Statins are a class of drugs that lower cholesterol by inhibiting its production in the liver. They have been shown to significantly reduce risks of cardiovascular events. While generally safe and effective for primary prevention when LDL is over 190 mg/dL, statins can cause side effects like muscle pain and cognitive issues. They work best when started before or after CABG to improve graft patency. Rosuvastatin and atorvastatin may provide the greatest benefits for postoperative CABG patients by allowing LDL to be lowered below 100 mg/dL. Maintaining LDL at this level can nearly double venous graft patency rates.

1. Statin: The Good,
the Bad, and the
Unknown
DR. MOHAMMAD SAMIR AZAM SUNNY
DEPARTMENT OF CARDIAC SURGERY, BSMMU

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. 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. Statins Classification
 Source
Natural: pravastatin, simvastatin, lovastatin
Synthetic: atorvastatin, fluvastatin
 Solubility
Lipophilic: simvastatin, atorvastatin, fluvastatin
Hydrophilic: pravastatin, rosuvastatin

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. 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.

10. 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.

12. 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….

13. Dosages

14. 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

17. 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

18. 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)

19. 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)

20. 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)

21. 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)

22. 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)

23. 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.

24. THANK YOU