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1、Acute Coronary Syndromes: Management of UA/NSTEMI,Overview of 2003 Updates to the ACC/AHA Guideline for UA/NSTEMI,Assess likelihood of CAD Risk stratification Target therapy: more aggressive treatment in higher-risk patients Anti-ischemic, antithrombotic therapy Invasive vs conservative strategy Dis
2、charge planning (risk factor modification and long-term medical therapy),ACC/AHA, American College of Cardiology/American Heart Association; UA, unstable angina; NSTEMI, nonST-segment elevation myocardial infarction. Braunwald E, et al. J Am Col. Cardiol. 2000;36:970-1062.,Acute Management of UA/NST
3、EMI,Anti-Ischemic Therapy Oxygen, bed rest, ECG monitoring Nitroglycerin -Blockers ACE inhibitors,UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial infarction; ECG, electrocardiogram; ACE, angiotensin-converting enzyme. Braunwald E, et al. J Am Coll Cardiol. 2000;36:970-1062.,Antithro
4、mbotic Therapy Antiplatelet therapy Anticoagulant therapy,Possible ACS,Aspirin,Aspirin + IV Heparin + IV Platelet GP IIb/IIIa Antagonist,Definite ACS With Invasive Strategy (Catheterization/PCI) or High Risk (IIa)*,Clopidogrel,Aspirin + SQ LMWH* or IV Heparin,Likely/Definite ACS,Clopidogrel,* Class
5、IIa: enoxaparin preferred over UFH unless CABG planned within 24 hours. ACC, American College of Cardiology; AHA, American Heart association; ACS, acute coronary syndrome; PCI, percutaneous coronary intervention; SQLMWH, subcutaneous low molecular-weight heparin; IV, intravenous. Braunwald E, et al.
6、 J Am Coll Cardiol. 2000;36:970-1062.,ACC/AHA Class I Recommendations for Antithrombotic Therapy*,17.1,6.5*,Placebo,ASA,0,5,10,15,20,Patients (%),Unstable Angina,25.0,11.0*,ASA,0,10,20,30,3.3,1.9*,ASA,0,1,2,3,4,11.8,9.4*,ASA,0,5,10,15,Acute MI,Aspirin in Acute Coronary Syndromes,*P.0001 Death or MI,
7、*P=.003 Reocclusion,*P=.012 MI,*P.001 Death,N= 397 399 513 419 8587 8600 8587 8600,MI, myocardial infarction; ASA, acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease. RISC Group. Lancet. 1990;336:827-830. Roux S, et al. J Am Coll Cardiol. 1992;19:671-677. ISIS-2. Lancet.
8、1988;2:349-360.,Placebo,Placebo,Placebo,Aspirin in Acute Coronary Syndromes,12.9,3.9*,ASA,0,5,10,15,11.9,3.3*,ASA,0,5,10,15,12.9,6.2*,ASA,0,5,10,15,2.2,1.3*,ASA,0,0.5,1,1.5,2,2.5,UA/NSTEMI,Primary Prevention,Stable Angina,*P.0001 MI,*P=.0003 MI,*P=.008 Death or MI,*P=.012 Death or MI,N= 11034 11037
9、155 178 279 276 118 121,MI, myocardial infarction; ASA, acetylsalicylic acid; RISC, Research on InStability in Coronary artery disease; ISIS-2, Second International Study of Infarct Survival. PHS. N Engl J Med. 1989;321:129-35. Ridker PM, et al. AJC. 1991;114:835-839. Cairns JA, et al. N Engl J Med.
10、 1985;313:1369-1375. Theroux P, et al. N Engl J Med. 1988;319:1105-1111.,Placebo,Placebo,Placebo,Placebo,Patients (%),Indirect Comparisons of ASA Doses on Vascular Events in High-Risk Patients,* Odds reduction. Treatment effect P.0001. ASA, acetylsalicylic acid. Adapted with permission from BMJ Publ
11、ishing Group. Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86.,0.5,1.0,1.5,2.0,500-1500 mg 34 19,160-325 mg 19 26,75-150 mg 12 32,75 mg 3 13,Any aspirin 65 23,Antiplatelet Better,Antiplatelet Worse,Aspirin Dose No. of Trials (%),Odds Ratio,0,OR*,BRAVO: Bleeding By ASA dose,Topol EJ, et a
12、l. Circulation. 2003;108:399-406. (with permission),Outcomes by Aspirin Dose in Placebo Study Drug Patients,Low Dose, 75-162 mg/d (n=2410),Higher Dose, 162 mg/d (n=2179),Primary end point 16.4 18.6 Death, MI, stroke 6.2 6.1 Death 2.8 1.7 MI 2.0 2.1 Stroke 2.1 2.8 Urgent hospital care 9.5 10.6 Urgent
13、 resuscitation 7.3 10.0 Internal bleeding 2.4 3.3 Any bleeding 11.1 15.4 Transfusion 1.0 2.0,Clopidogrel + ASA (N=6259),Placebo + ASA* (N=6303),CURE: Major Bleeding at 1 year by ASA Dose,200 mg (N=4110) 3.7% 4.9% P value for trend .0001 .0009,* P=.0001. P=.0009. Adapted from Peters RJG, et al. Circu
14、lation. 2003;108:1682-1687.,ASA Dose,RR: Death/MI,ASA Alone 68/655=10.4%,Heparin + ASA 55/698=7.9%,B,B,B,B,B,B,B,0.1,1,10,Summary Relative Risk,0.67 (0.44-0.1.02),Theroux,RISC,Cohen 1990,ATACS,Holdright,Gurfinkel,Comparison of Heparin + ASA vs ASA Alone,ASA, acetylsalicylic acid; RISC, Research on I
15、nStability in Coronary artery disease; ATACS, Antithrombotic Therapy in Acute Company Syndromes; RR, relative risk; MI, myocardial infarction. Oler A, et al. JAMA. 1996;276:811-815. (with permission),TIMI, Thrombosis in Myocardial Infarction; ESSENCE, Efficacy and Safety of Subcutaneous Enozapam in
16、NonQ-Wave Coronary Events; UHF, unfractionated heparin; ENOX, enoxaparin; MI, myocardial infarction; OR, odds ratio. Antman EM, et al. Circulation. 1999;100:1602-1608. (with permission),TIMI IIB/ESSENCE Metanalysis: Enoxaparin vs Unfractionated Heparin,UHF, unfractionated heparin; ENOX, enoxaparin;
17、RRR, relative risk ratio. Antman EM. Circulation. 1999;100:1593-1601. (with permission),TIMI IIB: Early Phase Death/MI/Urgent Revasc,UFH,Enoxaparin,P=.03,Major Bleeds96 Hours,INTERACT: Enoxaparin vs Unfractionated Heparin With GP IIb/IIIa Inhibitors,Goodman SG, et al. Circulation. 2003;107:238-244.,
18、Death/MI30 Days,P=.031,UFH,Enoxaparin,Percent,A-Phase Study Design,UA/ NSTEMI,Final A visit 30 days,Randomize,- 24 hours,Chest pain,Min 0 hour Max 120 hour,Tirofiban + ASA,Hour 0,Aggressive or conservative care per local practice,2026,1961,ENOX 1mg/kg q12 hr,UFH Weight-adjusted,Z,Z,Treat & Evaluate
19、for Z-Phase,2018,1952,3987,1 endpoint 7 days,Blazing M. presented at ACC 2003.,0,10,20,30,0,2,4,6,8,10,12,UFH,Enoxaparin,UFH,ENOX,Days From Randomization,Event Rates (%),Day 7,8.4% (169 events),9.4% (184 events),7- and 30-Day Primary Endpoint Composite Death, MI and Refractory Ischemia,Blazing M. pr
20、esented ACC 2003.,Enox Test vs Outcomes,Moliterno DJ, et al. JACC. 2003;42:1132-1139. (with permission),Death/MI/Urg TVR Bleeding,30,25,20,15,10,5,0,200,250,300,350,400,450,500,550,600,200,250,300,350,400,450,500,550,600,Probability of MACE (%),Probability of Any Bleeding (%),30,25,20,15,10,5,0,ENOX
21、 Time (sec),ENOX Time (sec),Direct Thrombin Inhibitor Trialists Collaboration,Direct Thrombin Inhibitor Trialists Collaborative Group. Lancet. 2002;359:294-302. (with permission),11 RCTS 36,000 Pts ACS, PCI,Death or Myocardial Infarction,Direct Thrombin Inhibitor Heparin (N=18,736) (N=17,184),OR (95
22、% Cl),End of treatment 7 days 30 days,End of treatment 7 days 3 days,Death,Myocardial Infarction,End of treatment 7 days 30 days,End of treatment 7 days 30 days,Stroke,Major bleeding during treatment Intracranial bleeding during treatment,815 (4.3%) 883 (5.1%) 947 (5.0%) 990 (5.8%) 1399 (7.4%) 1409
23、(8.2%),355 (1.9%) 346 (2.0%) 422 (2.2%) 395 (2.3%) 685 (3.6%) 642 (3.7%),522 (2.8%) 596 (3.5%) 601 (3.2%) 672 (3.9%) 876 (4.7%) 917 (5.3%),62 (0.33%) 60 (0.35%) 72 (0.38%) 70 (0.41%) 120 (0.64%) 110 (0.64%) 360 (1.90%) 403 (2.30%) 21 (0.11%) 28 (0.16%),0.85 (0.77-0.94%) 0.88 (0.80-0.96%) 0.91 (0.84-
24、0.99%),0.97 (0.83-1.13%) 1.00 (0.87-1.16%) 1.01 (0.90-1.12%),0.80 (0.71-0.90%) 0.81 (0.72-0.91%) 0.87 (0.79-0.95%),0.95 (0.66-1.35%) 0.94 (0.68-1.31%) 1.01 (0.78-1.31%) 0.75 (0.65-0.87%) 0.72 (0.42-1.23%),Early invasive strategy,+/- GP IIb/IIIa,Catheterization within 8 hours of last subcutaneous dos
25、e,UA/NSTEMI Identified, LMWH,- GP IIb/IIIa,+ GP IIb/IIIa,Catheterization between 8-12 hours of last subcutaneous dose,No additional UFH or LMWH,Additional Enoxaparin 0.3 mg/kg IV bolus,Supplement with UFH 50 U/kg, aim for ACT 200-250,Supplement with UFH 60 U/kg, aim for ACT 250-300,Additional Enoxap
26、arin 0.3-0.5 mg/kg IV,Kereiakes DJ, et al. Am Heart J. 2002;144:615-624. (with permission),Expert Panel Consensus,GP IIb/IIIa Inhibitor During Medical Management and After PCI: CAPTURE, PURSUIT, PRISM-PLUS,0%,2%,4%,6%,8%,10%,PCI,N=2754 P=.001,N=12,296 P=.001,+24 h,+48 h,+72 h,+24 h,+48 h,Boersma E,
27、et al. Circulation. 1999;100:2045-2048. (with permission),4.3%,2.9%,8.0%,4.9%,Death or MI,Medical Rx,Post PCI,Control GP IIb/IIIa inhibitor,0,Meta-analysis of IIb/IIIa Inhibition in PCI for 30-Day Mortality,Kong DF, et al. Am J Cardiol. 2003;92:651-655. (with permission),P=.024,OR,EPIC EPILOG RAPPOR
28、T CAPTURE Impact I Impact II Restore Epistent Espirit ISAR 2 Admiral Cadillac Combined,N 2099 2792 483 1265 150 4010 2141 2399 2064 401 300 2082 20186,Trt 1.5 0.4 2.5 1.0 1.0 0.7 0.8 0.5 0.4 2.0 3.4 1.9 0.9,Ctrl 1.7 0.7 2.1 1.3 2.0 1.1 0.7 0.6 0.6 4.5 6.6 2.3 1.3,IIb/IIIa Inhibitor Better,Placebo Be
29、tter,0.73 (0.55,0.96),0.1,1,10,IV GP IIb/IIIa Inhibitors in ACS: Death or MI at 30 Days (N=31,402),PRISM 7.1% 5.8%* 0.80 0.60-1.06 PRISM-PLUS 12.0% (*) 8.7% 0.70 0.50-0.98 ( ) 13.6%* 1.17 0.80-1.70 PARAGON-A 11.7% (l) 10.3% 0.87 0.58-1.29 (h) 12.3% 1.06 0.72-1.55 PURSUIT 15.7% (l) 13.4% 0.83 0.70-0.
30、99 (h) 14.2% 0.89 0.79-1.00 PARAGON-B 11.4% 10.6% 0.92 0.77-1.09 GUSTO-IV 8.0% (24h) 8.2% 1.02 0.83-1.24 (48h) 9.1% 1.15 0.94-1.39 Overall 11.8% 10.8%t 0.91 0.85-0.98,Odds Ratio,Placebo,IV Gp IIb/IIIa,95% CI,Placebo Better,Gp IIb/IIIa Better,0,1.0,2.0,Study,P=.015,* Without heparin. With/without hep
31、arin. (l), Low dose; (h), High-dose. Boersma E, et al. Lancet. 2002;359:189-198.,Benefit of IIb/IIIa inhibitors in UA/NSTEMI by Troponin,UA, unstable angina; NSTEMI, nonST-segment elevation myocardial infarction; CAPTURE, Chimeric-7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard tr
32、eatment; PRISM, Platelet Receptor Inhibition for Ischemic Syndrome Management Study; TnT, tropponin T level; TnI, troponin I level. Hamm CW, et al. N Engl J Med. 1999;340:1623-1629. Heeschen C, et al. Lancet. 1999;354:1757-1762.,TnI 0.1 g/L,Death or MI at 30 days (%),GP IIb/IIIa Inhibition in TnI +
33、Patients by Revascularization: PRISM Study,TnI, troponin I; PRISM, Platelet Receptor Inhibition for Ischemic Syndrome Management study; MI, myocardial infarction. Heeschen C, et al. Lancet. 1999;354:1757-1762. (with permission),Death/MI at 30 Days,0.37 (0.15-0.93) P =.02,0.30 (0.10-0.84) P =.004,16,
34、12,8,4,0,0,5,10,15,20,25,30,Event rate (%),Follow-up (days),No revascularization,Revascularization,Heparin Heparin Tirofiban Tirofiban,GP IIb/IIIa Inhibition in Diabetics,Roffi M, et al. Circulation. 2001;104:2767-2771. (with permission),30-Day Mortality in Diabetic Patients,2163 687 362 1677 412 11
35、57 6458,PURSUIT PRISM PRISM-PLUS GUSTO IV PARAGON A PARAGON B Pooled,6.1% 4.2% 6.7% 7.8% 6.2% 4.8% 6.2%,5.1% 1.8% 3.6% 5.0% 4.6% 4.9% 4.6%,P=.33 P=.07 P=.17 P=.022 P=.51 P=.93 P=.007,Trial N Odds Ratio & 95% Cl Placebo IIb/IIIa,Breslow-Day: P=.50 IIb/IIIa Better Placebo Better OR=0.74,0 0.5 1 1.5 2,
36、Intravenous GP IIb/IIIa Antagonists in ACS: Death or MI (at 30 Days) in PCI/CABG 5 Days Cohort and in Medical Treatment Cohort,17.3,10.5,14.3,10.1,0,2,4,6,8,10,12,14,16,18,20,Intervention,Medical Treatment,Death or MI,Placebo,IV GP IIb/IIIa,P=.001,P=NS,(N=5847),(N=25,555),ACS, acute coronary syndrom
37、e; MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; NS, not significant. Boersma E, et al. Lancet. 2002;359:189-198.,Interaction P.02,GP Iib/IIIa Inhibitor NSTE ACS Trials Analysis Risk-Adjusted Mortality at 30 Days,Peterson ED, et al. J Am Coll
38、 Cardiol. 2003;42:45-53. Boersma E, et al. Lancet. 2002;359:189-198.,0.5,2.0,1.0,NRMI1,Boersma2,0.83-1.01,0.91,0.79-0.97,0.88,95% CI,Odds Ratio,Odds Ratio for Mortality at 30 Days,GP IIb/IIIa Inhibitor Favored (aspirin + heparin),Control Arm Favored (aspirin + heparin),Mortality by Hospitals Use of
39、Early GP IIb/IIIa Inhibitors (N=1189 Hospitals),Hospital Use of Early GP IIb/IIIa inhibitors in NRMI (%),In-Hospital Mortality (%),5,5-15,16-30,30,14,12,10,8,6,4,2,0,NRMI, National Registry of Myocardial Infarction. Peterson ED, et al. J Am Coll Cardiol. 2003;42:45-53. (with permission),In-Hospital
40、Mortality (%),Efficacy of Clopidogrel or Ticlopidine in Reducing Coronary Events After Stenting,CLASSICS, Clopidogrel Aspirin Stent Intervention Coopoerative Study. Bhatt DL, et al. J Am Coll Cardiol. 2002;39:9-14. (with permission),30-Day Major Adverse Cardiac Events,Odds Ratio & 95% CI,Ticlopidine
41、 Better,Clopidogrel Better,Trial,Clopid. (%),Ticl. (%),N,Overall,13,955,2.0,3.9,0.1,1,10,TOPPS,CLASSICS,1016,1020,2.6,1.3,3.5,0.9,Lenox Hill,CCF,2565,2369,2.4,5.7,3.8,8.9,Mller,700,3.1,1.7,Wessex,-361,3.4,5.2,N. Memorial,1378,0.8,2.2,S. Illinois,875,2.1,1.4,Wash. Hosp.,844,2.0,0.5,Mayo,2827,0.6,1.6,
42、OR=.73, P=.003,CURE, Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events; MI, myocardial infarction; CV, cardiovascular; RRR, relative risk reduction. Plavix package insert; 2002. Adapted with permission (2002) from the Massachusetts Medical Society. Yusuf S, et al. N Engl J Med. 200
43、1;345:494-502.,CURE: Primary End Point MI/Stroke/CV Death,CURE: MI/Stroke/CV Death/Severe Ischemia Within 24 Hours of Randomization,CURE, Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events; MI, myocardial infarction; CV, cardiovascular; RRR, relative risk reduction; RR, relative ris
44、k. Adapted from Yusuf S, et al. Circulation. 2003;107:966-972.,CURE, clopidogrel in Unstable Angina to Prevent Ischemic Events; TIMI, Thrombosis in Myocardial Infarction; CV, cardiovascular; MI, myocardial infarction; RRR, relative risk reduction; ARR, Absolute risk reduction. * In addition to other
45、 standard therapies. Budaj A, et al. Circulation. 2002;106:1622-1626. (with permission),Primary Composite End Point (CV Death, MI, Stroke),CURE: Benefit of Clopidogrel + Aspirin Across All TIMI Risk Score Groups,PCI-CURE: Study Design,CLOPIDOGREL + ASA*,PCI,PLACEBO + ASA*,Open-label thienopyridine,P
46、retreatment,Open-label thienopyridine,Pretreatment,N=2658 patients undergoing PCI,N=1345,N=1313,CURE,PCI-CURE,R,Mehta SR, et al. Lancet. 2001;358:527-533.,30 days post-PCI,End of follow-up up to 12 months after randomization,PCI CURE: Benefit of Pretreatment With Clopidogrel at 30 Days,0,5,10,15,20,
47、25,30,Follow-up (days),0.0,0.02,0.04,0.06,0.08,30% RRR P=.03 N=2658,Cumulative Hazard Rate,Mehta SR, et al. Lancet. 2001;358:527-533. (with permission),6.4%,4.5%,Clopidogrel + ASA,Placebo + ASA,Cardiovascular Death, MI, or Urgent Revascularization,Adapted from Mehta SR, et al. Lancet. 2001;358:527-533. (with permission),CV Death or MI From Randomization to End of F