Early Statin Therapy In AMI with Low LDL-

Cholestrol

By Dr. Abdelsalam Sherif

MD CardiologyVenue : Medina CVD Meeting

Crown Plaza Hotel, al –Madinah13 th -14 th March 2014

Introduction

Beneficial Effect of Statins in CVD Early Statin Therapy IN ACS

Statin Therapy IN AMI with Low LDL-cholestrol

Introduction

1. Significant TC and LDL-c lowering efficacy2. Positive impact on other lipoprotein

classes3. Slowing progression/regression of

atherosclerosis4. Reduction in CVD events/mortality5. Good safety profile6. Added value7. Acceptable cost

Properties of a Statin for the 21st Century

Beneficial Effect of Statins in CVD

Inflammation Repair

Unstable plaque

Increased lipidsLipid oxidation

Infection?Genetic susceptibility

Increased lipidsLipid oxidation

Infection?Genetic susceptibility

Lipid-lowering drugs Antioxidants?

Antibiotics?Mechanical injury

Lipid-lowering drugs?Antioxidants

Antibiotics?Mechanical injury

Stable plaque

Modified from Weissberg (1999)

Balancing the stability equation

statins

Endothelial Function

+

Thrombosis-

Plaque Stabilization

+

Inflammmation

-

Pleiotropic effects of statins1.Endothelial Cells : a) + effect on NO b) + effect on endothelial progenitor cells. c) – effect on cyclo- oxygenase . d) – effect on endothelin-1. e) – effect on adhesions molecules.

2. Inflammation : a) – effect on CRP. b) – effect on CD40. c) – effect on adhesion molecules. d)- effect on pro-inflammatory cytokines.

3. Thrombosis: a) – effect on fibrinogen. b) – effect on platelet aggregation. c) – effect on thromboxane- A2. d)- effect on PAI-1. e) + effect on tPA.

Aggressive DLP Management Reduces Risk…the Lower the Better

Adapted from Ballantyne CM et al. Am J Cardiol 1998;82:3Q–12Q.

LDL-C achieved mg/dL (mmol/L)

WOSCOPS - Pl

AFCAPS/TexCAPS - Pl

ASCOT - PlAFCAPS/TexCAPS - Rx

WOSCOPS - Rx

ASCOT - Rx

ALLHAT - RxALLHAT - Pl

4S - Rx

HPS - Pl

LIPID - Rx

4S - Pl

CARE - Rx

LIPID - Pl

PROSPER - PlCARE - Pl

HPS - Rx

PROSPER - Rx

0

5

10

15

20

25

30

70( 1.8) 90( 2.3) 110( 2.8) 130( 3.4) 150( 3.9) 170( 4.4) 190( 5.0) 210( 5.4)

Event

rate

)%(

- Secondary prevention

- Primary prevention

Rx - Statin therapy

Pl - Placebo

Early Statin Therapy IN ACS

Braunwald (1996)

Deaths/100 patients/month

Time (months after hospital admission)

Risk of death in patients with coronary heart disease is greatest

early after an ACS

Acute MIUnstable angina

Stable angina

0

5

10

15

20

25

0 1 2 3 4 5 6

Statins*LDL-C reduction

Reduction inchylomicron and

VLDL remnants,IDL, LDL-C • Restore endothelial

function• Maintain SMC function • Anti-inflammatory

effects• Decreased thrombosis

Lumen

Lipid core

Macrophages

Smooth muscle

cells

Potential mechanisms of benefit of

statins in ACS

*Statins differ significantly in terms of these effects/mechanisms

1 Pravastatin and Thrombolytic Therapy 2 Lipids in Coronary Artery Disease 3 Reduction of Cholesterol in Ischaemia and Function of the Endothelium4 FLuvastatin On RIsk Diminishing after Acute myocardial infarction5 Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering

Clinical evidence for the benefits of early statin initiation

Study Time to Statin Resultsinitiation

PTT1 6 h pravastatin coronary events restenosis rates

L-CAD2 6 d pravastatin Improved outcomes mean progression coronary lesion regression

RECIFE3 10 d pravastatin Rapid improvement of (mean)

endothelial function

FLORIDA4 8 d fluvastatin No significant benefit

MIRACL5 24–96 h atorvastatin time to first event

Survival)%(

Days

100

99

98

97

96

95

94

93

92

0 30 60 90 120 150 180

Log rank 2=87, p<0.001

No lipid-lowering agents (n=6374)

Lipid-lowering agents (n=2141)

Aronow et al (2000)

PURSUIT: Retrospective analysis shows early mortality reduction with

lipid-lowering therapy

Statin Therapy IN AMI with Low LDL-cholestrol

Date of download :3/2/2014

Benefit of Early Statin Therapy in Patients With Acute Myocardial Infarction Who Have Extremely Low Low-Density Lipoprotein

CholesterolJ Am Coll Cardiol. 2011;58(16):1664-1671. doi:10.1016/j.jacc.2011.05.057

Baseline Clinical Characteristics

Date of download :3/2/2014

Procedural Characteristics

Date of download :3/2/2014

Clinical Outcomes at 6 and 12 Months According to Statin Medication

Cumulative Secondary Endpoints at 12 Months According to Statin Medication

Benefit of Early Statin Therapy in Patients With Acute Myocardial Infarction Who Have Extremely Low Low-

Density Lipoprotein CholesterolJ Am Coll Cardiol. 2011;58(16):1664-1671. doi:10.1016/j.jacc.2011.05.057

Estimates of the Rate of the Primary Endpoint EventsThe primary endpoint was the composite of death, recurrent myocardial infarction, and coronary revascularization. MACE = major adverse cardiac event(s); PCI = percutaneous coronary intervention.

Benefit of Early Statin Therapy in Patients With Acute Myocardial Infarction Who Have Extremely Low Low-

Density Lipoprotein Cholesterol

Estimates of Hazard Ratios for the Primary Endpoint in Selected SubgroupsHazard ratios are shown on a logarithmic scale. CI = confidence interval; hs-CRP = high-sensitivity C-reactive protein; NSTEMI = non–ST-segment elevation myocardial infarction; STEMI = ST-segment elevation myocardial infarction.

Several clinical trials with Statins have indicated the benefits of early treatment in ACS

Effects beyond lipid lowering may contribute to the early benefit

Statin therapy in patients with AMI with LDL-C level below 70 mg/dl was associated with improved clinical outcome.

Conclusions