study (N=300),p0.001,23.0%,15.0%,8.0%,p0.001,ESC 2007, Sept 1-4,STEMI：is plan to PCI，but cathlab delay (PCI90min) ,Primary PCI？ After thrombolytic PCI (TT-PCI)？,ASSENT-4 study,2006 published in Lancet； 1120 case：Primary PCI vs TT-PCI； The mortality is significant higher in TT-PCI group； Only the low bleeding/high risk STEMI subgroup is beneficial。,FINESSE study,First presented in ESC 2007； 2453 case STEMI：rt-PA+GPI PCI vs GPI PCI vs Primary PCI Although the cronary flow is better in TT-PCI compare the preimary PCI, but the three groups have not difference in death, HF, cardiac shock (MACE) ； The risk for bleeding is high in TT-PCI group .,ESC 2007, Sept 1-4,AHA/ACC 2007 & ESC 2008 Guideline： for TT-PCI,Low bleeding risk and high risk score STEMI patient，TT-PCI perform in no cathlab usable。（Class b）,2009：CAPTIM new F-U data,Bonnefoy E et al, European Heart Journal 2009.,CAPTIM:TT-PCI reduce the 5-year mortality,Bonnefoy E et al, European Heart Journal 2009.,Onset 2hours，p=0.04 HR 0.50(95% CI,0.25-0.97),Bonnefoy E et al, European Heart Journal 2009.,RR 50%,CAPTIM:TT-PCI reduce the 5-year mortality,2009ESC：NORDISTEMI,Objective: To compare 2 different strategies after thrombolysis for STEMI in patients with very long transfer times: A: Immediate transfer for CAG/PCI B: Conservative, ischemia-guided treatment,Halvorsen S: Presented in ESC 2009,NORDISTEMI：study de