PROTECT: What Have We Learned Lesson 2: TMPG is associated with clinical and biomarker outcomes following PCI Association of Post PCI TMPG 3 with Adverse Outcomes % p=0.005 p=0.084 p=0.011 TMPG 0,1,2n=327 TMPG 3n=411 Association of CFR and Post-PCI TMPG with Clinical, Biomarker and Holter Outcomes D/MI/Ischemia 1.38 (-) vs 1.29 (+); P= % vs 11.4%; p=0.005 D/MI 1.38 (-) vs 1.25 (+); P= % vs 5.6%; p=0.084 Holter 1.36 (-) vs 1.36 (+); P= % vs 7.0%; p=0.011 Duration of Holter (Min) Rho = ; P= vs ; p=0.034 Baseline tn 1.36 (tn-) vs 1.39 (tn+); P= vs 0.12; p=0.017 Rise in tn Rho = ; p= vs 0.15; p=0.89 Peak tn Rho = ; P= vs 0.65; p=0.033 Post PCI tn (-) vs 1.45 (+); P= vs 72.2%; p=0.08 Baseline CK-MB Rho = ; p= vs 1.0; p=0.048 Rise in CK-MB Rho = ; p= vs 0.5; 2 way p=0.31; 4 way of all TMPGs p=0.044 Peak CK-MB Rho = ; P= vs 2.3; p=0.017 Post PCI CK-MB (CKMB-) vs 1.40 (CKMB+); p= % vs 30.5%; p=0.018 Coronary Flow Reserve (CFR) TMPG 0,1,2 vs TMPG 3 Multivariate Model Of Death / MI / Ischemia on Holter Through 48 Hours Odds ratio of death / MI / Ischemia on Holter 1.7 (95% CI , p=0.017) for closed muscle (TMPG 0,1,2) when adjusting for post PCI CFR (p=0.27, NS) Lesson 3: What is the most powerful predictor of the baseline troponin before PCI? Impaired Myocardial Perfusion on the Diagnostic Cath Circulation 2002;106: Association of Baseline Troponin I with the Pre-PCI TMPG Troponin I p< Median: 0.36 Mean Median: 0.07 Mean N=289 N=362N=362 Odds of leaving cath lab with an open muscle were 6.2 times higher if you arrive to lab with an open muscle (p 6 hours p=NS Non-significant covariates: age (p=0.49); gender (p=0.42); race (p=0.51); prior CHF (p=0.67); prior MI (p=0.69); history of angina (p=0.46); prior stenosis > 50% (p=0.98); prior PCI (p=0.26); history of CABG (p=0.35); known EF 1.0 mm (p=0.75); systolic BP at randomization (p=0.64); diastolic BP (p=0.27); heart rate (p=0.92); weight (p=0.83); prior ASA use (p=0.95); prior beta blocker use (p=0.70); prior ACE use (p=0.93); prior Ca channel blocker use (p=0.37); prior ARB (p=0.91); prior nitrates (p=0.50); pre-PCI TIMI Flow Grade (p=0.84). Multivariate Correlates of Post-PCI TMPG 3 Variable Multivariate p value Pre-PCI TMPG 3 p 6 hours p=0.14 History of Dyslipidemia p=0.56 Culprit artery location Compared to LAD OR for LCx = 1.74 (p=0.025); OR for RCA = 0.99 (p=0.98); OR for diagonal / ramus = 2.93 (p=0.023) Gray per sec P=0.05 N=27 N=18 Rate of Increase in DSA Brightness (Gray /sec) Rate of Increase in DSA Brightness (Gray /sec) ESPRITESPRIT Heparin Heparin + Eptifibatide Gibson CM et al, AJC 2001;87(11): p = Index of Absolute Number of 2b3a Receptors Unoccupied 51.2 24.8K Median 54.0K 51.2 24.8K Median 54.0K Post PCI TMPG 2/3 Post PCI TMPG 0/ K Median 67.8K K Median 67.8K n=26 n=21 Count (in thousands) INTEGRITIINTEGRITI Gibson CM et al, Circulation. 2004;110: N = 253 % TMPG 3 p = Upstream Duration (> median) Upstream Duration (> median) Gibson. Am J Cardiol. 2004; 94:492-4 Prior Studies Linking GP IIbIIIa Inhibition and Improved Myocardial Perfusion Longer / Earlier Upstream GPIIbIIIa Inhibition Improves Rate of TMPG3 TACTICSTACTICS GP IIbIIIa Inhibition was Associated with a More Rapid Rate of Rise in Myocardial Contrast ECHO (MCE) Intensity Following Reperfusion in Animal Model Kunichika, Demaria A et al, J Am Coll Cardiol 2004;43:27683 Prior Studies Linking GP IIbIIIa Inhibition and Improved Myocardial Perfusion PROTECT: What Have We Learned Lesson 5: Abnormal myocardial perfusion post-PCI is related to ischemia post-PCI, and Eptifibatide significantly reduces the duration of ischemia compared to Bivalirudin when it does occur Association of Post PCI TMPG 3 with Holter Findings % Ischemia TMPG 0,1,2n=327 TMPG 3n=411 Duration (min) p=0.034 p=0.011 TMPG 0,1,2 TMPG 3 CAPTURE & PROTECT Trials Holter Substudies Klootwijk, Circulation 1998;98: Total Duration ST Depression Per Patient (min) p=0.10 HeparinAbciximabBivalirudin Integrilin + UFH or Enox P=0.013 CAPTURE PROTECT