GUSTO 1 Trial 41 000 patients enrolled landmark
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GUSTO 1 Trial • 41, 000 patients enrolled, landmark study • t. PA improved rate of TIMI grade 3 flow by 20% over SK • t. PA lowered mortality by 1% compared to SK (7% vs 6%) • t. PA becomes most widely prescribed lytic, SK rarely if ever used • FDA uses 1% change in mortality as “benchmark” for equivalency studies because this magnitude of mortality reduction changed clinical practice • Subsequent trials required to demonstrate that 2 lytic agents within 1% of each other to demonstrate equivalency
Mortality Among 23, 230 Patients 6 Mo. Mortality (%) P< 0. 001
Recent Association of Myonecrosis with Mortality Among 23, 230 Patients P< 0. 001 vs Normal Relative Risk of Death Estimated 6 Mo. Mortality (%) Based on 3. 7% in Normals 6% of Pts Normal 1 -3 X 3 -5 X >5 X 19% of Pts Normal 1 -3 X 3 -5 X >5 X J Am Coll Cardiol 2003; 42: 1406 – 11
Multivariable Modeling of 30 -day Mortality Normal Peak CK-MB Other Variables: age, gender, region, weight, diabetes, hypertension, smoking status, worst CCS-class prior 6 weeks, prior CHF, prior MI, prior CVA, prior PVD, prior PTCA, prior CABG, heart rate, systolic BP, ST-depression, eptifibatide 1– 2 x ULN 2– 3 x ULN 3– 5 x ULN 5– 10 x ULN > 10 x ULN 0 1 2 3 4 5 6 7 Alexander JH et al. Circulation. 1999; Suppl 1: 1 -629.
Among Patients with a Stent and TIMI Grade 3 Flow Why Is The CK Elevated? Abnormal TMPG & 10 Fold Rise in CK Elevation Maximum CK-MB >2 x ULN (%) p = 0. 002 41. 2% Slow 10 fold rise in risk of MI Stain 4. 2% 1/24 Normal 14/34 Pale Even with a stent and TIMI 3 Flow, if you leave the cath lab with abnormal myocardial perfusion, risk of CK elevation goes up 10 fold Gibson CM et al, Am Heart J. 2002 Jan; 143(1): 106 -110.
TMPG and Maximum CK-MB 24 Hours Post-Stent All Patients Have TIMI 3 Flow at Completion of Stenting TIMI Grade 3 Flow: 100% Maximum CK-MB / Upper Limit of Normal CTFC 13 TIMI Grade 3 Flow: 100% p=0. 02 CTFC 17. 5 2. 23 + 2. 70 p = 0. 01 0. 78 + 0. 60 n = 24 TMPG 3 n = 34 TMPG 0, 1 , 2 Gibson, Am Heart J 2002
Among Patients with a Stent and TIMI Grade 3 Flow What Is The Association of Abnormal TMPG & Clinical Outcomes? 1 Year Death, MI, Urgent TVR 32. 4% Composite Event (%) p = 0. 01 Slow Stain 4. 2% 1/24 Normal 11/34 Pale Gibson CM et al, Am Heart J. 2002 Jan; 143(1): 106 -110.
TMPG and Maximum Troponin Post-stent All Patients Have TIMI 3 Flow at Completion of Stenting Maximum Troponin p = 0. 001 5. 3 Slow Stain 1. 5 Normal Pale Bolognese L et al, Circulation. 2004; 110: 1592 -1597.
