Treatment of Dyslipidaemias & The New Grampian Guidelines

Professor Iain BroomDirector, Centre for Obesity Research and Epidemiology

The Robert Gordon UniversityProfessor of Metabolic Medicine, University of Aberdeen

Consultant in Clinical Biochemistry and Metabolic Medicine, NHS Grampian

SECONDARY PREVENTION

PRIMARY PREVENTION (CV Risk Assessment)

PRIMARY PREVENTION

• GLOBAL RISK SCORE (Cholesterol is only one of many Risk Factors)

• RISK ASSESSMENT TOOL

• > 20% RISK OF CV EVENT IN 10 YEARS (40 Years of Age)

What do we know about CV risk? INTERHEART

• Large, international, standardised, case-control study of acute myocardial infarction (AMI) in 52 countries

• To determine the strength of association between various risk factors and AMI

• 15,142 cases and 14,820 controls enrolled to the study

• 9 risk factors were studied

Yusuf S, et al. Lancet 2004; 364: 937–952.

Nine risk factors represent 90.4% of the risk of AMI

• Current or former smoking

• History of diabetes

• History of hypertension

• Abdominal obesity

• Combined psychosocial stressors

• Irregular consumption of fruits and vegetables

• No alcohol intake

• Avoidance of regular exercise

• Raised plasma lipids

Yusuf S, et al. Lancet 2004; 364: 937–952.

Substantial residual CV risk in statin-treated patients

Year of follow-up

Pati

en

ts w

ith

majo

r vascu

lar

even

ts (

%)

The MRC/BHF Heart Protection Study

Placebo Risk reduction=24%

Statin

Heart Protection Study Collaborative Group. Lancet 2002; 360: 7–22.

BHF=British Heart FoundationMRC=Medical Research Council

10

20

30

00 1 2 3 4 5 6

19.8% of statin-treatedpatients had a majorCV event by 5 years

p<0.0001

Abdominal Fat DistributionObesity and Risk

BP 150/95Chol 5.8LDL 4.5HDL 0.8TGs 2.3

BP 120/70Chol 4.4LDL 2.7HDL 1.6TGs 1.0

Effect of Triacylglycerol & HDL Cholesterol on Atherogenicity

HDL HDL

TG TG

apo B Lipoprotein apo B Lipoprotein

High/Intensive Doseage with Statins

I. PROVE-IT (2004)

• Acute coronary syndromes

• 80 mg Atorvastatin v 40 mg Pravastatin

• 3.9% Absolute Risk Reduction

• 16% Relative Risk Reduction

High/Intensive Doseage with Statins

II. TNT (2005)

• Stable Coronary Disease

• 80 mg Atorvastatin v 10 mg Atorvastatin

• 2.2% Absolute Risk Reduction

• 22% Relative Risk Reduction

• 6 x in LFT Derangement

High/Intensive Doseage with Statins

III. SPARCL (2006)

• Post CVA or TIA, no known CHD

• 80 mg Atorvastatin v Placebo

• 2.2% Absolute Risk Reduction in Stroke (5 years) BUT Small Increase in Haemorrhagic Stroke

• 3.5% Absolute Risk Reduction in CV Event (5 years)

• No Difference in Mortality

High/Intensive Doseage with Statins

IV. ASTEROID (2006) [Galaxy Studies]

• Assessment of Coronary Atheroma Burden. 0 & 24 Months Post-Therapy

• 40 mg Rosuvastatin

• LDL-CHOL 53.2% Reduction

HDL OHOL 14.7% Increase

• 6.8% Median Reduction Atheroma Volume

Other studies with high dose Rosuvastatin are underway as part of the GALAXY GROUP

CONCLUSIONS

1. CHOLESTEROL (LDL-CHOLESTEROL) IS IMPORTANT

2. CURRENTLY POWERFUL DRUGS TO REDUCE EFFECTS

3. SHOULD BE USED IN PRIMARY & SECONDARY PREVENTION

4. SIDE-EFFECTS ARE IMPORTANT & CAN MARKEDLY EFFECT QUALITY OF LIFE

5. LIPID PROFILE IS IMPORTANT FOR CORRECT DRUG USAGE

6. DO NOT FORGET TRIACYLGLYCEROL STATINS ARE NOT THE DRUG OF CHOICE