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Aggressive Therapy for Hypercholesterolemia: Data, Strategy and Outcomes

Aggressive Therapy for Hypercholesterolemia: Data, Strategy and Outcomes. Timothy A. Denton, M.D. High Desert Heart Institute Victorville, CA. Can you identify these?. Chylomicrons. VLDL. E. B100. E. B100. AI. HDL1. AII. AI. AIV. AII. CI. CIII. CII. CII. B48. HDL2. B100.

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Aggressive Therapy for Hypercholesterolemia: Data, Strategy and Outcomes

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  1. Aggressive Therapy for Hypercholesterolemia:Data, Strategy and Outcomes Timothy A. Denton, M.D. High Desert Heart Institute Victorville, CA

  2. Can you identify these?

  3. Chylomicrons VLDL E B100 E B100 AI HDL1 AII AI AIV AII CI CIII CII CII B48 HDL2 B100 IDL CI AI CII CIII AII E Remnants E HDL3 B100 LDL AI B48 AII

  4. Event Standard Approach to LDL Management 6 months Diet Diet Drugs Exercise

  5. A Probabilistic Equation P(success | overall population) = P(success | ideal population) * P(compliance | overall population)

  6. Methods for Modifying Cholesterol Levels 1 - Diet 2 - Exercise 3 - Drugs 4 - Partial ileal bypass 5 - Portacaval shunting 6 - Apheresis adsorption column (LDL apheresis) plasma exchange double membrane dextran sulfate precipitation immunoabsorption 7 - Liver transplantation

  7. Diet

  8. Lifestyle Heart Trial Ornish D, et al. Lancet 1990;336:129

  9. Lifestyle Heart Trial Ornish D, et al. Lancet 1990;336:129

  10. Lifestyle Heart Trial Intervention group LDL after 1 year Mean = 93 mg/dl + 43 mg/dl NCEP Goal 55.3% 44.7% Ornish D, et al. Lancet 1990;336:129

  11. Biosphere

  12. Biosphere2 Dietary Restriction • Biosphere 2 • “Isolated, confined environment”, 2 years • 8 subjects • Green and yellow vegetables • Animal products of 1 egg, 112 g of meat, 500 cc of goat milk per WEEK • All had consistent weight loss for 2 years • Blood samples q 1-2 months Verdery, et al. Arch Intern Med 1998;158:900

  13. Biosphere2 Dietary Restriction Verdery, et al. Arch Intern Med 1998;158:900

  14. Biosphere2 Dietary Restriction LDL after 2 years Mean = 58 + 7 mg/dl NCEP Goal 100% 0% Verdery, et al. Arch Intern Med 1998;158:900

  15. Dietary “Success”

  16. Exercise

  17. Effect of Fitness on Survival Blair JAMA 1989;262:2395

  18. Effect of Fitness on Survival Blair JAMA 1989;262:2395

  19. 500-1000 Cal 1000-2000 Cal 2000-3000 Cal 500 Cal >3000 Cal Sesso et al. Circ 2000;102:975-980 Harvard Alumni Health Study 4.2 kJ = 1 kcal

  20. Effect of Exercise on Lipids • 2906 men • age 30-64 years • exercise treadmill test to exhaustion • classified into 6 groups based on average miles run per week Kokkinos Arch Int Med 1995:155:415

  21. Effect of Exercise on Lipids Kokkinos Arch Int Med 1995:155:415

  22. Running 21-60 Miles per Week Mean = 121 + 29 mg/dl NCEP Goal 22.9% 77.1% Verdery, et al. Arch Intern Med 1998;158:900

  23. Cholesterol-Lowering Drugs

  24. Cholesterol Modifying Agents

  25. Achievement of NCEP Goal atorva = atorvastatin (Lipitor) simva = simvastatin (Zocor) lova = lovastatin (Mevacor) fluva = fluvastatin (Lescol) colest = colestipol (Colestid) Brown, JACC 1998; 32:665

  26. Achievement of NCEP Goal P=NS P=NS P=NS Brown, JACC 1998; 32:665

  27. Statins Prava Simva Atorv Rosuva Jones et al. Am J Cardiol2003;92:152

  28. 4S Survival Curves Lancet 1994;344:1383

  29. (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering) • 122 centers -- Europe, North America, South Africa, Australasia • adults with chest pain x15 min • exclusion coronary revascularization planned cholesterol >270 mg% Q-wave MI 3 months CABG, 6 months PTCA, 4 weeks MI LBBB, CHF III, other drugs, DM, preg MIRACL Schwartz JAMA 2001;285:1711

  30. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Ischemic events P=0.048 MIRACL Schwartz JAMA 2001;285:1711

  31. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering CVA P=0.02 MIRACL Schwartz JAMA 2001;285:1711

  32. Cumulative Incidence of First Ischemic Events • 341 pts • CCS 0,I • PTCA vs MedRx Pitt, B. et al. N Engl J Med 1999;341:70-76

  33. Reversal of Atherosclerosis with Aggressive Lipid Lowering • DB Random atorv v. prava (79 v. 110) • IV US • Atheroma vol REVERSAL P=0.02 Nissen JAMA 2004;291:1071

  34. Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm P=0.0005 • 19,342 HTN + 3 RF • Tchol < 250 • Atorva v placebo • trial stopped 3.3 yrs P=0.16 P=0.0005 P=0.024 P=0.0005 ASCOTT-LLA Nissen JAMA 2004;291:1071

  35. Atorvastatin Comparative Cholesterol Efficacy and Safety Study • 3,387 • 54 weeks • Atorva, fluva, lova, prava, simva • titrate to LDL < 100 ACCESS Smith Phamacoeconomics 2003;21:13

  36. Baycol (cerivastatin) 12/1/2000 -- FDA approves 0.8 mg 3/30/2001 -- FDA warning about metabolism 8/1/01 -- 31 US deaths, 19 lone drug, 12 in combination 8/8/2001 -- Bayer removes Baycol from US Market

  37. When should weSTARTtherapy?

  38. (Cardiac Hospitalization Atherosclerosis Management Program) • UCLA • Observational / Interventional • AHA Guidelines • Standard orders, education, DC planning • Phone follow-up CHAMP Fonarow, AJC 2001;87:819

  39. CHAMP Fonarow, AJC 2001;87:819

  40. CHAMP Fonarow, AJC 2001;87:819

  41. When should weSTARTtherapy? AS SOON AS POSSIBLE!!!!

  42. But my hospitalized patient’s LDL is at goal.

  43. Original paper reports total cholesterol Converted to LDL by assuming LDL = 0.67 * total cholesterol Brugada, Cardiology 1996;87:194

  44. But my hospitalized patient’s LDL is at goal. Not for long…

  45. Event Aggressive Approach to LDL Management X Drug therapy Diet Exercise

  46. The Guidelines

  47. How often do we provide these therapies?

  48. State Standings Ranked by CV indicators, mammog, immune, etc Jencks et al. JAMA 2000;284:1670

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