Cholesterol and Lipids

Cholesterol and LipidsCholesterol and Lipids

TIPSTIPS

Wokefield Park 15/5/2013Wokefield Park 15/5/2013

Just a few questions!Just a few questions!

What is the NDA target for total cholesterol and What is the NDA target for total cholesterol and LDL cholesterol?LDL cholesterol?

What are the QOF targets for cholesterol?What are the QOF targets for cholesterol? What is the ideal time to take a statin and why?What is the ideal time to take a statin and why? Name the most serious side effect of statins. Name the most serious side effect of statins. What blood test would you order if you suspected What blood test would you order if you suspected

it?it? Name another side effect of statins.Name another side effect of statins. All statins increase HDL cholesterol – true or false?All statins increase HDL cholesterol – true or false? What is the most typical lipid profile for type 2 What is the most typical lipid profile for type 2

diabetes?diabetes? What is the most typical lipid profile for type 1 What is the most typical lipid profile for type 1

diabetes?diabetes?

R77 Statins & EzetimibeR77 Statins & Ezetimibe

For a person who is 40 yrs+For a person who is 40 yrs+

• Simvastatin (to 40 mg) unless CVS Simvastatin (to 40 mg) unless CVS risk from non-hyperglycaemia-risk from non-hyperglycaemia-related factors is low (see R72)related factors is low (see R72)

R72 Consider a person to be at R72 Consider a person to be at high CVS risk unless……high CVS risk unless……

• Not overweightNot overweight

• NormotensiveNormotensive

• No microalbuminuriaNo microalbuminuria

• Non-smokerNon-smoker

• No high risk lipid profileNo high risk lipid profile

• No h/o CVS diseaseNo h/o CVS disease

• No FH of CVS diseaseNo FH of CVS disease

If low CVS risk…………If low CVS risk…………

• Assess CVS risk using UKPDS risk Assess CVS risk using UKPDS risk engineengine

• Start simvastatin if CVS risk > 20% Start simvastatin if CVS risk > 20% over 10 yrsover 10 yrs

Once on a statin………..Once on a statin………..

• Repeat lipid profile in 1-3 months Repeat lipid profile in 1-3 months then annuallythen annually

• If total cholesterol>4.0 or LDL If total cholesterol>4.0 or LDL cholesterol >2.0 mmol/L titrate cholesterol >2.0 mmol/L titrate simvastatin to 80 mg dailysimvastatin to 80 mg daily

Consider intensifying if…….Consider intensifying if…….

• Existing/newly diagnosed CVS Existing/newly diagnosed CVS diseasedisease

• Choose different statin/ezetimibeChoose different statin/ezetimibe

If h/o raised If h/o raised triglycerides…….triglycerides…….

• Consider secondary causesConsider secondary causes

• Full lipid profileFull lipid profile

• Prescribe fenofibrate if Tg remain > Prescribe fenofibrate if Tg remain > 4.5 mmol/L4.5 mmol/L

• If Tg remain > 2.3 mmol/L consider If Tg remain > 2.3 mmol/L consider adding fenofibrate to statinadding fenofibrate to statin

Kaplan–Meier Estimates of the Incidence of Outcome Events in the Total Study Population.

Estruch R et al. N Engl J Med 2013;368:1279-1290

31.1

21.3

25.9

16.8

0

5

10

15

20

25

30

35

< 0.9 ≥ 0.9HDL Cholesterol (mmol/L)placebo

simvastatin 40mg

% C

HD

Eve

nts

Heart Protection Study

Statins do not alter the risk of Low HDL

Adapted from Heart Protection Study Collaborative Group. Lancet 2003; 361: 2005-2016.

(Diabetes subgroup)

If you needed to treat these lipids what would you prescribe?If you needed to treat these lipids what would you prescribe?

• Total cholesterol Total cholesterol 5.35 mmol/L5.35 mmol/L

• HDL cholesterol HDL cholesterol 1.4 mmol/L1.4 mmol/L

• Triglycerides Triglycerides 1.68 mmol/L1.68 mmol/L

L I P I DL I P I D

LIPID RESULTSLIPID RESULTS

22% reduced mortality22% reduced mortality P<0.001P<0.00124% reduced CHD mortality24% reduced CHD mortality

p<0.001p<0.00129% reduced all CVS outcomes29% reduced all CVS outcomesp<0.001p<0.00120% reduced revascularisation20% reduced revascularisation p<0.001p<0.001

LIPID – Diabetics & Non-LIPID – Diabetics & Non-smokerssmokers

No (%) CHD EventsNo (%) CHD Events

PlaceboPlaceboPravastatinPravastatin

DiabeticsDiabetics 88(23) 88(23) 76(19) 76(19)

Non-smokersNon-smokers 167(13) 167(13) 139(12) 139(12)

New Eng J Med 1998; 339: 1349-57

ASCOTASCOT

• Age 40-79Age 40-79• Untreated BP 160/100 or moreUntreated BP 160/100 or more• Treated BP 140/90 or moreTreated BP 140/90 or more• Total cholesterol < 6.5 mmol/LTotal cholesterol < 6.5 mmol/L• 3+ of LVH,ischaemic ECG,type 2 3+ of LVH,ischaemic ECG,type 2

diabetes,PVD,previous stroke or diabetes,PVD,previous stroke or TIA,male, age > TIA,male, age > 55,smoker,microalbuminuria,family 55,smoker,microalbuminuria,family history of premature CHDhistory of premature CHD

Lancet 2003;361:1149-1158

Figure 2

Source: The Lancet 2003; 361:1149-1158 (DOI:10.1016/S0140-6736(03)12948-0)

Terms and Conditions

Figure 5



CARDS Recruitment CriteriaCARDS Recruitment Criteria

• 2838 T2DM2838 T2DM

• Age 40-75Age 40-75

• No known CVS diseaseNo known CVS disease

• Hypertension or retinopathy or Hypertension or retinopathy or microalbuminuriamicroalbuminuria

• Serum LDL < 4.14 mmol/LSerum LDL < 4.14 mmol/L

• Serum triglycerides < 6.8 mmol/LSerum triglycerides < 6.8 mmol/L

Figure 4



CARDS Baseline CARDS Baseline CharacteristicsCharacteristics

• Total cholesterol Total cholesterol 5.35 mmol/L5.35 mmol/L

• HDL cholesterol HDL cholesterol 1.4 mmol/L1.4 mmol/L

• Triglycerides Triglycerides 1.68 mmol/L1.68 mmol/L

Figure 2



VA-HIT: Diabetic Subgroup Analysis

Arch Intern Med;162:2597-2604

Numbers needed to treatNumbers needed to treatto prevent one non-fatal MI or CHD death in to prevent one non-fatal MI or CHD death in 5 years5 years

All PatientsAll Patients DiabeticsDiabetics

CARECARE 33 33 29 29LIPIDLIPID 28 28 29 29HPSHPS 32 32 31 31VA-HITVA-HIT 23 23 12 12

QuestionQuestion

You are a bigdeal trialist designing a study You are a bigdeal trialist designing a study toto

test the efficacy of a fibrate in the test the efficacy of a fibrate in the prevention of CHD in type 2 diabetes. What prevention of CHD in type 2 diabetes. What ideally would you like the average baseline ideally would you like the average baseline lipid profile to be?lipid profile to be?

FIELD StudyFIELD Study

• 9795 participants9795 participants

• Type 2 diabetesType 2 diabetes

• Age 50- 75 yrsAge 50- 75 yrs

• No prior statin/fibrate therapyNo prior statin/fibrate therapy

• 2131 previous CVS disease2131 previous CVS disease

• 7664 no known previous CVS disease7664 no known previous CVS disease

FIELD - Recruitment LipidsFIELD - Recruitment Lipids

• Total cholesterol 3-6.5 mmol/L +Total cholesterol 3-6.5 mmol/L +

• Either TC:HDL cholesterol > 4Either TC:HDL cholesterol > 4

• Or triglycerides 1.0-5.0 mmol/LOr triglycerides 1.0-5.0 mmol/L

Original Article Effects of Combination Lipid Therapy in Type 2

Diabetes Mellitus

The ACCORD Study Group

N Engl J MedVolume 362(17):1563-1574

April 29, 2010

Lipid Values

The ACCORD Study Group. N Engl J Med 2010;362:1563-1574

Kaplan-Meier Analyses of the Primary Outcome, Expanded Macrovascular Outcome, and Death


Conclusion

• The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone

• These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes

Baseline Characteristics of the Patients


ConclusionsConclusions Statins are safe, benefit many diabetics Statins are safe, benefit many diabetics

and almost all diabetics should be on and almost all diabetics should be on themthem

Treat total cholesterol & LDL cholesterol to Treat total cholesterol & LDL cholesterol to targettarget

There is still a place for fibrates in There is still a place for fibrates in combination and first line for those with combination and first line for those with HDL<1 and/or Tg>2.3HDL<1 and/or Tg>2.3

Documents

Cholesterol and Lipids