Prof Jim Mann & Medicine University of Otago Dunedin

There’s More to Lipid Management than Statins – Main Session (Workshop options scheduled) There’s more to lipid management than statins

Jim Mann

Lipid issues 2013

1. Importance of making a lipid diagnosis

2. Update on Familial Hypercholesterolaemia

3. Cholesterol targets

4. Side effects of statins: doses and classes

5. Role of statins in primary prevention

6. Predominant hypertriglyceridaemia

7. Treatment of hypertryglyceridaemic states

8. Case studies

Age 72, CABG, 12 years ago

Initial On Lipitor 20mg Cholesterol 5.6 4.7

Triglyceride 3.0 4.8

HDL Cholesterol 1.0 0.6

LDL Cholesterol 3.4 1.6

Essentials of Human Nutrition 4e (eds Mann & Truswell

Observed & expected deaths from CHD by age group.

Attained age 1980 - 1991 1992 - 2006 (years) SMR 95% CI SMR 95% CI Primary prevention

20 - 39 3750 773 – 10 959 1153 238 - 3372 40 - 59 342 148 – 674 141 75 - 242 60 - 79 27 1 - 153 84 57 - 121 20 - 79 198 102 – 346 103 75 - 138

Neil et al, Eur Heart J, 2008 29; 2625 - 2633 Diagnostic criteria for FH using the Simon Broome Register

Currently available statins

* Simvastatin 10mg  80mg (40mg)

Pravastatin 10mg  40mg/80mg

*Atorvastatin 10mg  80mg (40mg)

Rosuvastatin 5mg  40mg

*MOST LIPOPHILIC Statin hints

• Use a more potent statin rather than high doses of a less potent one

• Worth trying another ‘class’ to help reduce side effects

• Targets are just that. May not always be possible to achieve

• Alternate day treatment may help to reduce side effects Total & LDL Cholesterol Targets (2nd ° prevention)

‘Pre history’ (1970s & T chol < 7.5mmol/l 80s)

2000 – 2004: T chol <5mmol/l or by 20 – 25%

LDL chol < 3mmol/l or by 30%

2008 (NICE): T chol < 4mmol/l LDL chol < 2mmol/l

2013: Lower still depending upon level of risk? NZ Guidelines Group, NZ Primary Care Handbook 2012

NZ Guidelines Group, NZ Primary Care Handbook, 2012 3rd ed. Wellington Odds ratio (95% CI) for all-cause mortality, major coronary events, cerebrovascular events & incidence of cancer (Brugts et al, BMJ, 2009)

Effects of statins on all-cause mortality in randomised trials of participants without prior coronary heart disease at baseline

Ray et al, Arch Intern Med, 2010 Ray et al, Arch Intern Med, 2010

Statins for the Primary Prevention of

Relative risk 95% CI

All cause mortality 0.83 0.73, 0.95

Fatal & non fatal CVD 0.70 0.61, 0.79

Revascularisation rates 0.66 0.53, 0.83

Taylor et al, Cochrane Collaboration (2011) Authors’ Conclusions:

Taylor et al, Cochrane Collaboration (2011)

‘Although reductions in all-case mortality, composite endpoints & revascularisations were found with no excess of adverse events, there was evidence of selective reporting of outcomes, failure to report adverse events & inclusion of people with cardiovascular disease.

Only limited evidence showed that primary prevention with statins may be cost effective and improve patient quality of life. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.’

Widespread use of statins in people at low risk of cardiovascular events, an annual CVD event rate of below 2% observed in the control groups in the trials considered, is not supported by existing evidence.’

Taylor et al, Cochrane Collaboration (2011) Predominant hypertriglyceridaemia (3 – 100mmol/l)

• Secondary to: alcohol excess uncontrolled diabetes (drugs, renal failure, hypothyroidism)

• “Metabolic syndrome”

• Primary hypertriglyceridaemia

• ‘Combined hyperlipidaemia’

Treatment options for hypertriglyceridaemia

• Look for causes

• Diet: reduce adiposity

eliminate (!) alcohol

fat if chylomicrons predominate

if VLDL predominate

• Drugs: Fibrates: gemfibrozil, bezafibrate, fenofibrate n-3 fatty acids (ω3s)

statins

nicotinic acid, tredapative,

nicotinic acid or fibrate & statins& statin Fig 1. Reduction of CHD events by Gemfibrozil in Helinksi Heart Study

Barter et al, Arterioscler Thromb Vasc Biol, 2008 Fig 2. Reduction of CHD events by Fibrates

Barter et al, Arterioscler Thromb Vasc Biol, 2008

Fig 3. Effects of fibrates with the potential to protect against cardiovascular disease

Barter et al, Arterioscler Thromb Vasc Biol, 2008

Table 3. Summary of the effects of nicotinic acid on plasma lipoprotein classes

Carlson, Journal of Internal Medicine, 2005 Case Studies

Case Study (1)

65 year old Pakeha woman: non smoker (lifelong), BP 130/80, weight 65kg (BMI 25), negative family hx

CVRA done using Predict = 4%

How do we manage high LDL?

Fasting 6 = IGT

Cholesterol 7.3 Triglyceride 1.2 HDL Cholesterol 1.84 LDL Cholesterol 5.2 Chol/HDL Ratio 4.7

Patient anxious about her ‘high cholesterol’- does not qualify for a ‘statin’, feels she is not treated aggressively enough?

Case Study (2)

49 year old Maori man. Non smoker, BMI 27.8, BP 140/95 (on meds),CV risk 4% calculated

Issues: asthma, sleep apnoea, viagra use, hypertension Meds: inhibace plus, felodipine (5mg ER), beclazone, salbutamol, alanase

Cholesterol 6.4

Triglyceride 1.4

HDL Cholesterol 1.6 LDL Cholesterol 4.2 Chol/HDL Ratio 4.0

Wanted 6 months of diet & exercise to address this & BP & weight before more meds

Case Study (3)

91 year old lady: abnormal lipid profile, on no lipid therapy.

Fasting status Fasting

Cholesterol 7.3 mmol/l (<4.0) HH

Triglyceride 1.8 mmol/l (< 1.7)HH

HDL Cholesterol 0.87 mmol/l (<2.5) L

LDL Cholesterol 5.6 mmol/l (< 2.5) HH

Chol/HDL Ratio 8.4 (<4.5) H

Past history: 1998: Hypertension, right hemiparesis, complete resolution of CVA, no focal lesion on CT scan

Case Study (4)

80 year old man: has been taking Bezalip since he was 67 years old.

Long standing Hypertension. Meds: Celiprolol, Candesartan Bendrofluazide & Amlodipine

Pre-treatment Most recent:

Fasting status Fasting Fasting

Cholesterol 7.5 (0.0- 5.4) HH 4.8 mmol/l (<4.0) HH

Triglyceride 1.4 (0.0 – 2.1) 0.9 mmol/l (< 1.7)

HDL Cholesterol 1.38 (1.00 – 2.20) 2.02 mmol/l (< 1.00)

LDL Cholesterol 5.5 (0.0 – 3.4) HH 2.4 mmol/l (< 2.5) Risk Factor 5.4 (0.0 – 5.4)

Chol/HDL Ratio 2.4 (<4.5)

Case Study (5)

52 year old Fijian man: Bus & truck driver. Vegan, known , weight 68kg. Height 1.5m, BMI 30.2

HbA1C 7.9% or 63 mmol/l (IFCC) Jan 2011/

Dec 2010 Jan 2011

Total cholesterol 2.9 2.9

Triglyceride 1.3 2.5 HDL Cholesterol 0.29 0.39 LDL Cholesterol 2.0 1.4 Chol/HDL Ratio 10.0 7.6

Suffered ACS/NSTEMI. Underwent 2 vessel PCI: dRCA, pLCx

Case Study (6)

59 year old European man: Truck driver. Chronic atrial fibrillation & previous alcohol excess.

Hypertensive, weight 90kg. Height 1.68m, BMI 31.9

Dec 2007 Jan 2010

Total cholesterol 6.4 6.5

Triglyceride 3.8 2.5 HDL Cholesterol 0.78 0.92 LDL Cholesterol 3.9 4.4 Chol/HDL Ratio 8.2 7.1

Asymptomatic but father died of MI, aged 50 (father was a smoker)