1. efficacy of high dose atorvaSTATIN loading before primary percutaneous coronary intervention in ST Elevation Myocardial Infarction (STATIN STEMI) Jung-Sun Kim, MD, PhD*, Jaedeok Kim, MD*, Chan Joo Lee, MD*, Donghoon Choi, MD, PhD*, Byung-Ho Lee, MD*, Sang Hak Lee, MD, Ph D*, Young-Guk Ko, MD*, Jong-Won Ha, MD, Ph D*, Myeong-Ki Hong, MD, Ph D*, Yangsoo Jang, MD, PhD, FACC*, Byoung-Keuk Kim MD, Ph D†, Seong Jin Oh MD†, Dong Woon Jeon MD†, Joo-Young Yang MD†, Jung Rae Cho, MD‡, Jae-Hun Jung, MD‡, Nam-Ho Lee, MD, Ph D‡, Yun-Hyeong Cho, MD§, Deok-Kyu Cho, MD, Ph D§ *Division of Cardiology, Yonsei Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea †Division of Cardiology, Kangnam Sacred Heart Hospital, Seoul, Korea ‡Division of Cardiology, NHIC Ilsan Hospital, Koyang, Korea §Division of Cardiology, Department of Internal Medicine, Myongji Hospital, Kwandong University College of Medicine, Goyang, Korea

2. The effects of prior use of atorvastatin on coronary blood flow after primary percutaneous coronary intervention in patients presenting with acute myocardial infarction Celik T, et al. Coronary Artery Disease 2005 Only mean TIMI frame count was detected to be significantly lower in patients taking at least 40mg. Atorvastatin for at least 6 months compared with that of the patients taking no statin (p < 0.001). After confounding variables were controlled for, the mean TIMI frame count of patients in group 2 was significantly lower than that of the patients in group 1 (p = 0.001). Backgrounds

3. Although statin prior to PCI has favorable effects in stable angina and ACS except ST elevation MI (STEMI), there have have been few studies for STEMI. Celik T et al. reported in patients with STEMI that prior statin use may improve coronary blood flow after PCI in patients with AMI. But this study was retrospective, nonrandomized study and evaluated the effects for chronic statin therapy no acute high dose effect. The effects of prior use of atorvastatin on coronary blood flow after primary percutaneous coronary intervention in patients presenting with acute myocardial infarction

4. Hypothesis We investigate whether acute high-dose statin prior to primary PCI can have beneficial effect or not for periprocedural period and 30 days-cardiac events.

5. Study Design

6. Inclusion Criteria The patient must be at least 18-80 years of age. The patient had the symptoms of acute myocardial infaction within 12 hours with ST segment elevation of more than 1 mm in at least two contiguous leads of EKG or new onset LBBB. The patient or guardian agrees to the study protocol a nd provides informed, written consent.

7. Patients with any of the following will be excluded from participation: Patients to whom PCI can not be undergone within 12 hours from receiving the study drug Cardiogenic shock or symptomatic hypotension or sitting SBP < 95 mmHg The history of major surgery, trauma, retinal hemorrhage, significant gastrointestinal or genitourinary bleeding within recent 6 weeks; history of cerebrovascular attack within two years, or cerebrovascular attack with a significant residual neurological deficit Severe or malignant hypertension (= sitting SBP > 180 mmHg and/or sitting DBP > 105 mmHg) The history or diagnosis of vasculitis; renal insuffiency (the level of serum creatinine is two times higher than the upper limit of normal of each center) The patients who might die of other disease than cardiac disease during the trial. Exclusion Criteria

8. Primary End-Point To evaluate the effect of high-dose Atorvastatin (started at emergency room) in STEMI –30 Days MACE (Death, non-fatal MI, TVR)

9. Secondary End-Point - Corrected TIMI frame count - Myocardial blush grade after PCI - ST resolution at 90 minutes - MACE at 9 months

10. BASELINE CLINCAL CHARACTERISTICS Atorvastatin 80 mg (n = 86) Atorvastatin 10 mg (n = 85 ) P-value Age (years)61 ± 1159 ± 110.99 Gender (M:F)66 : 2066 : 190.89 Diabetes mellitus21 (24.5%)16 (18.9%)0.47 Hypertension45 (52.3%)39 (46.4%)0.45 Hypercholesterolemia34 (39.5%)32 (38.1%)0.88 Current smoker35 (40.7%)43 (50.6%)0.38 Renal insufficiency8 (9.3 %)3 (3.5 %)0.12 Previous MI2 (2.3 %)2 (2.4 %)1.00 Previous PCI5 (5.8%)6 (7.1%)0.74 Pain to balloon time (min)231 ± 167241 ± 1580.56 Door to balloon time (min)76 ± 4477 ± 390.40 IABP use13 (15.1%)12 (14.1%)1.00 LVEF (%)46 ± 1147 ± 110.64

11. Baseline periprocedural findings Atorvastatin 80 mg (n = 86) Atorvastatin 10 mg (n = 85 ) P-value Culprit lesion Lt. main0 (0%)3 (1.8%)0.24 LAD47 (54.7%)51 (60%) LCx22 (25.6%)16 (18.8%) RCA17 (19.8%)15 (17.6%) Multi-vessel disease59 (68.6 %)45 (52.9 %)0.04 Lesion type B2/C83 (96.5%)76 (89.5%)0.15 TIMI grade 0 before PCI41 (48.2%)45 (52.9%)0.66 Intracoronary thrombus56 (65.1%)57 (67.1%)0.87 Bifurcation14 (16.3%)16 (19.9%)0.62 GP IIb/IIIa inhibitor20 (23.5%)17 (20.0 %)0.71 IVUS use8 (9.3%)15 (17.6%)0.12

12. Angiographic and eletrocardiographic outcomes after primary PCI Atorvastatin 80 mg (n = 86) Atorvastatin 10 mg (n = 85 ) P-value Type of PCI POBA1 (1.2 %) 0.73 Stent75 (98.8 %)74 (98.8 %)0.73 Type of stent DES78 (90.7 %)74 (87.1 %)0.73 BMS7 (8.1 %)10 (11.8 %)0.73 Stent diameter3.1±0.33.1±0.40.55 Stent length30.1±11.131.3±11.90.19 Group 1: 80 mg Atorvastatin at ER, Group 2: 10 mg Atorvastatin at ER

13. Atorvastatin 80 mg (n = 86) Atorvastatin 10 mg (n = 85 ) P- value Peak CK-MB (ng/dL)239±162239±2270.99 hsCRP (mg/L) at 24 hr after PCI 4.14 ± 7.997.45 ± 22.810.10 TIMI grade 3 after procedure83 (96.5 %)76 (89.4 %)0.07 TIMI blush grade2.2±0.81.9±0.80.02 Corrected TIMI frame count26.7±12.234.1±19.00.01 Mean STR at 90 min61.8±26.250.6±25.80.01 Complete STR at 90 min34 (39.5 %)19 (23.8 %)0.03 Angiographic and eletrocardiographic outcomes after primary PCI Group 1: 80 mg Atorvastatin at ER, Group 2: 10 mg Atorvastatin at ER

14. Incidence of Major Adverse Cardiac Events at 30-Days Follow-up MACE : cardiovascular death, MI and TVR, stent thrombosis Group 1: 80 mg Atorvastatin at ER, Group 2: 10 mg Atorvastatin at ER Atorvastatin 80 mg (n = 86) Atorvastatin 10 mg (n = 85 ) P-value Death0.31 Any cause1 (1.2 %)3 (3.5 %) Cardiovascular0 (0.0 %)3 (3.5 %) Non-fatal MI4 (4.7 %)6 (7.1 %)0.50 Periprocedural MI3 (3.5 %)5 (5.9 %)0.50 TVR0 (0.0 %)1 (1.2 %)0.50 MACE5 (5.8 %)9 (10.6 %)0.26 Acute or subacute ST0 (0.0 %)1 (1.2 %)0.50

15. Kaplan Meier survival curve in STATIN STEMI at 9-months Follow-up.

16. Conclusion The loading of high dose atorvastatin did not decrease the MACE but improve the immediate coronary flow after primary PCI. Therefore, it might be helpful for achieving the optimal results for primary PCI in STEMI through the beneficial effects on microvascular function.