Effect of statin therapy on dyslipidemia is well known, and the beneficial efficacy of statin therapy in primary and secondary prevention of cardiovascular events was docmented in a lot of RCTs. Mant studies recomended the statin therapy earlier in ACS, and what about the effect of statin in situation of AMI patients with low LDL- cholestrol.

1. By
Dr. Abdelsalam Sherif
MD Cardiology
Venue : Medina CVD Meeting
Crown Plaza Hotel, al –Madinah
13 th -14 th March 2014

6. 1. Significant TC and LDL-c lowering efficacy
2. Positive impact on other lipoprotein classes
3. Slowing progression/regression of
atherosclerosis
4. Reduction in CVD events/mortality
5. Good safety profile
6. Added value
7. Acceptable cost

10. Inflammation Repair
Unstable plaque
Increased lipids
Lipid oxidation
Infection?
Genetic susceptibility
Lipid-lowering drugs
Antioxidants?
Antibiotics?
Mechanical injury
Stable plaque
Modified from Weissberg (1999)

11. statins
Endothelial
Function
+
Thrombosis
-
Plaque
Stabilization
+
Inflammmation
-

12. 1.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.

14. 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 - Rx
ALLHAT - Pl
4S - Rx
HPS - Pl
LIPID - Rx
4S - Pl
CARE - Rx
LIPID - Pl
PROSPER - Pl
CARE - 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)
Eventrate(%)
- Secondary prevention
- Primary prevention
Rx - Statin therapy
Pl - Placebo

17. Braunwald (1996)
Deaths/100 patients/month
Time (months after hospital admission)
Acute MI
Unstable angina
Stable angina
0
5
10
15
20
25
0 1 2 3 4 5 6

19. Statins*LDL-C reduction
Reduction in
chylomicron and
VLDL remnants,
IDL, LDL-C • Restore endothelial
function
• Maintain SMC function
• Anti-inflammatory effects
• Decreased thrombosis
Lumen
Lipid
core
Macrophages
Smooth
muscle
cells
*Statins differ
significantly
in terms of these
effects/mechanisms

21. 1 Pravastatin and Thrombolytic Therapy
2 Lipids in Coronary Artery Disease
3 Reduction of Cholesterol in Ischaemia and Function of the Endothelium
4 FLuvastatin On RIsk Diminishing after Acute myocardial infarction
5 Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering
Study Time to Statin Results
initiation
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

24. Survival (%)
Days
100
99
98
97
96
95
94
93
92
030 60 90120150180
Log rank 2=87, p<0.001
No lipid-lowering agents (n=6374)
Lipid-lowering agents (n=2141)
Aronow et al (2000)

28. Date of download:
3/2/2014
J Am Coll Cardiol. 2011;58(16):1664-1671. doi:10.1016/j.jacc.2011.05.057
Baseline Clinical Characteristics

29. Date of download:
3/2/2014

30. Date of download:
3/2/2014

32. J Am Coll Cardiol. 2011;58(16):1664-1671. doi:10.1016/j.jacc.2011.05.057
Estimates of the Rate of the Primary Endpoint Events
The primary endpoint was the composite of death, recurrent myocardial infarction, and coronary revascularization. MACE =
major adverse cardiac event(s); PCI = percutaneous coronary intervention.

33. Estimates of Hazard Ratios for the Primary Endpoint in Selected Subgroups
Hazard 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.

34.  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.