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Role of atorvastatin


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Role of atorvastatin

  1. 1. Saini NK et al Source Journal: Inventi Rapid: Pharmacy Practice Vol.2011, Issue 2
  2. 2. Introduction  C-reactive protein plays a role in the expression of different adhesion molecules on endothelial cells and the protein is able to activate human complement within the plaque.  It has been proven that an elevated CRP level is associated with an increased risk of occlusive arterial disease.
  3. 3. C-Reactive protein  C-reactive protein is an acute phase protein, the levels of which rise in response to inflammation, microbial infection.  CRP serves as a critical component of the innate immune system by enhancing the uptake of microbes by phagocytic cells of the immune system.
  4. 4. Normal CRP levels  C-Reactive protein normal: 0-1.0mg/dl (or) 10mg/L (SI Units)  The hs-CRP test measures the risk for cardiovascular problems. It may be done to find out an increased chance of having a sudden heart problem, such as a heart attack. High-sensitivity C-reactive protein (hs-CRP) levels Less than 1.0mg/L Lowest risk 1.0-3.0mg/L Average risk More than 3.0mg/L Highest risk
  5. 5. Atorvastatin  Atorvastatin is a synthetic HMG-CoA reductase inhibitor with a great potency to lower both cholesterol and triglyceride concentrations.  Controlled studies with various groups of hyperlipidemic patients showed reduction of LDL cholesterol by up to 60% and triglyceride by up to 50%.  Mechanism of action:  Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate limiting enzyme in cholesterol synthesis.
  6. 6. Mechanism of action of Atorvastatin
  7. 7. Pleiotropy of statins  Statins have been shown to decrease ROS production and VSMC proliferation, enhances eNOS levels exhibit anti-thrombotic and anti-inflammatory effects thereby, attenuate artherosclerotic plaques.  Trials using different statins, including pravastatin, simvastatin and atorvastatin have all demonstrated favourable reductions in C-reactive protein level. VSMC-Vascular Smooth Muscle Cell
  8. 8. Role of Atorvastatin on CRP level  Atorvastatin improves endothelium dependent vasodilatation and a lowering of plasma CRP concentrations.  It has been demonstrated that statins have an effect on markers of inflammation, particularly C-reactive protein, independent of their lipid lowering effect.  Novel route of plaque attenuation: Artherosclerotic plaque growth may be attenuated with therapy aimed at minimizing inflammation.
  9. 9. Artherosclerotic plaque attenuatuion through CRP level reduction  Increased levels of C-reactive protein have associated with arterial wall inflammation.  Thus reduction in CRP levels may reduce the extent of endothelial-cell opsonisation, macrophage recruitment and blunting of nitric oxide release.  Prevention of vasoconstriction by attenuating the pro- inflammatory process and preserving vasodilatation may allow sufficient perfusion to prevent myocardial ischemia.
  10. 10. Suppression of expression of inflammatory parameters by Atorvastatin Reduction in C-reactive protein level. Reduction of endothelial cell opsonisation. Increase in nitric oxide release Vasodilation
  11. 11. Vasodilation Increase in perfusion Sufficient blood supply to the cardiac tissue in need Prevention of myocardial ischemia
  12. 12. Clinical trials Name of the study Type Drug % Reduction in CRP level MIRACL Randomized controlled trial Atorvastatin 83% CURVES Comparative dose efficacy study Pravastatin, Simvastatin, Atorvastatin Significant TexCAPS Randomized placebo controlled trial Lovastatin 14.8% PRINCE trial Antiinflammatory effects Pravastatin 16.9% REVERSAL Atorvastatin Pravastatin 36.4% 5.2%
  13. 13. Inference  The use of statins may prevent ischemia by both inhibiting deposition of lipids and decreasing inflammation.  Atorvastatin also lowers plasma LDL cholesterol and C-reactive protein in type-2 diabetic patients, therefore could be a useful medication for the prevention of cardiovascular diseases in diabetic patients.
  14. 14. Doses of commonly used statins Statin Dose Brand name Manufacturer Lovastatin 10mg, 20mg ROVACOR, AZTATIN, LOVAMEG Ranbaxy, Sun Pharma Simvastatin 5mg, 10mg, 20mg SIMVOTIN, SIMCARD Ranbaxy (Stancare) Pravastatin 10mg, 20mg PRAVATOR Ranbaxy(Solus) Atorvastatin 5mg, 10mg, 20mg AZTOR, ATORVA, ATORLIP, LIPITOR Zydus Cadilla, Pfizer. Rosuvastatin 5mg, 10mg, 20mg ROSUVAS, ROSYN Ranbaxy
  15. 15. Thank you!!!