AGAINST THE MOTION

1
Should statins be given to all diabetic patients
?

• AGAINST THE MOTION
• Dr Bharti Kalra
• Bharti Hospital
• Karnal Haryana

2
Are all people alike ?

• NO

3
Are all patients alike ?

• NO

4
Can all treatment be alike ?

• NO

5
Can all diabetics be given statins ?

• NO

6
Can we generalize ?

• The defining feature of diabetes is hyperglycemia
• It is not hyperlipidemia
• All diabetics do not receive hypoglycemics
• All hyperlipidemics do not receive statins
• How then, can all diabetics be prescribed statins
  ?

7
HPS limitations

• Age 40 to 80 only
• Child-bearing /Pre-conception women
• Heart failure
• Renal/hepatic failure
• Simvastatin alone (not other statins)
• High dose 40 mg/day

8
HPS

• Non-fasting cholesterol/triglyceride values used
  this overestimates LDL-C by 15
• used Freidewald equation not used Direct LDL-C
  values

9
HPS

• Safety profile was good
• However, patients with side effects during a 4-6
  week run in period of statin therapy had already
  been excluded
• Such good record may not be seen in an unselected
  population

10
HPS

• Effect achieved after 12 months therapy
• Are our patients that patient ?
• The characteristics of the low-LDL subgroup have
  not been reported, i.e, what proportion was
  diabetic
• Efficacy of simvastatin in LDL lt100 group not
  reported

11
OTHER STUDIES

• PROSPER
• pravastatin40 mg
• No reduction in stroke
• New cance 25 increase
• No reduction in disability
• No improvement in cognitive function

• ALLHAT-LLT
• Pravastatin
• No change in all-cause mortality
• No change in CHD event rates, except in
  African-American group

12
Other studies

• PROVE IT
• In patients with LDL lt 125, no difference in risk
  of coronary events between intensive cholesterol
  lowering group and standard care group

• VA-HIT
• Fibrates may be better than statins in diabetic
  patients

13
Side effects

• Adverse effects of statins are many
• Muscle aches
• Rhabdomyolysis
• Renal failure
• Hepatic dysfunction
• Erectile dysfunction
• Many others

14
Myalgias

• Myalgias are common in diabetics
• Statins should be withdrawn if myalgia occurs or
  if CPK rises 3x (Hamilton, 2001)
• In a myalgic patient ? Osteoporosis?
  Neuropathy, can we give a statin ?

15
Low CoQ

• Reduction in coenzyme Q
• Muscular weakness
• Cardiac dysfunction
• Poor quality of life
• Are we trying to improve vascular/cardiac
  function with statins, or are we actually
  worsening it ?

16
Interactions

• Drug interactions are many erythromycin,
  macrolides, cyclosporine
• This becomes more significant in the era of
  polypharmacy
• We may end up ingesting lots of drugs, but not
  absorbing or utilizing any of them
• Risk of myopathy 10x with amiodarone or verapamil
  co-prescription

17
Safety concerns

• Cerivastatin was withdrawn from the market 2
  years ago
• Lovastatin is no longer used
• What is the guarantee that other statins will not
  meet the same fate ?
• Do hydrophilic and lipophilic statins share the
  same therapeutic effects ?

18
Ive forgotten the title

• Amnesia is a common side effect of statin therapy

19
High triglycerides

• Drug of choice gemfibrozil
• HPS least benefits of simvastatin in patients
  with high triglycerides
• This is the commonest abnormality in Indian
  diabetics
• Gemfibrozil has to be added, but this increases
  risk of myopathy

20
Young diabetics

• Statins in paediatric age group
• Statins in reproductive age group
• Statins in undernourished Indian diabetics
• Effect in different ethnic groups

21
Too low a cholesterol

• Increases risk of cerebral haemorrhage (Iso et
  al, 1989)
• Decreases production of cholesterol- dependent
  hormones testosterone, femal sex hormones,
  adrenal steroids
• Disturbs a host of essential chemical reactions
• Increases death (Neaton, 1992 Honolulu Heart
  Program, 1991)

22
Is cholesterol the only risk factor?

• Focus on obesity, CRP, other markers of
  inflammation (TNF-alpha)
• Perhaps statin use should be limited to patients
  with borderline cholesterol and high CRP titres
  only
• Perhaps newer risk factors may emerge, which will
  help us decide when to use statins

23
Other approaches

• Folic acid, cyanocobalamin to reduce homocysteine
  levels
• Aspirin to improve platelet/endothelial function
• Ramipril (HOPE), losartan (LIFE), intensive BP
  control (HOT) to reduce mortality
• Insulin to reduce CRP

24
Other approaches

• Rosiglitazone to improve endothelial function
  (Pistrosch et al, 2004)
• Pioglitazone, metformin to improve lipoprotein
  levels (Lawrence et al, 2004)
• Diet, exercise to improve insulin sensitivity and
  lower cholesterol

25
The final verdictNCEP report Grundy et al,
Circulation 12 July 2004

• Only judicious use of statins can be advocated
• Do not give statins to all your diabetics
• Attempt to achieve LDL lt 70 in diabetics with
  established CVD
• For diabetics without CVD with LDL lt100, use
  clinical judgement
• if LDL 100 130, use statins if patient is high
  risk
• if LDL gt 130, use statins for all

26

• THANK YOU