Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time The Management of Acute Myocardial Infarction Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time Early Repolarization Brugada Syndrome Anterior AMI Prinzmetal Angina Pericarditis Acute Inf AMI ST Segment Elevation Transmural ischemia Non infarct ST Elevation Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time ST Segment Depression Non transmural ischemia ST Depression NSTEMI T wave inversion NSTEMI Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time 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 Antman EM et al N Engl J Med 1996 335 1342 9 Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time Invasive vs Conservative Strategy for ACS Death or re MI Trial N PCI ConsTrial N PCI Cons RITA 3 1810 7 6 8 3RITA 3 1810 7 6 8 3 VINO 131 6 3 22 4VINO 131 6 3 22 4 TACTICS 2220 7 3 9 5TACTICS 2220 7 3 9 5 TRUCS 148 7 6 16 7TRUCS 148 7 6 16 7 FRISC II 2451 10 4 14 1FRISC II 2451 10 4 14 1 MATE 201 9 9 6 7MATE 201 9 9 6 7 VANQUISH 920 24 0 12 2VANQUISH 920 24 0 12 2 Overall 7876Overall 7876 Fox Lancet 360 743 03Fox Lancet 360 743 03 Death re Infarction RR 0 88 p 0 05RR 0 88 p 0 05 Intervention betterIntervention better 0 1 0 2 0 3 0 5 0 7 1 0 1 5 2 00 1 0 2 0 3 0 5 0 7 1 0 1 5 2 0 Death re MIDeath re MI Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time CP971744 45 Cons Cons InvInv TACTICS TIMI 18 TnT cut point 0 01 ng mL 54 of pt TnT Troponin T Death MI Rehosp ACS 6 Months OR 0 52OR 0 52 P 0 001 P 0 001 InteractionInteraction P 0 001P 0 001 P NSP NS n 414 n 396n 463n 495 Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time Benefits of an Invasive Strategy in Non ST Elevation ACS Only shown to reduce death and MI in Only shown to reduce death and MI in high risk ptshigh risk pts Reduces re hospitalization angina in Reduces re hospitalization angina in many othersmany others Shortens hospitalization may be cost Shortens hospitalization may be cost effectiveeffective What about the optimal timing of an What about the optimal timing of an invasive strategy invasive strategy Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time Medical Tx for 72 170 hr Then cath lab n 207 Cath lab 6 hr n 203 ISAR COOL CP1107655 4 Neumann FJ et al JAMA 2004Neumann 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 Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time ISAR COOL Primary Endpoint CP1107655 2 30 day event rate Death 324 71 86 2002 324 71 86 OR 0 51 01 52 0 500 1500 mg34 19 160 325 mg19 26 75 150 mg12 32 75 mg3 13 Any aspirin65 23 Antiplatelet BetterAntiplatelet Worse Aspirin DoseNo of Trials Odds Ratio 0 Aspirin Dose and Events in High Risk Pts Frequency of CV Death MI Stroke P 0 0001 Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time CURE CP999547 2 Yusuf S et al NEJM 2001 16 494 502 Non ST elevation ACSNon ST elevation ACS 12 562 patients12 562 patients ASA 75 to 325 mg po qdASA 75 to 325 mg po qd placeboplacebo n 6 303n 6 303 3 12 month follow up3 12 month follow up average 9 mo average 9 mo ASA clopidogrelASA clopidogrel 300 mg load 75 mg qd 300 mg load 75 mg qd n 6 259n 6 259 Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time CURE CV Death MI Stroke 1 Year CP999731 3 CV death MI stroke Clopidogrel n 6 303 Placebo n 6 259 P 0 00003 Days after enrollment Our greatest weakness lies in giving up The most certain way to succeed is always to try just one more time CURE EventEvent raterate RR 0 80RR 0 80 P 0 00005P 0 00005 CP995058 6 CV death CV death MI strokeMI stroke Clopidogrel n 6 259 Clopidogrel n 6 259 Placebo n 6 303 Placebo n 6 303 Aspirin andAspirin and CVCV deathdeath MIMIStrokeStrokeNon CVNon CV deathdeath RR 0 92RR 0 92 P NSP NS RR 0 77RR 0 77 P 0 001P 5g dl hypotension 5g dl hypotension inotropes surgery to stop bleeding inotropes surgery to stop bleeding symptomatic ICH or transfusion