efficacy of high dose atorvaefficacy of high dose atorvaSTATINSTATIN loading loading

before primary percutaneous coronary before primary percutaneous coronary

intervention in intervention in ST EST Elevation levation MMyocardial yocardial

IInfarction (STATIN STEMI)nfarction (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

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

• 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

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.

Study Design

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

and provides informed, written consent.

• 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

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)

Secondary End-Point

- Corrected TIMI frame count

- Myocardial blush grade after PCI

- ST resolution at 90 minutes

- MACE at 9 months

BASELINE CLINCAL CHARACTERISTICSAtorvastatin 80 mg

(n = 86)Atorvastatin 10 mg

(n = 85 ) P-value

Age (years) 61 ± 11 59 ± 11 0.99

Gender (M:F) 66 : 20 66 : 19 0.89

Diabetes mellitus 21 (24.5%) 16 (18.9%) 0.47

Hypertension 45 (52.3%) 39 (46.4%) 0.45

Hypercholesterolemia 34 (39.5%) 32 (38.1%) 0.88

Current smoker 35 (40.7%) 43 (50.6%) 0.38

Renal insufficiency 8 (9.3 %) 3 (3.5 %) 0.12

Previous MI 2 (2.3 %) 2 (2.4 %) 1.00

Previous PCI 5 (5.8%) 6 (7.1%) 0.74

Pain to balloon time (min) 231 ± 167 241 ± 158 0.56

Door to balloon time (min) 76 ± 44 77 ± 39 0.40

IABP use 13 (15.1%) 12 (14.1%) 1.00

LVEF (%) 46 ± 11 47 ± 11 0.64

Baseline periprocedural findings

Atorvastatin 80 mg

(n = 86)Atorvastatin 10 mg

(n = 85 )P-value

Culprit lesion

Lt. main 0 (0%) 3 (1.8%) 0.24

LAD 47 (54.7%) 51 (60%)

LCx 22 (25.6%) 16 (18.8%)

RCA 17 (19.8%) 15 (17.6%)

Multi-vessel disease 59 (68.6 %) 45 (52.9 %) 0.04

Lesion type B2/C 83 (96.5%) 76 (89.5%) 0.15

TIMI grade 0 before PCI 41 (48.2%) 45 (52.9%) 0.66

Intracoronary thrombus 56 (65.1%) 57 (67.1%) 0.87

Bifurcation 14 (16.3%) 16 (19.9%) 0.62

GP IIb/IIIa inhibitor 20 (23.5%) 17 (20.0 %) 0.71

IVUS use 8 (9.3%) 15 (17.6%) 0.12

Angiographic and eletrocardiographic outcomes after primary PCI

Atorvastatin 80 mg

(n = 86)

Atorvastatin 10 mg

(n = 85 )P-value

Type of PCI

POBA 1 (1.2 %) 1 (1.2 %) 0.73

Stent 75 (98.8 %) 74 (98.8 %) 0.73

Type of stent

DES 78 (90.7 %) 74 (87.1 %) 0.73

BMS 7 (8.1 %) 10 (11.8 %) 0.73

Stent diameter 3.1±0.3 3.1±0.4 0.55

Stent length 30.1±11.1 31.3±11.9 0.19

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

Peak CK-MB (ng/dL) 239±162 239±227 0.99

hsCRP (mg/L) at 24 hr after PCI

4.14 ± 7.99 7.45 ± 22.81 0.10

TIMI grade 3 after procedure

83 (96.5 %) 76 (89.4 %) 0.07

TIMI blush grade 2.2±0.8 1.9±0.8 0.02

Corrected TIMI frame count 26.7±12.2 34.1±19.0 0.01

Mean STR at 90 min 61.8±26.2 50.6±25.8 0.01

Complete STR at 90 min 34 (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

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

Death 0.31

Any cause 1 (1.2 %) 3 (3.5 %)

Cardiovascular 0 (0.0 %) 3 (3.5 %)

Non-fatal MI 4 (4.7 %) 6 (7.1 %) 0.50

Periprocedural MI 3 (3.5 %) 5 (5.9 %) 0.50

TVR 0 (0.0 %) 1 (1.2 %) 0.50

MACE 5 (5.8 %) 9 (10.6 %) 0.26

Acute or subacute ST 0 (0.0 %) 1 (1.2 %) 0.50

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

ConclusionConclusion

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.