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
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