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Statin: The Good,
the Bad, and the
Unknown
DR. MOHAMMAD SAMIR AZAM SUNNY
DEPARTMENT OF CARDIAC SURGERY, BSMMU
What is statin?
 Statins (or HMG-CoA reductase inhibitors) are a
class of drugs used to lower cholesterol levels by
inhib...
History
 In 1971, Akira Endo, a Japanese biochemist working for the pharmaceutical
company Sankyo, began the search for a...
Statins Classification
 Source
Natural: pravastatin, simvastatin, lovastatin
Synthetic: atorvastatin, fluvastatin
 Solub...
Available forms
Statin Derivation
Atorvastatin Synthetic
Cerivastatin Synthetic
Fluvastatin Synthetic
Lovastatin Mushroom
...
Cholesterol
 Cholesterol transported by lipoprotein.
 Low density lipoprotein: LDL transport cholesterol through out the...
Who will be prescribed for Statin?
 Guidelines by the American College of Cardiology and the American
Heart Association r...
Statin therapy is generally a life long treatment. Discontinuation of statins is
followed within few weeks by a rise in LD...
Dosages
The bad
 Cognitive Effects: statins and memory loss (including reports of
transient global amnesia), forgetfulness and co...
Initiation and Monitoring of Statin Therapy
 Evaluate muscle symptoms and CK before starting therapy
 Evaluate muscle sy...
Drug interactions
 Combining any statin with a fibrate or niacin, another category of
lipid-lowering drugs, increases the...
ACCF/AHA Guideline for Coronary
Artery Bypass Graft Surgery
 Management of Hyperlipidemia: Recommendations
Class I
 1All...
Which is the Best statin for the postoperative coronary artery
bypass graft patient?
 Statin Therapy Prior to CABG Surger...
Statin: Role over RSVG
 Statin therapy to achieve LDL levels less than 100 mg/dL was
independently associated with improv...
The ultimate
 Venous graft patency increases almost double if
20 mg atorvastatin / 10 mg Rusovastatin
continuously taken ...
In pipeline
 New cholesterol lowering drugs being developed
 Gladridin- found in the root of licorice and anise plant
 ...
THANK YOU
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Statin

  1. 1. Statin: The Good, the Bad, and the Unknown DR. MOHAMMAD SAMIR AZAM SUNNY DEPARTMENT OF CARDIAC SURGERY, BSMMU
  2. 2. What is statin?  Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver, which produces about 70 percent of total cholesterol in the body.
  3. 3. History  In 1971, Akira Endo, a Japanese biochemist working for the pharmaceutical company Sankyo, began the search for a cholesterol-lowering drug. Research had already shown cholesterol is mostly manufactured by the body in the liver using the enzyme.  Joseph Goldstein, who won the Nobel Prize for related work on cholesterol, said of Endo: "The millions of people whose lives will be extended through statin therapy owe it all to Akira Endo. The oyster mushroom, naturally contains lovastatin. Aspergillus terreus
  4. 4. Statins Classification  Source Natural: pravastatin, simvastatin, lovastatin Synthetic: atorvastatin, fluvastatin  Solubility Lipophilic: simvastatin, atorvastatin, fluvastatin Hydrophilic: pravastatin, rosuvastatin
  5. 5. Available forms Statin Derivation Atorvastatin Synthetic Cerivastatin Synthetic Fluvastatin Synthetic Lovastatin Mushroom Mevastatin Pitavastatin Yeast Synthetic Pravastatin bacteria Rosuvastatin Synthetic Simvastatin Aspergillus terreus Simvastatin+Ezetimibe Lovastatin+Niacin Atorvastatin+Amlodipine Simvastatin+Niacin
  6. 6. Cholesterol  Cholesterol transported by lipoprotein.  Low density lipoprotein: LDL transport cholesterol through out the body  High density lipoprotein: HDL removes excess cholesterol and carries it back liver for degradation.
  7. 7. Who will be prescribed for Statin?  Guidelines by the American College of Cardiology and the American Heart Association recommend statin treatment for primary prevention of cardiovascular disease in adults with LDL cholesterol > 190 mg/dL.  On average, statins can lower LDL cholesterol by 1.8 mmol/l (70 mg/dl), which translates into an estimated 60% decrease in the number of cardiac events (heart attack, sudden cardiac death) and a 17% reduced risk of stroke after long-term treatment. They have less effect than the fibrates or niacin in reducing triglycerides and raising HDL- cholesterol ("good cholesterol").  In children - familial hypercholesterolemia.  A recent meta-analysis of randomized controlled trials found that statins could reduce the risk of contrast-induced nephropathy by 53% in people undergoing coronary angiography/percutaneous interventions.
  8. 8. Statin therapy is generally a life long treatment. Discontinuation of statins is followed within few weeks by a rise in LDL-C to pretreatment levels Remember….
  9. 9. Dosages
  10. 10. The bad  Cognitive Effects: statins and memory loss (including reports of transient global amnesia), forgetfulness and confusion.  Muscle pain: Coenzyme Q10 (ubiquinone) levels are decreased in statin use. CoQ10 supplements are sometimes used to treat statin- associated myopathy. Hydrophilic statins, such as fluvastatin, rosuvastatin, and pravastatin, are less toxic than lipophilic statins, such as atorvastatin, lovastatin, and simvastatin. Lowest with pravastatin and fluvastatin, probably because they are more hydrophilic and as a result have less muscle penetration.  Diabetes
  11. 11. Initiation and Monitoring of Statin Therapy  Evaluate muscle symptoms and CK before starting therapy  Evaluate muscle symptoms 6 to 12 weeks after starting therapy and at each follow-up visit  If there is no CK elevation or if the CK value is < 3 times the upper limit of normal, statin use can continue with careful monitoring  Discontinuation of statin treatment is mandatory for CK elevations >10 times the upper limit of normal
  12. 12. Drug interactions  Combining any statin with a fibrate or niacin, another category of lipid-lowering drugs, increases the risks for rhabdomyolysis to almost 6.0 per 10,000 person-years(Graham et all "Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs". JAMA 292 (21): 2585–90)  Warfarin: Atorvastatin has not been reported to interact with warfarin. warfarin-simvastatin interaction repoted( Ann Pharmacother. 2007 Jul;41(7):1292-5)  Consumption of grapefruit or grapefruit juice (Mayo clinic: article on interference between grapefruit and medication)
  13. 13. ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery  Management of Hyperlipidemia: Recommendations Class I  1All patients undergoing CABG should receive statin therapy, unless contraindicated (Level of Evidence: A)  2In patients undergoing CABG, an adequate dose of statin should be used to reduce LDL cholesterol to less than 100 mg/dL and to achieve at least a 30% lowering of LDL cholesterol . (Level of Evidence: C) Class IIa  1In patients undergoing CABG, it is reasonable to treat with statin therapy to lower the LDL cholesterol to less than 70 mg/dL in very high-risk⁎  ⁎ ⁎Presence of established cardiovascular disease plus 1) multiple major risk factors (especially diabetes), 2) severe and poorly controlled risk factors (especially continued cigarette smoking), 3) multiple risk factors of the metabolic syndrome (especially high triglycerides ≥200 mg/dL plus non–high-density lipoprotein cholesterol ≥130 mg/dL with low high-density lipoprotein cholesterol [<40 mg/dL]), and 4) acute coronary syndromes. patients undergoing urgent or emergency CABG who are not taking a statin, it is reasonable to initiate high-dose statin therapy immediately (564). (Level of Evidence: C) Class III: Harm  Discontinuation of statin or other dyslipidemic therapy is not recommended before or after CABG in patients without adverse reactions to therapy . (Level of Evidence: B)
  14. 14. Which is the Best statin for the postoperative coronary artery bypass graft patient?  Statin Therapy Prior to CABG Surgery May Improve Outcomes (circulation 2008)  Statin therapy initiated in the early months after hospital discharge independently reduces all-cause mortality and major adverse cardiovascular events after CABG(socity of thoracic surgeon 2012)  Rosuvastatin’s superiority over other statins in allowing patients to reach LDL-C targets has been maintained in ‘real-world’ observational studies. Rosuvastatin has also been shown to increase high-density lipid cholesterol (HDL-C) by greater proportions in comparison with other statins, providing increased anti-atherogenic effects. (oxford journal vol 36)
  15. 15. Statin: Role over RSVG  Statin therapy to achieve LDL levels less than 100 mg/dL was independently associated with improved graft patency in the CASCADE trial( Ann Thorac Surg. 2011 Oct;92(4):1284-90)  Statin therapy is associated with improved graft patency after infrainguinal bypass grafting with saphenous vein(J Vasc Surg. 2004 Jun;39(6):1178-85)  Use of statin causes Patency of Vein Grafts in the Modern Era (RAPS study Canada) SVG patency 80% @7yrs(J Am Coll Cardiol 2012:60;28-35)  Effect of STATINS , LDL 1yr results Patency of Vein Grafts in the Modern Era LDL<100mg/dl SVG patency 96% ; Less intimal hyperplasia when LDL<100mg/dl(kullic et al Ann Thorac Surg 2011:92;1284)
  16. 16. The ultimate  Venous graft patency increases almost double if 20 mg atorvastatin / 10 mg Rusovastatin continuously taken after CABG maintaining LDL level <100mg/dl. (Canadian society of cardiology, over 1000 patient, 2014)
  17. 17. In pipeline  New cholesterol lowering drugs being developed  Gladridin- found in the root of licorice and anise plant  Appears to inhibit oxidation of LDL cholesterol, which is a factor in the build up of arterial plaque.
  18. 18. THANK YOU

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