1 / 50

那些病人能从 GP IIb/IIIa Inhibitors 获益

那些病人能从 GP IIb/IIIa Inhibitors 获益. 中国医学科学院　北京协和医学院 心血管病研究所　阜外心血管病医院 袁晋青. 主要内容. Characteristics of GP IIb/IIIa Inhibitors GP IIb/IIIa Inhibitors in ACS GP IIb/IIIa Inhibitors in STEMI GPIIb/IIIa Inhibitors and PCI. 一、 Characteristics of GP IIb/IIIa Inhibitors. GPIIb/IIIa Inhibitors.

binta
Télécharger la présentation

那些病人能从 GP IIb/IIIa Inhibitors 获益

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 那些病人能从GP IIb/IIIa Inhibitors获益 中国医学科学院　北京协和医学院 心血管病研究所　阜外心血管病医院 袁晋青

  2. 主要内容 • Characteristics of GP IIb/IIIa Inhibitors • GP IIb/IIIa Inhibitors in ACS • GP IIb/IIIa Inhibitors in STEMI • GPIIb/IIIa Inhibitors and PCI

  3. 一、Characteristics of GP IIb/IIIa Inhibitors

  4. GPIIb/IIIa Inhibitors Abciximab Eptifibatide Tirofiban

  5. NH NH H2N O HN–SO2–C4H9 O COOH O OH H N HN O HN N H HN O O O S N O S N H N H H2N O 三种静脉GPⅡb/Ⅲa受体抑制剂的比较 Abciximab Tirofiban Eptifibatide Fab fragment of a chimeric monoclonal antibody MW  50,000 D Nonpeptide tyrosine derivativeMW  500 D Cyclic heptapeptideMW  800 D 合成非肽类 鼠源性单克隆抗体 合成肽类 Topol E, et al. Lancet. 1999;353:227-231.

  6. GP IIb/IIIa 受体拮抗剂作用机制 Plaque rupture and platelet adhesion Platelet activation Prevention of platelet aggregation Resting platelet GP IIb/IIIa expression Fibrinogen Agonists released GP IIb/IIIa inhibitor vWF vWF vWF Vessel Wall White HD. Am J Cardiol. 1997;80(4A):2B-10B.

  7. 三种静脉GPⅡb/Ⅲa受体抑制剂的比较

  8. 二、GP IIb/IIIa Inhibitors in ACS

  9. 20% 20% PRISM-PLUS (n=1,570) PURSUIT (n=9,461) 15.7% 15% 15% Heparin 11.9% 14.2% Heparin 10% 10% Eptifibatide + heparin 8.7% 5% 5% Tirofiban + heparin 0% 0% 0 10 20 30 0 10 20 30 Days Days GP IIb/IIIa Inhibitors in ACS - Death or MI at 30 days - OR 0.70 [0.51, 0.96] P=0.03 OR 0.90 [0.75, 0.98] P=0.04 The Prism-Plus Investigators. NEJM 1998;338:1488-97 The PURSUIT Investigators. NEJM 1998;339:436-43

  10. 42% 23% 31% 6% PCI <72h No early PCI PCI <72h No early PCI (n=287) (n=1283) (n=1228) (n=8233) Impact of Early PCI on 30 Day Death/MI PRISM Plus PURSUIT Heparin Tirofiban + Heparin Heparin Eptifibatide+Heparin 15% 20% 16.7% 15.6% 14.5% 10.2% 15% 10.1% 10% 11.6% 7.8% 10% 5.9% 5% 5% 0% 0%

  11. GPIIb/IIIa Inhibitors in ACS 30-Day mortality results of a Meta-analysis* 10% GPIIb/IIIa Inhibitor Placebo P=0.007 6.2% P=NS 5% 4.6% 3.0% 3.0% n= 6,458 n= 23,072 Non-DM DM * PRISM, PRISM-PLUS, PARAGON A & B, PURSUIT, GUSTO-IV Circulation 2001;104:2767-71

  12. GPIIb/IIIa Inhibitors in Diabetic Patients with ACS 30-Day Mortalityof a Meta-analysis* 10% GPIIb/IIIa Inhibitor Placebo P=0.1 6.7% P=0.002 5.5% 5% 4.0% 1.2% n= 5,179 n= 1,279 No PCI PCI * PRISM, PRISM-PLUS, PARAGON A & B, PURSUIT, GUSTO-IV Circulation 2001;104:2767-2771

  13. GUSTO-IV Study Design Non ST-segment elevation ACS Medical rx only planned (no angio or PCI) (n=7800) 2598 ASA+UFH or LMUH +placebo 2590 ASA+UFH + Abciximab 24h 2612 ASA+UFH + Abciximab 48h 2598 2590 2612 Lancet 2001; 357: 1915-24

  14. GUSTO-IV30-Day outcomes 9.1% 10% 8.2% 8.0% 8% 5.9% 5.6% 5.1% 6% 4.3% 3.9% 3.4% 4% 2% P = 0.235 P = 0.190 P = 0.664 0% Death, MI Death MI placebo Abciximab 24h Abciximab 48h Lancet 2001; 357: 1915-24

  15. GUSTO-IVsafety outcomes * p < 0.05,vs placebo * * * * * < 50,000 per µL < 100,000 per µL Lancet 2001; 357: 1915-24

  16. Benefits of GP IIb/IIIa Inhibitors by Troponin Status in Clinical Trials TnT-Positive TnT-Negative PARAGON-B PRISM CAPTURE Combined 0.125 0.5 1 2 0.125 0.5 1 2 GP IIb/IIIa Better GP IIb/IIIa Worse GP IIb/IIIa Better GP IIb/IIIa Worse Circulation 2001;103:2891-96

  17. 20 15 10 5 0 ISAR-REACT 2 Death, MI, or urgent TVR in Subsets With and Without Elevated Troponin Levels (>0.03 µg/L) Placebo Group (N=1010) Abciximab Group (N=1012) % Troponin >0.03 µg/L Log-Rank p = 0.02 Troponin <0.03 µg/L Log-Rank p = 0.98 0 5 10 15 20 25 30 Days After Randomization JAMA 2006; 295:1531-38

  18. 早期应用有效降低住院死亡率NRMI注册研究 N=60770 NSTEMI患者 住 院 死 亡 率 % NRMI-NSTEMI Risk Score NRMI=National Registry of Myocardial Infarction. Peterson E, et al. J Am Coll Cardiol. 2003;42:45-53

  19. (n=2522) (n=2041) (n=3803) (n=1105) 3.0  2.8% 2.3% 2.5 2.0 1.7% 1.5 1.0 0.5 0% 0.0 <6 hours 6–12 hours 12–24 hours >24 hours 越早用药 绝对获益越大 PURSUIT研究： GPIIb/IIIa VS 安慰剂 30天死亡 /心梗绝对下降(%) 1.7%  2.3%  用 药 距 离 发 病 的 时 间 JAMA. 2000; 284:1549-1558

  20. I IIa IIb III UA/NSTEMI行PCI的患者，如未服用氯吡格雷，应给予一种血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂，在实施诊断性CAG前或PCI术前即刻给药均可 UA/NSTEMI行PCI的患者，如已服用氯吡格雷，可同时给予一种血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂 STEMI行PCI的患者，可尽早应用血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂 接受择期PCI并置入支架的高危患者或高危病变（如ACS、近期MI、桥血管狭窄、冠状动脉慢性闭塞病变及CAG可见的血栓病变等），可应用血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂，但应充分权衡出血与获益风险 A B B B 2009年中国PCI治疗指南 GPⅡb/Ⅲa受体拮抗剂推荐

  21. 三、 GP IIb/IIIa Inhibitors in STEMI

  22. GP IIb/IIIa Inhibitors in STEMI Abciximab and PCI in STEMI Trials 30 Day Endpoint (D, Re-MI, u-TVR) % p<0.05 p=0.005 p=0.038 p=0.023 p=0.01 PTCA N = 483 Stent N = 401 Stent N = 301 PTCA or Stent N = 2082 Stent N = 400

  23. RAPPORTAbciximab in primary PTCA for STEMI 7-day Outcome P=0.003 9.9% p=0.098 P=0.01 5.0% 5.4% 3.3% 2.1% 1.2% Circulation 1998;98;734-741

  24. RAPPORT 30 – Day follow-up P=0.03 11.2% P=0.006 P=0.52 6.6% 5.8% 5.8% 4.6% 1.7% Circulation. 1998; 98: 734-741

  25. RAPPORT6 month follow-up P=0.9 28.1% 28.2% P=0.048 17.8% P=0.36 11.6% 11.2% 8.7% Circulation. 1998; 98: 734-741

  26. CADILLAC AMI <12 h, cardiogenic shock excluded N = 2082 76 centers in N.A. S.A. and Europe randomization Primary PTCA (n=518) MultiLink stent + Abciximab (n=524) Primary PTCA + Abciximab (n=528) MultiLink stent (n=512) N Engl J Med 2002; 346: 957-966

  27. CADILLAC Kaplan-Meier Estimates of the Clinical Outcomes at 30 Days and 6 Months N Engl J Med 2002; 346: 957-966

  28. CADILLAC30 day acute thrombosis P=0.05 P=0.03 N Engl J Med 2002; 346: 957-966

  29. CADILLAC thrombocytopenia and bleeding evnts PTCA PTCA/Abcx Stent Stent/Abcx p Bleeding - sever 0.6% 0.2% 0.4% 0.8% 0.58 - moderate 2.5% 2.3% 4.3% 2.5% 0.18 - intrcranial 0% 0% 0% 0.2% 0.99 thrombocytopenia 1.4% 4.0% 2.6% 4.0% 0.02 Blood-product intrafusion 3.7% 5.1% 4.1% 5.0% 0.62 N Engl J Med 2002; 346: 957-966

  30. 在救护车或急诊室开始用药 在导管室或CCU开始用药 ADMIRAL研究 300 患者， AMI <12 小时 在急诊支架置入前，随机接受阿昔单抗，并与安慰剂比较 P=NS P=NS P<0.05 P<0.05 Circulation 2001; 103:2328-2335

  31. PRISM-PLUS Angiographic Substudy: Tirofiban Increased Perfusion Status P=0.002 for trend by proportional odds model Zhao X-Q, et al. Circulation. 1999;100:1609-1615.

  32. GPIIb/IIIa受体拮抗剂治疗建议 • 中高危NSTE-ACS患者(尤其TnT↑、ST↓或糖尿病)，可在氯吡格雷+ ASA基础上，加用GPIIb/IIIa拮抗剂 • 不建议STEMI患者溶栓时联合应用GPIIb/IIIa受体拮抗剂，尤其是年龄大于75岁的患者 • GPIIb/IIIa拮抗剂应在抗凝治疗基础上应用(UFH或LMWH) • 出血危险较高患者慎用或禁忌；若应用GPIIb/IIIa受体拮抗剂，应监测血红蛋白和血小板计数

  33. I IIa IIb III UA/NSTEMI行PCI的患者，如未服用氯吡格雷，应给予一种血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂，在实施诊断性CAG前或PCI术前即刻给药均可 UA/NSTEMI行PCI的患者，如已服用氯吡格雷，可同时给予一种血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂 STEMI行PCI的患者，可尽早应用血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂 接受择期PCI并置入支架的高危患者或高危病变（如ACS、近期MI、桥血管狭窄、冠状动脉慢性闭塞病变及CAG可见的血栓病变等），可应用血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂，但应充分权衡出血与获益风险 A B B B 2009年中国PCI治疗指南 GPⅡb/Ⅲa受体拮抗剂推荐

  34. 四、 GPIIb/IIIa Inhibitors and PCI

  35. GPIIb/IIIa Inhibitors and PCImeta-Analysis 0.62 (0.55, 0.71) p < 0.000000001 16,770 8.8% 5.6% 0 0.5 1 1.5 2 30-day MI/death GPI better Placebo better

  36. EPISTENT1-year results in diabetes † P<0.546 * P<0.035 † P<0.290 † P<0.389 * P<0.005 * P<0.022 † P<0.440 * P<0.11 †stent+placebo VS angiolpasy+abciximab * stent+placebo VS stent+abciximab Lancet 1999; 354: 2019-24

  37. EPISTENT 1-year mortality 2.4% stent+placebo stent+Abciximab 2.1% angioplasty+Abciximab 1.0% p = 0.037 (days) 0 30 60 90 120 150 180 210 240 270 300 330 360 Follow-up Lancet 1999; 354: 2019-24

  38. EPISTENT1-year results in non-diabetes † P<0.014 * P<0.369 † P<0.084 † P<0.062 * P<0.001 * P<0.002 † P<0.852 * P<0.156 †stent+placebo VS angiolpasy+abciximab * stent+placebo VS stent+abciximab Lancet 1999; 354: 2019-24

  39. TARGETTirofiban vs Abciximab in PCI30-day results 1.26 1.21 2.80 1.27 1.26 1.26 2.43 0.0 0.5 1.0 1.5 2.0 Tirofiban better Abciximab better N Engl J Med 2001; 344: 1888-94

  40. TARGETTirofiban vs Abciximab in PCI 6-month follow-up N Engl J Med 2001; 344: 1888-94

  41. ISAR-REACT abciximab in elective PCI exclude recent MI, ACS, diabetes % abciximab 5 placebo ALL= NS 4 3.3 3.3 3 2 0.9 0.7 1 0.5 0.4 0.3 0.3 0 Death Q-MI NQ-MI Urgent TVR J Am Coll Cardiol 2004; 44: 2133-36

  42. ISAR-REACT abciximab in elective PCIsafety outcomes % abciximab placebo 5 P=0.37 P=0.38 P=0.002 P=0.007 4 2.5 3 2.4 1.9 2 1.1 0.9 0.9 0.7 1 0 0 thrombocytopenia major bleeding minor bleeding transfusion J Am Coll Cardiol 2004; 44: 2133-36

  43. ESPRIT ASA, clopidogrel, randomization in cath lab Eptifibatide 180+180 μg/kg bolus (boluses 10 min apart) 2.0 μg/kg-min infusion×18-24o + Heparin 60 U/mg bolus (ACT 200-300sec) Placebo+ Heparin 60U/kg bolus (ACT 200-300 sec) VS. Elective PCI 48 hour, 30day, 6 month, 1 year follow-up Lancet 2000; 356: 2037- 44

  44. ESPRITeptifibatide in elective PCI30-Day results Placebo Eptifibatide 12% 10% 10.2% 8% 6% Death or MI (%) 6.4% P = 0.0014 4% RR = 0.62 2% 0% 30 20 10 Days following randomization Lancet 2000; 356: 2037-44

  45. ESPRIT30-Day Stroke and bleeding * * * p<0.03 * * Major bleeding (TIMI) Lancet 2000; 356: 2037-44

  46. Abciximab in PCI: Complex Lesions EPIC and EPILOG : 30 day Events (D, MI, uTVR) % p=.047 p=.001 p=.001 p=.001 p=.078 p=.001 p=.001 p=.001 p=.001 JACC 1998; 32:1619-23

  47. EPISTENTAbciximab for Complex Lesions 30 day D, MI, uTVR % p=0.17 p<0.001 Lancet 1999; 354: 2019-24

  48. I IIa IIb III UA/NSTEMI行PCI的患者，如未服用氯吡格雷，应给予一种血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂，在实施诊断性CAG前或PCI术前即刻给药均可 UA/NSTEMI行PCI的患者，如已服用氯吡格雷，可同时给予一种血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂 STEMI行PCI的患者，可尽早应用血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂 接受择期PCI并置入支架的高危患者或高危病变（如ACS、近期MI、桥血管狭窄、冠状动脉慢性闭塞病变及CAG可见的血栓病变等），可应用血小板糖蛋白Ⅱb/Ⅲa受体拮抗剂，但应充分权衡出血与获益风险 A B B B 2009年中国PCI治疗指南 GPⅡb/Ⅲa受体拮抗剂推荐

  49. 小 结 • 血小板在ACS发病中起重要作用 • 抗血小板治疗是ACS的关键治疗之一 • GPⅡb/Ⅲa拮抗剂尤其适宜于中高危行介入治疗的ACS患者 • 三重抗血小板治疗在ACS伴TNI升高者中尤为重要

  50. 谢 谢！

More Related