Published on March 17, 2014
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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