Cholesterol and Lipids TIPS Wokefield Park 15/5/2013

Just a few questions!  What is the NDA target for total cholesterol and LDL cholesterol?  What are the QOF targets for cholesterol?  What is the ideal time to take a statin and why?  Name the most serious side effect of statins.  What blood test would you order if you suspected it?  Name another side effect of statins.  All statins increase HDL cholesterol – true or false?  What is the most typical lipid profile for type 2 diabetes?  What is the most typical lipid profile for type 1 diabetes?

R77 Statins & Ezetimibe For a person who is 40 yrs+ Simvastatin (to 40 mg) unless CVS risk from non-hyperglycaemia-related factors is low (see R72) Simvastatin (to 40 mg) unless CVS risk from non-hyperglycaemia-related factors is low (see R72)

R72 Consider a person to be at high CVS risk unless…… Not overweight Not overweight Normotensive Normotensive No microalbuminuria No microalbuminuria Non-smoker Non-smoker No high risk lipid profile No high risk lipid profile No h/o CVS disease No h/o CVS disease No FH of CVS disease No FH of CVS disease

If low CVS risk………… Assess CVS risk using UKPDS risk engine Assess CVS risk using UKPDS risk engine Start simvastatin if CVS risk > 20% over 10 yrs Start simvastatin if CVS risk > 20% over 10 yrs

Once on a statin……….. Repeat lipid profile in 1-3 months then annually Repeat lipid profile in 1-3 months then annually If total cholesterol>4.0 or LDL cholesterol >2.0 mmol/L titrate simvastatin to 80 mg daily If total cholesterol>4.0 or LDL cholesterol >2.0 mmol/L titrate simvastatin to 80 mg daily

Consider intensifying if……. Existing/newly diagnosed CVS disease Existing/newly diagnosed CVS disease Choose different statin/ezetimibe Choose different statin/ezetimibe

If h/o raised triglycerides……. Consider secondary causes Consider secondary causes Full lipid profile Full lipid profile Prescribe fenofibrate if Tg remain > 4.5 mmol/L Prescribe fenofibrate if Tg remain > 4.5 mmol/L If Tg remain > 2.3 mmol/L consider adding fenofibrate to statin If Tg remain > 2.3 mmol/L consider adding 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:

HDL Cholesterol (mmol/L) placebo simvastatin 40mg % CHD Events Heart Protection Study Statins do not alter the risk of Low HDL Adapted from Heart Protection Study Collaborative Group. Lancet 2003; 361: (Diabetes subgroup)

If you needed to treat these lipids what would you prescribe? Total cholesterol 5.35 mmol/L Total cholesterol 5.35 mmol/L HDL cholesterol 1.4 mmol/L HDL cholesterol 1.4 mmol/L Triglycerides 1.68 mmol/L Triglycerides 1.68 mmol/L

L I P I D

LIPID RESULTS  22% reduced mortalityP<0.001  24% reduced CHD mortalityp<0.001  29% reduced all CVS outcomesp<0.001  20% reduced revascularisationp<0.001

LIPID – Diabetics & Non- smokers No (%) CHD Events No (%) CHD Events PlaceboPravastatin PlaceboPravastatin Diabetics 88(23) 76(19) Non-smokers 167(13) 139(12) New Eng J Med 1998; 339:

ASCOT Age Age Untreated BP 160/100 or more Untreated BP 160/100 or more Treated BP 140/90 or more Treated BP 140/90 or more Total cholesterol < 6.5 mmol/L Total cholesterol < 6.5 mmol/L 3+ of LVH,ischaemic ECG,type 2 diabetes,PVD,previous stroke or TIA,male, age > 55,smoker,microalbuminuria,family history of premature CHD 3+ of LVH,ischaemic ECG,type 2 diabetes,PVD,previous stroke or TIA,male, age > 55,smoker,microalbuminuria,family history of premature CHD Lancet 2003;361:

Figure 2 Source: The Lancet 2003; 361: (DOI: /S (03) )The Lancet 2003; 361: Terms and Conditions

Figure 5 Source: The Lancet 2003; 361: (DOI: /S (03) )The Lancet 2003; 361: Terms and Conditions

CARDS Recruitment Criteria 2838 T2DM 2838 T2DM Age Age No known CVS disease No known CVS disease Hypertension or retinopathy or microalbuminuria Hypertension or retinopathy or microalbuminuria Serum LDL < 4.14 mmol/L Serum LDL < 4.14 mmol/L Serum triglycerides < 6.8 mmol/L Serum triglycerides < 6.8 mmol/L

Figure 4 Source: The Lancet 2004; 364: (DOI: /S (04) )The Lancet 2004; 364: Terms and Conditions

CARDS Baseline Characteristics Total cholesterol 5.35 mmol/L Total cholesterol 5.35 mmol/L HDL cholesterol 1.4 mmol/L HDL cholesterol 1.4 mmol/L Triglycerides 1.68 mmol/L Triglycerides 1.68 mmol/L

Figure 2 Source: The Lancet 2004; 364: (DOI: /S (04) )The Lancet 2004; 364: Terms and Conditions

VA-HIT: Diabetic Subgroup Analysis Arch Intern Med;162:

Numbers needed to treat to prevent one non-fatal MI or CHD death in 5 years All PatientsDiabetics  CARE  LIPID  HPS  VA-HIT 23 12

Question You are a bigdeal trialist designing a study to You are a bigdeal trialist designing a study to test the efficacy of a fibrate in the prevention of CHD in type 2 diabetes. What ideally would you like the average baseline lipid profile to be? test the efficacy of a fibrate in the prevention of CHD in type 2 diabetes. What ideally would you like the average baseline lipid profile to be?

FIELD Study 9795 participants 9795 participants Type 2 diabetes Type 2 diabetes Age yrs Age yrs No prior statin/fibrate therapy No prior statin/fibrate therapy 2131 previous CVS disease 2131 previous CVS disease 7664 no known previous CVS disease 7664 no known previous CVS disease

FIELD - Recruitment Lipids Total cholesterol mmol/L + Total cholesterol mmol/L + Either TC:HDL cholesterol > 4 Either TC:HDL cholesterol > 4 Or triglycerides mmol/L Or triglycerides mmol/L

Original Article Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus The ACCORD Study Group N Engl J Med Volume 362(17): April 29, 2010

Lipid Values The ACCORD Study Group. N Engl J Med 2010;362:

Kaplan-Meier Analyses of the Primary Outcome, Expanded Macrovascular Outcome, and Death The ACCORD Study Group. N Engl J Med 2010;362:

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

Conclusions Statins are safe, benefit many diabetics and almost all diabetics should be on them Statins are safe, benefit many diabetics and almost all diabetics should be on them Treat total cholesterol & LDL cholesterol to target Treat total cholesterol & LDL cholesterol to target There is still a place for fibrates in combination and first line for those with HDL 2.3 There is still a place for fibrates in combination and first line for those with HDL 2.3