非st段抬高急性冠脉综合征

Berger China 10/051 Non-ST Elevation Acute Coronary Syndromes Peter Berger, MD Professor of Medicine Dir. Of Interventional Cardiology Duke University Medical Center and Duke Clinical Research Institute Durham, NC China October, 2005 Berger China 10/052 1.7 Million Hospital Discharges AHA. Heart Disease and Stroke Statistics2005 Update ACS STEMI Hospital Discharges for ACS Non-STE ACS vs STEMI NSTE ACS 1.4 Million Discharges/Yr 321,000 Discharge/Yr Berger China 10/053 NSTE ACS : Key Themes NSTE ACS: a high risk population patient risk benefit from treatment with medications, an invasive strategy Interaction between invasive strategy and pharmacologic tx Antithrombotics cornerstone of treatment Anticoagulants: heparin, LMWH, direct thrombin inhibitors Antiplatelet agents: aspirin, IIb/IIIa, ADP inhibitors Berger China 10/054 Baseline Characteristics NSTE ACS Patients: Recent RCTs and Large Registry Q2 2003 PURSUIT CUREGUSTO-IV ACSCRUSADE Characteristic (n = 9,461)(n = 12,562) (n = 7,800) (n = 5,426) Mean age SD (yrs) 63 1163 1265 1167 14 Diabetes mellitus (%) 23 23 22 33 Prior CHF (%) 11 8 8 19 Prior PCI (%) 13 - 10 22 Prior CABG (%) 12 18* 8 20 NEJM 1998;339:436; NEJM 2001;345:494 ; Lancet 2001;357:1915-24 * CABG or PTCA Antman EM et al N Engl J Med 1996;335:1342-9 Berger China 10/056 Berger China 10/057 3602401200 20 18 16 14 12 10 8 6 4 2 0 Cumulative probability of death 84 ml/min 51-66 ml/min 1869 ng/L 237-669 ng/L 65 years Male gender Diabetes mellitus Previous MI ST-depression Elevated troponin Elevated Il-6 / CRP Lagerqvist B et al Heart 2004 Berger China 10/0513 Benefits of an Invasive Strategy in Non-ST Elevation ACS Only shown to reduce death and MI in high risk pts Reduces re-hospitalization, angina in many others Shortens hospitalization, may be cost effective What about the optimal timing of an invasive strategy? Berger China 10/0514 Medical Tx for 72-170 hr Then, cath lab n=207 Cath lab 6 hr n=203 ISAR-COOL CP1107655-4Neumann FJ et al JAMA 2004 67% had troponin, 65% had ST depression Aspirin 500 mg, 100 mg bid Clopidogrel 600 mg, 75 mg bid Tirofiban 10 mg/kg bolus, 0.10 mg/kg/min infusion Heparin (PTT 60-85 seconds) Non-ST Acute Coronary Syndrome troponin or ST depression n=410 Berger China 10/0515 ISAR-COOL Primary Endpoint CP1107655-2 30-day event rate (%) Death 324:7186. OR* 0.5 1.0 1.5 2.0 5001500 mg 34 19 160325 mg 19 26 75150 mg 12 32 5g/dl, hypotension (inotropes), surgery to stop bleeding, symptomatic ICH or transfusion 4 units Berger China 10/0527 ACC/AHA ACS Guideline Update Class I ASA and clopidogrel for 9 months after NSTE ACS (level of evidence: B) Class 3 Do not administer clopidogrel in the 5 days before CABG Braunwald E, et al. Berger China 10/0528 Heparin (UF or LMW) in ACS Without ST Death or MI UFH or LMWH Control OR95% CI Theroux 2/122 (1.6%) 4/121 (3.3%)0.500.10-2.53 Cohen 0/37 1/32 (3.1%) 0.120.01-5.89 RISC 3/210 (1.4%) 7/189 (3.7%)0.400.11-1.39 Cohen 4/105 (3.8%) 9/109 (8.2%)0.460.15-1.41 Holdright* 42/154 (27.3%) 40/131 (30.5%) 0.850.51-1.43 Gurfinkel 4/70 (5.7%) 7/73 (9.6%) 0.580.17-1.98 (UFH) Gurfinkel 0/68 7/73 (9.6%) 0.130.03-0.60 (LMWH) FRISC 4/70 (5.7%) 36/757 (4.8%)0.390.22-0.68 UFH vs 55/698 (7.9%) 68/655 (10.4%)0.670.45-0.99 placebo/control LMWH vs 13/809 (1.6%) 43/830 (5.2%)0.340.20-0.58 placebo Total 68/1507 (4.5%) 104/1412 (7.4%)0.53 0.38-0.73 Only RCTs, placebo or untreated controls Eikelboom JW et al: Lancet 55:1936-42, 2000 CP951342-1 0.1 Heparin better 1.0 10.0 Control better Berger China 10/0529 Berger China 10/0530 Enoxaparin UFH (n = 4993) (n = 4985) Cath during hosp (%)92 92 Time to cath* 22 21 (hours) (6, 44) (6, 43) PCI 47 47 Time to PCI* 23 22 (hours) (6, 49) (6, 48) CABG (%) 19 18 Time to CABG* 91 89 (hours) (44, 167) (45, 166) Days hospitalized* 5 4 (3, 8) (3, 8) In-hospital Procedure s *Median (25th ,75th) Berger China 10/0531 SYNERGY Death or MI at 30 Days 0 5 10 15 20 25 300.8 0.85 0.9 0.95 1.0 Freedom from Death / MI Days from Randomization UFH Enoxaparin HR 0.96 (0.86-1.06) 1.1 Berger China 10/0532 SYNERGY Bleeding Events EnoxaparinUFH (n = 4993) (n = 4985)P-value GUSTO severe 07 TIMI major - clinical: 9.1 7.60.008 CABG-related 81 Non-CABG-related 2.4 1.70.025 Any RBC transfusion 17.016.00.155 ICH 5 min and ST 0.1 mV or Documented CAD or CK-MB N=132 Heparin 70 U/kg bolus + 15 U/kg/hr infusion Bivalirudin 0.1 mg/kg bolus + 0.25 mg/kg infusion TIMI - 8: Bivalirudin vs. Placebo in ACS Berger China 10/0539 TIMI - 8: Bivalirudin vs. Placebo in ACS 4-6 wks7 days 4-6 wks7 days p=0.008p=0.024p=NSp=NS Berger China 10/0540 Berger China 10/0541 Direct Thrombin Inhibitors in ACS CP999731-7 Being studied; currently little data Do use a DTI in ACS pts with heparin induced thrombocytopenia Bivalirudin if an invasive strategy is planned (safe but not approved for HIT) Lepirudin if a non-invasive strategy is planned (approved for HIT, not approved for PCI) Berger China 10/0542 Beta Blockers Reduce CV death, MI, stroke by 25- 30% in high risk pts Not well studied in non-STE ACS Reduce heart rate, blood pressure, ischemia, chest discomfort Class 1 indication; quality indicator Use in everyone without contraindications Berger China 10/0543 15.7 5.6 17.9 11.7 12.8 14.2 3.8 12.9 10.3 11.8 0 5 10 15 20 Primary Endpoint % Placebo GP IIb/IIIa PURSUIT 30 days PRISM 48 hrs PRISM PLUS 7 days P = 0.04 P = 0.01 P = 0.004 PARAGON A 30 days P = 0.48 PARAGON B 30 days P = 0.33 Platelet GP IIb/IIIa Inhibition for Non-ST ACS Primary Endpoint Results from the 5 Major RCTs Berger China 10/0544 1.0 2.00.25 All PCI trials 17,393 0.66 8.5 5.6 All ACS trials 24,311 0.89 12.8 11.4 ACS troponin (+) 1,368 0.42 16.3 6.9 ACS PCI 2,311 0.66 14.4 9.6 ACS no PCI 12,685 0.93 14.3 13.3 ACS troponin () 2,901 1.05 6.2 6.5 IIb/IIIa Meta-Analysis 30-Day Death, MI at 30 Days CP944328- 1 Relative risk Placebo IIb/IIIa No. ratio (%) (%) Chew DP et al: JACC 2000;36:2028 35 IIb/IIIa better Placebo better Berger China 10/0545 IIb/IIIa Inhibitors in ACS Patients Greatest benefit is during PCI If pursuing a non-invasive strategy, recommend treating pts with elevated troponins, high TIMI, FRISC scores, etc; probably those with diabetes, marked ST segment shifts Do not recommend their routine administration to all ACS pts in whom a non-invasive strategy is planned Berger China 10/0546 TENACITY Tirofiban Evaluation of Novel Dosing vs. Abciximab with Clopidogrel and Inhibition of Thrombin Study Intermediate to High-risk PCI Patients Aspirin + High-dose Clopidogrel Intent-to-stent N 8,000 Tirofiban Abciximab Heparin BivalirudinHeparin Bivalirudin Stoppe