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Cholesterol Treatment: New Developments

Cholesterol Treatment: New Developments. Nemanja Stojanović Consultant Endocrinologist Queen’s Hospital, Romford. We will discuss. New Lipid Trials Emerging Trends in CVD research/ problems Several Cases Lipids in Type 2 Diabetes Mellitus

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Cholesterol Treatment: New Developments

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  1. Cholesterol Treatment:New Developments • Nemanja Stojanović • Consultant Endocrinologist • Queen’s Hospital, Romford

  2. We will discuss • New Lipid Trials • Emerging Trends in CVD research/ problems • Several Cases • Lipids in Type 2 Diabetes Mellitus • NICE/ ADA Guidelines for Lipid management in Type 2 Diabetes

  3. Effect of reduction of LDL by 1mmol/l by any means on coronary death and non-fatal MI: meta-analysis of 58 trials Law MR BMJ 2003, 326: 1423-9

  4. Friedwald Formula • LDL= • Rule of Thumb • LDL = (Total cholesterol – HDL) x 0.7 Total Cholesterol - HDL- triglycerides 2.2

  5. Recent Trials

  6. REVERSAL • JUPITER • WOSCOPS • AURORA • Quo vadis CVD Trials

  7. REVERSAL Trial • Intravascular USS study • Primary End Point: % change in atheroma volume • 18 months duration • 502 Patients age 30- 70 • Baseline LDL 3.89 mmol/l • At least 20% coronary a. occlusion on angiogram • Pravastatin 40 mg OD vs Atorvastatin 80 mg OD

  8. REVERSAL

  9. JUPITER Study • Rosuvastatin 20 mg OD vs Placebo • Patients LDL of 3.4 mmol/l • Hs CRP > 2.0 mg/l • 17,802 apparently healthy subjects • 6801 women • No major CVD risk factors

  10. JUPITER Study • Primary End Point: MI, CVA, CVD Death, Unstable angina or Revascularisation • Median follow up 1.9 years • NNT: 95 over 2 years; 31 over 4 years • LDL 50%; Hs CRP 37% • Women benefited as well as men

  11. WOSCOP 2 • The West of Scotland Coronary Prevention Study demonstrated a significant reduction in coronary events after 5 years of treatment with pravastatin as compared with placebo • Participants were followed for an additional 10 years; approximately one third used statins • The rate of coronary events was reduced by 27% over the entire follow-up interval

  12. WOSCOP 2 • Absolute risk reduction is 5.3% for death or hospitalization • NNT 19 for 5 years to prevent an event within 15 years • Ca Prostate…??

  13. AURORA: Rosuvastatin in Haemodialysis Patients • 2776 patients, 50 to 80 years of age on HD • Rosuvastatin 10 mg OD ( n=1391) or placebo (n= 1385) • Primary Outcome: CVD Death, Nonfatal MI or CVA • RESULT: LDL was 43% lower in Hemodialysis 10 Group, but no difference in primary end point

  14. Statin Related Memory Loss • 60 cases described • 36 Simvastatin, 23 Atorvastatin, 1 Pravastatin • 14/ 25 (56%) patients improved after the statin was stopped

  15. NICE Statins Muscle Side Effects • Rhabdomyolisis • 6 fatal cases out of 47 637 active treatment • 3 fatal cases out of 47 170 controls • Miositis • Statins 22/ 43 125 • Control 25/ 42 768

  16. Simvastatin Induced Myopathy • Statin induced Rhabdomyolisis 0.000044/ person/ year • SEARCH Study- Association with: - Higher dose of Simvastatin - Amiodarone - Single Nucleotide Polymorphism (SNP) of SLCO1B1 gene on Chr 12 responsible for majority of cases of myopathy

  17. Type 2 Diabetes Mellitus and Cholesterol Treatment

  18. Treating Lipids…

  19. T2DM and CVD: baseline predictors • LDL cholesterol • Low HDL cholesterol • HbA1C • Systolic blood pressure • Cigarette smoking • Turner RC et al UKPDS (23).BMJ 316:823–828, 1998

  20. Statins vs Fibrates in Type 2 Diabetes

  21. VA-HIT: Conclusions • NNT: 23 patients/ 5 years for 1 event • CVD death or nonfatal MI: 23% reduction • All cause mortality (including cancer and violent deaths): 11%- non significant

  22. HDL • Independent risk factor for IHD • Levels: -Men <1.2 mmol/l -Women <1.4 mmol/l • For every 0.026 mmol/l rise in HDL predicted incidence in coronary events falls 2% in men and 3% in women

  23. Are all these findings applicable in patients with Type 2 DM?

  24. FIELD study • Fenofibrate in 9795 patients with T2DM • 2131 pervious CVS event • Cholesterol 3.0-6.5 mmol/l and Cholesterol/HDL ratio > 4 or trigs 1-5mmol/l

  25. FIELD Endpoints • Primary endpoint: Coronary events (fatal or non-fatal MI) • Secondary endpoints: CVD ( CVAs major CVD events, carotid endarterectomy etc) • Tertiary endpoints: Progression of retinopathy, renal disease etc

  26. FIELD outcomes • CVD morality 5.9 vs 5.2% (p=0.16) • Non fatal MI 24% reduction in FF group (p=0.01) • Total CVD events reduced from 13.9 to 12.5% p=0.04 • Microvascuar disease significant improvement

  27. CARDS • 2838 patients with Type 2 DM • 40-75 year • Placebo 1410 • Atorvastatin 1428 • Women 32% • Caucasian 94% • 15% on aspirin

  28. At least One Complication • Hypertension • Retinopathy/ Maculopathy/ Previous laser • Smoking • Micro or macroalbuminuria • LDL < 4.14 mmol/l • Triglycerides< 6.78mmol/l

  29. CARDS 1% 6% 30% 63%

  30. Starting point

  31. Primary Endpoints • Acute coronary heart disease event (incl. MI, silent MI, unstable angina, death, CPR) • Coronary revascularisation procedures • Stroke

  32. Primary Endpoints: Results • No difference between the sexes or risk factor subgroups • Acute coronary heart disease event 36% • Coronary revascularisation procedures 31% • Stroke 48%

  33. LDL < 2.6mmol subgroup • 743 patients • 26% reduction in major cardiovascular events

  34. Conclusions • NNT 27/event • In 1000 diabetic patients receiving 10mg atorvastatin 50 CVS events will be prevented over 4 year period • The debate now is if there are any patients with Type 2 DM at sufficiently low CVS risk for this treatment to be withheld.

  35. ACCORD Trial • 20 mg Simvastatin + Fenofibrate or Placebo • Due to report in 2009 • Will also look at BP of 120mm Hg vs 140 mmHg Systolic • Average treatment 6 years • ? Hold your breath

  36. Guidelines (NICE/ ADA) and Medications

  37. T2DM Patients Not at High CVS Risk • Normal weight • BP< 140/80mmHg off treatment • Normal ACR/ AER • Non smokers • Do not have high risk lipid profile • No PMH of CVH • No FH of CVD

  38. ADA • In Patients without overt CVD LDL Target is < 2.6 mmol/l • In Patients with overt CVD LDL Target is <1.8 mmol/l

  39. Equivalent Doses + max dose decreases the LDL by additional 20%

  40. We have discussed • Importance of lowering LDL • Recent Developments • Clinical Cases • T2DM Lipid Management • Guidelines and Medications

  41. Summary • CVD can be halted, ? reversed • Primary prevention: still an expanding field • CVD Trials... • Type 2 Diabetes... LDL should be < 2 mmo/l

  42. www.EndoDiabetes.com

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