GP IIbIIIa抑制剂在PCI中的应用课件.ppt

GP IIb/IIIa Inhibitors in the PCI Setting Objectives• Discuss the pivotal role of platelets in the development of ischemic complications after percutaneous coronary intervention (PCI), including high-risk populations such as patients with diabetes • Explore the optimization of PCI outcomes through adequate platelet inhibition achieved through early initiation or in-lab administrationObjectives (continued)• Address the need to consider and study a more aggressive dosing schedule for reversible glycoprotein (GP) IIb/IIIa inhibitors • Discuss the significance of the upcoming, large -scale TENACITY trial, which will test current and emerging clinical practice around combination therapy using GP IIb/IIIa platelet inhibitors • Review the safety profile of therapies for PCIGP IIb/IIIa Inhibitors in the PCI Setting Module 1: Early Utilization of GP IIb/IIIa Inhibitors in High-Risk PopulationsACS=acute coronary syndrome. UA=unstable angina. Bhatt DL. J Invasive Cardiol. 2003;15:3B-9B.Acute Plaque Rupture(UA/NSTEMI/STEMI)Presence of Multiple Coronary PlaquesPersistent Hyperreactive PlateletsVascular InflammationClinicalSubclinicalACS: The Tip of the Atherothrombotic “Iceberg”NSTEMI=non-ST-segment elevation myocardial infarction. STEMI=ST-segment elevation myocardial infarction.American Heart Association. 2002 Heart and Stroke Statistical Update. 2001.•Single largest cause of death—529,659 deaths in the U.S. in 1999—1 in every 5 deaths •Incidence—1,100,000 Americans will have a new or recurrent coronary attack each year and about 45% will die*—550,000 new cases of angina per year •Prevalence—12,900,000 with a history of myocardial infarction (MI), angina, or both*Based on data from the Atherosclerotic Risk in Communities (ARIC) study of the National Heart, Lung, and Blood Institute, 1987–94. Includes Americans hospitalized with definite or probable MI or fatal coronary heart disease (CHD), not including silent MIs.ACS in the United States Hospital Admissions for ACS: UA/NSTEMI* versus STEMI†ACS2.3 million hospital admissions ACSUA/NSTEMIUA/NSTEMI1.43 million admissions per year*Also known as non-Q-wave MI. †Also known as Q-wave MI.National Center for Health Statistics. 2001.STEMISTEMI829,000 admissions per yearSTEMIClinical findingEKGSerum markersRisk assessmentNon-cardiac chest painStable anginaUANSTEMINegativePositiveST-T wave changesST elevationLow probabilityMedium-high riskThrombolysis Primary PCIAspirin + GP IIb/IIIa inhibitor clopidogrel + heparin/ LMWH + anti-ischemic Rx Early invasive RxDischargeNegativeDiagnostic rule out MI/ACS pathwaySTEMINegativeAtypical painLow riskAspirin, heparin/low-molecular- weight heparin (LMWH) + clopidogrel Anti-ischemic Rx Early conservative therapyOngoing painDM=diabetes mellitus. Cannon, Braunwald. Heart Disease. 2001.Rest pain, Post-MI, DM, Prior AspirinExertional painThe Spectrum of ACSLMWH: Potential Advantages• Increased anti-Xa to anti-IIa activity  inhibits thrombin generation more effectively—Dalteparin 2:1, enoxaparin 3.8:1 • Less binding to plasma proteins (eg, acute-phase reactant proteins)  more consistent anticoagulation • Lower rate of thrombocytopenia vs unfractionated heparin (UFH) • Subcutaneous administration, dosing twice daily • No need to monitor its effectsOR and 95% CI Eikelboom J, et al. Lancet. 2000;355:1936-1942.0.1 1.0 10.0Favors HeparinFavors ControlControl %UFH or LMWH %03.1Cohen4.5Grand total7.40.53 (0.38 - 0.73)7.910.4UFH vs placebo0.67 (0.45 - 0.99)5.74.8FRISC I0.39 (0.22 - 0.68)1.65.2LMWH vs placebo0.34 (0.20 - 0.58)5.79.6Gurfinkel (UFH)0.58 (0.17 - 1.98)27.330.5Holdright0.85 (0.51 - 1.43)09.6Gurfinkel (LMWH)0.13 (0.03 - 0.60)1.43.7RISC0.40 (0.11 - 1.39)0.12 (0.01 - 5.89)3.88.2Cohen0.46 (0.15 - 1.41)1.63.3Theroux0.50 (0.10 - 2.53)OR 95% CIUFH or LMWH in UA/NSTEMITrial: FRIC (dalteparin; n=1482)FRAXIS (nadroparin; n=2357)ESSENCE (enoxaparin; n=3171)TIMI IIB (enoxaparin; n=3910).751.01.5(P=0.032)(P=0.029)Braunwald E, et al. Circulation. 2000;102:1193-1209.LMWH BetterUFH BetterLMWH versus UFH in UA/NSTEMI: Effect on Death, MI, Recurrent IschemiaEndpoint Enoxaparin UFH Significant Death/MI (primary endpoint) (%)14 14.5 No Death (%) 3.2 3.1 No MI (%) 11.7 12.7 No Stroke 1.0 0.9 No Hemorrhagic stroke (%) 24 hours 1.7%  2.3%  2.8%GP IIb/IIIa Inhibitors: Reduction in Death/MI Associated with Time of Administration from Symptom OnsetIn-hospital Events by Early versus In-lab Only GP IIb/IIIa Inhibitor Use Adjusted OR 0.95; (95% CI 0.60–1.15)Adjusted OR 0.83; (95% CI 0.63–1.09)Peterson E. CRUSADE registry data. ACC Scientific Session; March 30-April 2, 2003; Chicago, Il.4.15%5.02%1.65% 1.32%0%1%2%3%4%5%6%DeathDeath/MIIn-lab Only GP IIb/IIIa (n=3642)Early GP IIb/IIIa (n=2191)Patients receiving PCI 4%Group 3=peak CK level between 181 and 360 IU/L, with MB fraction >4%. Abdelmeguid A, et al. Circulation. 1996;94:1528-1536.Freedom from Death: Cardiac En。