Early statin therapy in Acute myocardial Infarction with low LDL- cholestrol

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Health & Medicine

Published on March 17, 2014

Author: abusherif60

Source: slideshare.net

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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.

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

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

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

statins Endothelial Function + Thrombosis - Plaque Stabilization + Inflammmation -

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.

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

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

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

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

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)

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

Date of download: 3/2/2014

Date of download: 3/2/2014

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.

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.

 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.

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