1. Clinical Trial Results. org Intracoronary Streptokinase after Primary Percutaneous Coronary Intervention Murat Sezer, Hüseyin Oflaz, Taner Gören, Irem Okcular, Berrin Umman, Yılmaz Nişancı, Ahmet Kaya Bilge, Yasemin Şanlı, Mehmet Meriç, Sabahattin Umman Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology ICSK after Primary PCI

2. Clinical Trial Results. org Rationale of the study From Epicardial Coronaries… Primary percutaneous coronary intervention (PCI) is the most effective reperfusion method in the treatment of STEMI.Primary percutaneous coronary intervention (PCI) is the most effective reperfusion method in the treatment of STEMI. Nevertheless, processes causing myocardial damage are not immediately terminated despite elimination of epicardial occlusion with successful primary PCI.Nevertheless, processes causing myocardial damage are not immediately terminated despite elimination of epicardial occlusion with successful primary PCI. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

3. Clinical Trial Results. org Rationale of the study From Epicardial Coronaries… It has been presumed that mechanisms of reperfusion injury including embolization of epicardial thrombus and plaque content to microvasculature are responsible for this ongoing damage.It has been presumed that mechanisms of reperfusion injury including embolization of epicardial thrombus and plaque content to microvasculature are responsible for this ongoing damage. Unfortunately, almost all of the previous studies based on these hypothesis and aiming to stop reperfusion injury have not been succeeded.Unfortunately, almost all of the previous studies based on these hypothesis and aiming to stop reperfusion injury have not been succeeded. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

4. Clinical Trial Results. org …to the Microvasculature There is a growing evidence pointing concordance between myocardial and microvascular damage in STEMI patients.There is a growing evidence pointing concordance between myocardial and microvascular damage in STEMI patients. Microvascular damage might not be only an accompanying process to the myocardial damage. Also there might be a causal relationship in between.Microvascular damage might not be only an accompanying process to the myocardial damage. Also there might be a causal relationship in between. If one focused to microvasculature during peri-PCI procedure, it can be easily realized that another and important contributor might have a role in this process.If one focused to microvasculature during peri-PCI procedure, it can be easily realized that another and important contributor might have a role in this process. insitu microvascular thrombus! Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

5. Clinical Trial Results. org Virchow’s Triad and Autochthonous Thrombus All three components of Virchow’s triad (blood constituent, endothelial damage and stasis) exist at extreme levels in the microvasculature of infarcted myocardium.All three components of Virchow’s triad (blood constituent, endothelial damage and stasis) exist at extreme levels in the microvasculature of infarcted myocardium. Therefore, in situ (de-novo) formed fraction may constitute the main part of the thrombus located in infarct site’s microvasculature.Therefore, in situ (de-novo) formed fraction may constitute the main part of the thrombus located in infarct site’s microvasculature. Virchow RR. Cellular Pathology. London, Churchill, 1860. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

6. Clinical Trial Results. org Coronary Vascular Resistance If epicardial and microvascular vessels are considered as serially connected resistances, elimination of the proximal epicardial occlusion and retrieval of whole epicardial thrombus would not be enough to normalize total coronary resistance and perfusion at affected segments.If epicardial and microvascular vessels are considered as serially connected resistances, elimination of the proximal epicardial occlusion and retrieval of whole epicardial thrombus would not be enough to normalize total coronary resistance and perfusion at affected segments. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

7. Clinical Trial Results. org Hypothesis Complementary intracoronary streptokinase (ICSK) infusion immediately following primary PCI may further improve tissue level perfusion by dissolving thrombus (either in situ formed or embolized from the proximal origin) at microvascular level.Complementary intracoronary streptokinase (ICSK) infusion immediately following primary PCI may further improve tissue level perfusion by dissolving thrombus (either in situ formed or embolized from the proximal origin) at microvascular level. To this end, the effect of low-dose (250 kU) ICSK, administered immediately after primary PCI, on myocardial perfusion was investigated prospectively.To this end, the effect of low-dose (250 kU) ICSK, administered immediately after primary PCI, on myocardial perfusion was investigated prospectively. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

8. Clinical Trial Results. org Inclusion/Exclusion Criteria Inclusion criteria:Inclusion criteria: –Ongoing chest pain, –ST segment elevation on electrocardiogram, –Occlusion of the infarct-related artery at angiography (Thrombolysis in Myocardial Infarction [TIMI] 0-I flow) Exclusion criteria:Exclusion criteria: –Culprit lesion in a saphenous vein graft, –Additional narrowing >50% distal to the culprit lesion, –Left bundle branch block, –History of prior myocardial infarction, and –Contraindications to streptokinase, tirofiban, aspirin, clopidogrel or heparin. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

9. Clinical Trial Results. org Patients and Randomization Immediately after diagnostic angiography eligible patients (n =41) were randomized to ICSK group (n=21)Control group (n=20) (Primary PCI + 250 kU intracoronary streptokinase) (primary PCI) (Primary PCI + 250 kU intracoronary streptokinase) (primary PCI) All patients recieved: All patients recieved: - 300 mg of aspirin, - A loading dose of 600 mg of clopidogrel, - Intracoronary unfractioned heparin at a dose of 100 U/kg during the procedure, - Tirofiban as a bolus of 0.1 μg/kg in 3 minutes followed by continuous infusion of 0.15 μg/kg/min for 12 hours, and - Low molecular weight heparin initiated four to five hours after primary PCI and continued for at least 48 hours Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

10. Clinical Trial Results. org All patients underwent intracoronary hemodynamic measurement and angiographic analysis two days after primary PCI to evaluate microvascular function ST segment resolution Diastolic deceleration time Echocardiographic assessment of left ventricular volumes and function Coronary flow reserve Index of microvascular resistance Coronary wedge pressure (mean ad systolic) Pressure derived collateral flow index Myocardial blush grades Corrected TIMI frame count All patients underwent intracoronary hemodynamic measurement and angiographic analysis two days after primary PCI to evaluate microvascular function ST segment resolution Diastolic deceleration time Echocardiographic assessment of left ventricular volumes and function Coronary flow reserve Index of microvascular resistance Coronary wedge pressure (mean ad systolic) Pressure derived collateral flow index Myocardial blush grades Corrected TIMI frame count Study Design Second angiography and intracoronary hemodynamic measurements 2 days after AMI. Assesing microvascular perfusion and LV volumes in early phase of STEMI Control angiography (TIMI frame count, Myocardial blush grade) Infarct size measurement (SPECT), Echocardiographic assessment of left ventricular volumes and function Long term assesments (at 6 months) Transthoracic echocardiography, 2 days after AMI Pre/post PCI ECG Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

11. Clinical Trial Results. org Assessment of Microvascular Perfusion by Invasive Methods Thermodilution-derived Coronary Flow Reserve (CFR)*Thermodilution-derived Coronary Flow Reserve (CFR)* = Resting mean transit time / hyperemic mean transit time = Resting mean transit time / hyperemic mean transit time *Pijls NHJ et al.. Circulation 2002;105:2482-2486 Index of Microvascular Resistance (IMR)**:Index of Microvascular Resistance (IMR)**: = Distal coronary pressure x hyperemic mean transit time **Fearon WF. et al.. Circulation. 2003;107:3129-3132 Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp):Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp): = CWP/Pa Thermodilution-derived Coronary Flow Reserve (CFR)*Thermodilution-derived Coronary Flow Reserve (CFR)* = Resting mean transit time / hyperemic mean transit time = Resting mean transit time / hyperemic mean transit time *Pijls NHJ et al.. Circulation 2002;105:2482-2486 Index of Microvascular Resistance (IMR)**:Index of Microvascular Resistance (IMR)**: = Distal coronary pressure x hyperemic mean transit time **Fearon WF. et al.. Circulation. 2003;107:3129-3132 Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp):Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp): = CWP/Pa Guiding cath. Microvasculature Balloon CWP: mm Hg Pa: mm Hg Pressure wire Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

12. Clinical Trial Results. org Primary and Secondary Endpoints Primary Endpoints: All three components of Virchow’s triad (blood constituent, endothelial damage and stasis) exist at extreme levels in the microvasculature of infarcted myocardium.All three components of Virchow’s triad (blood constituent, endothelial damage and stasis) exist at extreme levels in the microvasculature of infarcted myocardium. Coronary flow reserveCoronary flow reserve Index of microvascular resistanceIndex of microvascular resistance Coronary wedge pressureCoronary wedge pressure Collateral flow indexCollateral flow index Coronary diastolic deceleration timeCoronary diastolic deceleration time Secondary Endpoints: Corrected TIMI frame countCorrected TIMI frame count Myocardial blush gradeMyocardial blush grade Infarct sizeInfarct size Changes in left ventricular volumesChanges in left ventricular volumes Major adverse cardiac events (reinfarction, revascularization and death)Major adverse cardiac events (reinfarction, revascularization and death) Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

13. Clinical Trial Results. org Statistical Analysis Calculations were then made of the necessary sample size to detect a 30% difference between the intracoronary streptokinase and control groups for each end point (α=0.05, β=0.20, power=0.80).Calculations were then made of the necessary sample size to detect a 30% difference between the intracoronary streptokinase and control groups for each end point (α=0.05, β=0.20, power=0.80). Group proportions were compared by means of the chi- square test or Fisher exact test, as appropriate. Group means were compared by Student’s t test for independent groups or the Mann-Whitney U test, for variables with normal or non-normal distribution, respectivelyGroup proportions were compared by means of the chi- square test or Fisher exact test, as appropriate. Group means were compared by Student’s t test for independent groups or the Mann-Whitney U test, for variables with normal or non-normal distribution, respectively Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

14. Clinical Trial Results. org Statistical Analysis (cont.) Group means were also adjusted for possible confounding factors (age, pain-to-balloon time, diabetes, hypertension, hyperlipidemia, pre-myocardial infarction angina, slow flow, side branch embolization, smoking and infarct location) using analysis of covariance (ANCOVA).Group means were also adjusted for possible confounding factors (age, pain-to-balloon time, diabetes, hypertension, hyperlipidemia, pre-myocardial infarction angina, slow flow, side branch embolization, smoking and infarct location) using analysis of covariance (ANCOVA). Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

15. Clinical Trial Results. org Study Group Baseline and Demographic Characteristics ICSK Group n = 21 Control Group n = 20 p value (2 tailed) Age (mean, yrs) 51.4± 5.7 52.2±10.90.79 Sex (male) 21190.98 Smoking 17 (81%) 14 (70%) 0.65 Diabetes Mellitus 2 (10%) 3 (16%) 0.65 Hypertension 4 (19%) 7 (37%) 0.20 Dyslipidemia 12 (57%) 14 (74%) 0.27 History of preinfarction angina 5 (24%) 5 (26%) 0.85 Infarct localization Anterior 14 (67%) 16 (80%) 0.54 Non-anterior 7 (33%) 4 (20%) Peak troponin T 9.1 ± 6.5 10.4 ± 7.6 0.61 Initial ST elevation (mean, mm) 15.6 ± 10.5 19 ± 9.7 0.18 Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

16. Clinical Trial Results. org ICSK Group n = 21 Control Group n = 20 p (two tailed) Aspirin 21 (100%) 20 (100%) 1 Beta- Blocker 19 (90%) 18 (90%) 0.96 LMWH 21 (100%) 20 (100%) 1 GP IIb/IIIa inhibitor 21 (100%) 20 (100%) 1 Clopidogrel 21 (100%) 20 (100%) 1 Statins 19 (90%) 18 (90%) 0.96 IV nitroglycerin 16 (76%) 12 (60%) 0.44 ACE inhibitor 19 (90%) 16 (80%) 0.61 Concomitant medications during primary PCI and in the Coronary Care Unit Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

17. Clinical Trial Results. org ICSK group Control group p value Infarct related artery LAD 14 (67%) 16 (80%) 0.54 RCA 6 (28%) 3 (15%) Cx 1 (5%) Number of diseased vessels 1 16 (76%) 14 (70%) 0.73 2 4 (19%) 4 (20%) 3 1 (5%) 2 (10%) Baseline TIMI flow 0/1 (%) 1001001 Pain to balloon time (minute) 257.7 ± 211.8 218.8 ± 109.8 0.93 Angiographic Characteristics Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

18. Clinical Trial Results. org Post-Procedural Results Slow / no-reflow 5 (23%) 2 (10%) 0.41 Side branch embolization 3 (14%) 2 (10%) 1 Max. Inflation pressure (atm) 13.4 ± 3.1 0.29 Number of stents 13.4 ± 3.1 0.71 Mean residual stenosis, % 13.4 ± 3.1 0.59 TIMI flow grades 0 - 1 00 0.41 2 5 (23%) 2 (10%) 3 16 (77%) 18 (90%) Procedural complications 00- Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

19. Clinical Trial Results. org Index of Microvascular Resistance Invasive Microvascular Parameters Two Days after PCI Units p<0.001 n = 21 n = 20 Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

20. Clinical Trial Results. org Coronary Flow Reserve Invasive Microvascular Parameters Two Days after PCI p = 0.002 n = 21 n = 20 Sezer et al, et al. NEJM 2007; 356(18): 1823-1834 Units

21. Clinical Trial Results. org Coronary Wedge Pressures Invasive Microvascular Parameters Two Days after PCI p = 0.04 p < 0.001 mm Hg n = 21 n = 20 Mean Systolic Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

22. Clinical Trial Results. org Invasive Microvascular Parameters Two Days after PCI Pressure Derived Coronary Flow Index Invasive Microvascular Parameters Two Days after PCI p = 0.002 n = 21 n = 20 Sezer et al, et al. NEJM 2007; 356(18): 1823-1834 (Unitless)

23. Clinical Trial Results. org 0.002 0.17 (0.14)-(0.21) 0.17 (0.14)-(0.21) 0.08 (0.05)-(0.11) 0.08 (0.05)-(0.11) <0.001 -0.09 (--­­0.13)-(-0.06) -0.09 (--­­0.13)-(-0.06) 0.17 + 0.07 0.08 + 0.05 CFIp (mean, unitless) <0.001 29.46 (21.80)-(37.12) 29.46 (21.80)-(37.12) 15.17 (8.26)-(22.08) 15.17 (8.26)-(22.08) <0.001 -15.56 (-21.27)-(-9.85) -15.56 (-21.27)-(-9.85) 33.80 + 11.0 18.24 + 6.07 CWP, systolic (mmHg) 0.04 12.54 (6.83)-(18.24) 12.54 (6.83)-(18.24) 7.98 (2.84)-(13.12) 7.98 (2.84)-(13.12) 0.004 -6.39 (-10.73)-(-2.05) -6.39 (-10.73)-(-2.05) 17.20 + 7.93 10.81 + 5.46 CWP, mean (mmHg) 0.002 1.66 (1.25)-(2.07) 1.66 (1.25)-(2.07) 2.29 (1.92)-(2.66) 2.29 (1.92)-(2.66) <0.001 0.62 (0.35)-(0.93) 0.62 (0.35)-(0.93) 1.39 + 0.31 2.01 + 0.57 CFR <0.001 29.05 (22.17)-(35.92) 29.05 (22.17)-(35.92) 11.73 (5.53)-(17.92) 11.73 (5.53)-(17.92) <0.001 -16.20 (-21.75)(10.64) -16.20 (-21.75)(10.64) 32.49 +11.04 16.29 + 5.06 IMR (U) p p Control Group, Mean (95% CI) Control Group, Mean (95% CI) Intracoronary Streptokinase Group, Mean (95% CI) Intracoronary Streptokinase Group, Mean (95% CI) p p Mean Difference 95% CI Control Group n:20 Control Group n:20 Intracoronary Streptokinase Group n:21 Intracoronary Streptokinase Group n:21 Multivariate Univariate Intracoronary Hemodynamic Indices of Microvascular Perfusion Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

24. Clinical Trial Results. org Corrected TIMI Frame Count Relatively Less Invasive Microvascular Parameters p = 0.80p = 0.001p = 0.023 p = 0.80 p = 0.001 p = 0.023 Frame/second n = 21 n = 20 n = 19 n = 18 Immediately after PCI Two days after PCI 6 months after PCI Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

25. Clinical Trial Results. org Diastolic Deceleration Time (in LAD pts) Non-Invasive Microvascular Parameters Two Days after PCI p = 0.001 n = 21 n = 20 milliseconds Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

26. Clinical Trial Results. org ST Segment Resolution p = 0.45 p = 0.39 % n = 21 n = 20 Immediately after PCI 60 minutes after PCI Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

27. Clinical Trial Results. org Angiographic (cTFC, MBG), Electrocardiographic (STR) and Echocardiographic (DDT) Indices of Microvascular Perfusion 0.001 257 (-65)-(580) 257 (-65)-(580) 750 (446)-(1054) 750 (446)-(1054) <0.001 468 (261)-(676) 468 (261)-(676) 360+292 828+258 DDT in the LAD artery (milliseconds) # - - - - - - 7 (53.8) 11 (91.7) 2/3 0.13 - - - - 0.035 - - 6 (46.2) 1 (8.3) 0/1 Six months after primary PCI - - - - - - 6 (32%) 15 (71%) 2/3 0.065 - - - - 0.012 - - 13 (68%) 6 (29%) 0/1 Two days after primary PCI - - - - - - 5 (28%) 10 (50%) 2/3 0.70 - - - - 0.16 - - 13 (72%) 10 (50%) 0/1 Immediately after primary PCI MBG 0.023 25.89 (18.76)-(33.02) 25.89 (18.76)-(33.02) 18.88 (13.57)-(24.18) 18.88 (13.57)-(24.18) 0.014 -6.2 (-11.00)-(-1.39) -6.2 (-11.00)-(-1.39) 27.62 + 6.46 21.42 + 4.98 Six months after primary PCI 0.001 27.51 (22.03)-(32.99) 27.51 (22.03)-(32.99) 19.10 (14.16)-(24.04) 19.10 (14.16)-(24.04) <0.001 -9.27 (-13.50)-(-5.03) -9.27 (-13.50)-(-5.03) 31.79 + 7.58 22.52 + 5.58 Two days after primary PCI 0.80 29.36 (21.48)-(37.25) 29.36 (21.48)-(37.25) 30.30 (23.14)-(37.46) 30.30 (23.14)-(37.46) 0.69 -0.79 (-6.66)-(5.08) -0.79 (-6.66)-(5.08) 34.44 + 8.26 33.6 + 9.45 Immediately after primary PCI cTFC mean UnivariateMultivariate ICSK group Control Mean diff. p ICSK group Control p Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

28. Clinical Trial Results. org End-Systolic Volumes p = 0.063 p = 0.068 Two days after PCI 6 months after PCI n = 21 n = 20 n = 19 n = 18 ml Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

29. Clinical Trial Results. org End-Diastolic Volumes p = 0.5 p = 0.089 Two days after PCI 6 months after PCI ml Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

30. Clinical Trial Results. org LV Ejection Fraction p = 0.078 p = 0.24 Two days after PCI 6 months after PCI % Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

31. Clinical Trial Results. org Infarct Size Six Months after PCI p = 0.17 n = 18 Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

32. Clinical Trial Results. org 0.17 37.28 (21.57-52.99) 37.28 (21.57-52.99) 27.84 (14.35-41.32) 27.84 (14.35-41.32) 0.005 37.05 + 13.84 (n: 18) 37.05 + 13.84 (n: 18) 23 + 13.37 (n: 18) 23 + 13.37 (n: 18) Infarct size %, SPECT 0.82 2.71 (-37.75)-(43.16) 2.71 (-37.75)-(43.16) 5.97 (-27.32)-(39.26) 5.97 (-27.32)-(39.26) 0.24 3.46 + 19.02 14.37 + 31.14 Change in LVEF, % 0.24 51.56 (36.90-66.23) 51.56 (36.90-66.23) 57.68 (45.88-69.47) 57.68 (45.88-69.47) 0.020 46.19 + 12.21 (n: 15) 46.19 + 12.21 (n: 15) 56.18 + 10.69 (n: 17) 56.18 + 10.69 (n: 17) Six months after primary PCI 0.078 47.96 (39.86-56.06) 47.96 (39.86-56.06) 54.25 (46.95-61.55) 54.25 (46.95-61.55) 0.06 44.51 + 12.40 (n: 20) 44.51 + 12.40 (n: 20) 51.52 + 10.76 (n: 21) 51.52 + 10.76 (n: 21) Two days after primary PCI LVEF % 0.036 14.97 (-18.31)- (48.24) 14.97 (-18.31)- (48.24) -11.19 (-37.95)-(15.58) -11.19 (-37.95)-(15.58) 0.04 11.90 + 23.50 (n: 15) 11.90 + 23.50 (n: 15) -4.60 + 22.01 (n: 17) -4.60 + 22.01 (n: 17) Change in EDV, % 0.089 118.77 (76.98-160.56) 118.77 (76.98-160.56) 92.72 (59.11-126.33) 92.72 (59.11-126.33) 0.021 150.13 + 49.28 (n: 15) 115.70 + 29.67 (n: 17) Six months after primary PCI 0.50 118.53 (93.35-143.71) 118.53 (93.35-143.71) 111.22 (88.52-133.91) 111.22 (88.52-133.91) 0.07 137.75 + 36.82 (n: 20) 119.88 + 23.36 (n: 21) Two days after primary PCI EDV ml EDV ml 0.055 15.30 (-28.40)- (59.01) 15.30 (-28.40)- (59.01) -12.32 (-47.47)-(-22.83) -12.32 (-47.47)-(-22.83) 0.014 12.67 + 30.75 (n: 15) 12.67 + 30.75 (n: 15) -13.27 + 25.40 (n: 17) Change in ESV % 0.068 58.68 (25.10-92.27) 58.68 (25.10-92.27) 36.08 (9.07-63.10) 36.08 (9.07-63.10) 0.004 83.73 + 39.32 (n: 15) 83.73 + 39.32 (n: 15) 50.64 + 18.23 (n: 17) 50.64 + 18.23 (n: 17) Six months after primary PCI 0.063 65.03 (47.76-82.30) 65.03 (47.76-82.30) 50.81 (31.25-66.37) 50.81 (31.25-66.37) 0.013 78.65 + 30.55 (n: 20) 78.65 + 30.55 (n: 20) 58.16 + 17.02 (n: 21) 58.16 + 17.02 (n: 21) Two days after primary PCI ESV ml ESV ml p (two tailed) p (two tailed) Control, mean 95%CI Control, mean 95%CI ICSK (+), mean, 95%CI p (two tailed) p (two tailed) Control ICSK (+) Univariate Multivariate Left Ventricular End Systolic (ESV) and End Diastolic Volumes (EDV), Ejection Fraction (LVEF) and Infarct Size (%) Comparisons Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

33. Clinical Trial Results. org Comments and Conclusions Early phase results: In this pilot trial, low dose intracoronary streptokinase administration immediately following primary PCI was compared with standard primary PCI without use of intracoronary streptokinaseIn this pilot trial, low dose intracoronary streptokinase administration immediately following primary PCI was compared with standard primary PCI without use of intracoronary streptokinase Almost all indices of microvascular perfusion concordantly pointed out that use of intracoronary streptokinase immediately after primary PCI yields better perfusion at the microvascular levelAlmost all indices of microvascular perfusion concordantly pointed out that use of intracoronary streptokinase immediately after primary PCI yields better perfusion at the microvascular level Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

34. Clinical Trial Results. org Comments and Conclusions (Cont.) Late term results: At six months, there was no significant difference between the two study groups with regards to left ventricular size of function and infarct size, although there were some trends favoring the streptokinase group.At six months, there was no significant difference between the two study groups with regards to left ventricular size of function and infarct size, although there were some trends favoring the streptokinase group. The trial was not originally planned to be large enough to detect differences in long-term outcome, and indeed enrollment was terminated early based on the midterm data on microvascular perfusion.The trial was not originally planned to be large enough to detect differences in long-term outcome, and indeed enrollment was terminated early based on the midterm data on microvascular perfusion. Since trends in favor of the intracoronary streptokinase group were detected, it is possible that the study was underpowered for these analyses.Since trends in favor of the intracoronary streptokinase group were detected, it is possible that the study was underpowered for these analyses. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834

35. Clinical Trial Results. org Comments and Conclusions (Cont.) The finding of the current study supports the in situ formed (autochthonous) microvascular thrombus hypothesis and pointed out that this thrombus should be taken into consideration for achieving more efficient reperfusion at microvascular level during primary PCI.The finding of the current study supports the in situ formed (autochthonous) microvascular thrombus hypothesis and pointed out that this thrombus should be taken into consideration for achieving more efficient reperfusion at microvascular level during primary PCI. The results of the study should be confirmed by a larger randomized study before applying this treatment modality in daily cardiology practice.The results of the study should be confirmed by a larger randomized study before applying this treatment modality in daily cardiology practice. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834