1. Name 3 Bile Acid Resins
    • Cholestyramine (Questran)
    • Colestipol (Colestid)
    • Colesevelam (Welchol)
  2. What effects do bile acid resins have on lipids?
    Decrease LDL (mainly)

    Increase HDL and (minimally) TG
  3. What place do bile acid resins have in therapy?
    Adjunct to statin therapy when further LDL lowering is needed
  4. Side effects of bile acid resins
    Not absorbed, so no systemic SEs

    GI (nausea, constipation, bloating, flatulence)

    to minimize: take with meals, start low and go slow, more fiber, more H2O, stool softener, sip through straw

    Gritty texture - mix with fluid, soup, pulpy fruits

    Binds other drugs, so take other drugs one hour before or 4 hours after
  5. Bile acid resin Contraindications
    • chronic constipation
    • increased TGs
    • complete biliary obstruction
  6. What Niacin (nicotinic acid) products are available?
    Immediate Release: Niacor, Nicolar

    Intermediate Release: Niaspan

    Sustained Relaese: Slo-Niacin, Nicobid
  7. Effects of Niacin on lipids
    • Decrease TG and LDL (minimally)
    • Increase HDL
  8. Side Effects of Niacin and how to minimize/avoid them
    • Flushing, warmth, or itching of face or neck (Titrate dose up, Take at bedtime after a small snack, Avoid taking hot beverages with it, ASA or Ibuprofen 30 minutes prior)
    • GI - N/V/D, dyspepsia, activation of peptic ulcer (Avoid in pts with peptic ulcer disease)
    • Myopathy (very rare)(watch for s/s: skeletal m. pain, weakness, tenderness)
    • Hepatotoxicity (watch for signs: fatigue, sluggishness, weight loss)
    • Hyperuricemia
    • Hyperglycemia
  9. Niacin CIs
    • Liver disease
    • Active peptic ulcer disease
    • Gouty arthritis
    • Diabetes (not an absolute CI)
  10. Niacin starting doses
    • Immediate Release: 250 mg BID. Gradually incr by 500 mg BID up to tolerated dose (max 6 g)
    • Intermediate Release: 500 mg QHS x 1 month, then 1000 mg QHS (max = 2 g)
    • Sustained Release: 250 mg BID, gradually incr by 250 mg BID up to 1-2 g QD
  11. Name 3 Fibric Acids
    • Fenofibrate (Tricor) (Micornized Fenofibrate - Lofibra)
    • Fenofibric Acid (Trilipix)
    • Gemfibrozil (Lopid)
  12. Fibric Acids effect on lipids
    • Decrease TG
    • Increase HDL
    • Minimal effect on LDL
  13. Which fibric acid is the best to use in combo with a statin and why?
    Fenofibric acid, because it gives the best chance of NOT having myopathy in combo with a statin
  14. SEs of Fibric Acids
    • GI (N/D, epigastric discomfort)
    • Myopathy (gemfibrozil > fenofibrate)
    • Cholelithiasis
    • Hepatotoxicity (fenofibrate > gemfibrozil)
    • Neutropenia
  15. DIs of Fibric Acids
    • Other drugs that cause myopathy: statins (fenofibrate < gemfibrozil), niacin, cyclosporine
    • Increases warfarin
  16. Fibric Acid CIs
  17. Monitoring with Fibric Acids
    • LFTs
    • CPK
    • Renal fxn
    • CBC
  18. Monitoring with Niacin
    • LFTs
    • FBG
    • Uric Acid
    • CPK
  19. Monitoring with Bile Acid Resins
    GI SEs
  20. Patient Education for Fibric Acids
    • Take gemfibrozil 30 min before meals
    • Watch for s/s of myopathy (skeletal m pain or tenderness)
    • Watch for s/s of hepatotoxicity (fatigue, sluggishness, weight loss)
    • Watch for s/s of gallstones (bloating, upper abd discomfort, intolerance to fried foods)
  21. Fibric Acids place in therapy
    First line for high TG and/or low HDL
  22. Name the HMG CoA Reductase Inhibitors (statins) in order of decreasing potency as far as LDL lowering effects go
    • Rosuvastatin (Crestor)
    • Atorvastatin (Lipitor)
    • Simvastatin (Zocor)
    • Pitavastatin (Livalo)
    • Lovastatin (Mevacor, XL is Altoprev)
    • Pravastatin (Pravachol)
    • Fluvastatin (Lescol, Lescol XL)
  23. Statin effects on lipids
    • Decrease LDL
    • Decrease TG (if < 400) But only Rosuvastatin, Atorvastatin, and Simvastatin do - the others do not
    • Increase HDL (minimally)
  24. Statin SEs
    • Myopathy: Myalgias, Miositis, Myopathy, Rhabdomyolysis (may be decr using CoQ10 supplementation or reversed with Vitamin D if Vitamin D level is low)
    • Hepatitis (rare - 1-2%)
    • CNS - insomnia, vivid dreams, difficulty sleeping/concentrating (rare - if occurs, use pravastatin or atorvastatin b/c they're less lipid soluble)
    • Proteinuria/hematuria (assoc with rosuvastatin, but not assoc with worsening renal fxn)
    • Pregnancy category X
  25. Statin DIs
    • Other drugs that cause myopathy (fibric acids, niacin, cyclosporine, erythromycin)
    • CYP 3A4 inhibitors (atorva, lova, simva)
    • CYP 2C9 inhibitors (fluva, rosuva)
    • May increase warfarin d/t competition for 3A4 or 2C9 metabolism
  26. Statin CIs
    • active liver disease
    • pregnancy (really any woman of childbearing age)
  27. Statin monitoring
    • LFTs
    • CPK if suspect myopathy
    • Renal Fxn
  28. Patient Education for Statins
    • Watch for s/s of myopathy (skeletal m pain or tenderness)
    • Watch for s/s of hepatotoxicity (fatigue, sluggishness, weight loss)
  29. Distinguish between myalgia, miositis, myopathy, and rhabdomyolysis. When/how can they be resolved?
    • Myalgias: m pain or weakness - no change in CPK
    • Miositis: m pain or weakness - increase in CPK
    • Myopathy: disease of the muscles - increase in CPK > 10x ULN (may be caused by CoQ10 deficiency)
    • Rhabdomyolysis: m pain or weakness - increase in CPK and SCr, usually with brown urine and urinary myoglobin

    Usually assoc with DIs or high statin doses - stop statin - usually resolves within a month after stopping
  30. Which statins are hydrophilic?
    Pravastatin and Atorvastatin
  31. Which statins are affected by food?
    • Pravastatin's abs decreases with food
    • Lovastatin IR's abs increases with food, the SR's decreases
  32. What was the CURVES study?
    It compared various doses of HMG CoA Reductase Inhibitors.

    • Findings:
    • Very flat dose-response curve
    • Doubling the minimal effective dose only increased the LDL lowering effects by 5-15%
    • Established comparative potency of statins
  33. What other benefits might statins have?
    • CV: decr inflammation and CRP, alter platelet aggregation - suppress thrombin generation, reduce plasma viscosity, stabilize plaque, improve endothelial fxn, possibly decr atrial fib
    • Reduce fracture risk
    • Prevent/delay development of diabetes, dementia, RA, CKD?
  34. Statins place in therapy
    • First line agents to decrease LDL
    • May be helpful to decr TG (200-400 mg/dl) (atorvastatin, rosuvastatin, simvastatin)
    • Prevention of CAD related morbidity and mortality
  35. What is the therapy for < 40% LDL reduction, 40-60% LDL reduction, and > 60% LDL reduction?
    • < or equal to 40% needed, use any statin
    • 40-60% reduction needed, use atorvastatin or rosuvastatin
    • > 60% reduction needed, use combo therapy
  36. When should a statin be stopped?
    • When AST/ALT is > 3x ULN
    • Myalgias (may be able to lower dose instead of d/c)
    • Pregnancy
    • NOT when a pt is having an acute coronary syndrome
    • Age? maybe d/c in elderly with limited life expectancy, high risk of SEs, etc
  37. Effect of Ezetimibe (Zetia) on lipids
    • Decreases LDL
    • Decreases TG (minimally)
    • Increases HDL (minimally)
  38. Ezetimibe SEs
    • GI - diarrhea, abd pain
    • Increased transaminases in combo with statins (monitor LFTs)
  39. DIs with Ezetimibe
    Fibric acids (increased risk of cholelithiasis)
  40. Ezetimibe monitoring
    AST/ALT if also on statins
  41. Patient education for ezetimibe
    • may take with or without food
    • pretty well tolerated
  42. What was the ENHANCE study?
    Randomized placebo controlled trial looking at simvastatin vs. Vytorin (simvastatin + ezetimibe) in regard to intima-media thickness (IMT)

    • Results:
    • no diff in IMT
    • combo signific decr LDL over monotherapy
    • more deaths seen in monotherapy (but trial not powered to assess this)
  43. Ezetimibe place in therapy
    • Adjunct for lowering LDL in pts on statins
    • Familial hypercholesterolemia, sitolsterolemia
  44. Effects of Omega-3 acid ethyl esters (Lovaza) on lipids
    • Decrease TG (only approved for TG >400)
    • Possibly increase LDL
    • Increase HDL
  45. Lovaza SEs
    GI: fishy burp (reduced by taking with food), dyspepsia, taste perversion
  46. Lovaza CIs
    fish allergy
  47. Patient education for Lovaza
    • Don't take with OTC fish oil products
    • OTC products haven't gone through the extensive purification process, so less safe (more toxic pollutants) and less potent
  48. Omega-3 ethyl acid esters place in therapy
    • Treatment of TG >500
    • Can safely be combined with statins
    • Cardiovascular protection (only 1-2 g needed for this effect)
  49. When is combo therapy used?
    • when monotherapy fails
    • familial hyperlipidemia (Increased TC, LDL, and TGL, Decreased HDL)
  50. Are the lipid lowering effects of combinations additive?
    yes and they usually give better results than just increasing the doses of individual agents
  51. When can drug combos reduce toxicity?
    When used in low doses
  52. What is Advicor a combo of?
    lovastatin and niaspan
  53. What is Vytorin a combo of?
    ezetimibe and simvastatin
  54. What is Pravigard a combo of?
    pravastatin 40 mg and ASA 81 mg
  55. What is Caduet a combo of?
    atorvastatin and amlodipine
  56. What is Simcor a combo of?
    simvastatin and Niaspan
  57. Which antihyperlipidemic agents lower LDL?
    statins, niacin, BARs, ezetimibe
  58. Which antihyperlipidemics lower TGs?
    fibric acid, niacin, Lovaza
  59. Which antihyperlipidemics increase HDL?
    fibric acid, niacin
  60. What are the steps for treatment of hyperlipidemia according to the NCEP ATP III guidelines?
    • 1. Determine lipoprotein levels (fasting lipid panel)
    • 2. Identify presence of atherosclerotic disease that confers high risk for CHD (CHD risk equivalent - Clinical CHD, Symptomatic CAD, PAD, Diabetes, Framingham risk >20%, abdominal aortic aneurysm)
    • 3. Determine presence of major risk factors other than LDL (Modifiable - cigarette smoking within past month, HTN > 140/90 or on HTN meds, low HDL <40, men 45 y.o.+, women 55 y.o. + or premature menopause w/o ERT, family hx of premature CAD - AMI or sudden cardiac death - men 55 +, women 65+) (negative risk factor is HDL > 60)
    • 4. If 2+ risk factors other than LDL are present w/o CHD or CHD risk equivalent, asssess 10-year CHD risk (Framingham risk score)
    • 5. Determine risk category; establish LDL goal, determine need for TLC or drug therapy
    • 6. Initiate therapeutic lifestyle changes (TLC) if LDL is above goal
    • 7. Consider adding drug therapy if LDL exceeds level determined in step 5 (address LDL first unless TG > 500)
    • 8. Identify metabolic syndrome and treat, if present, after 3 months of TLC
    • 9. Treat elevated TGs
    • 10. Treat low HDL
  61. In step 5, determining the risk category and establishing goals and necessity of tx, what are the LDL and non-HDL goals for the different risk categories, and when do we start lifestyle changes and/or drug therapy?
    • If the pt has CAD or a CAD risk equivalent: the goal LDL is < 100. If LDL is > 100 initiate lifestyle changes. If LDL is > 130 start drug therapy. Non-HDL goal is < 130.
    • If the pt has 2+ risk factors (using the Framingham risk score): the goal LDL is < 130. If LDL is > 130 initiate lifestyle changes. If LDL is > 130 with a 10 year risk of 10-20% or if LDL is > 160 with a 10 year risk < 10% initiate drug therapy. Non-HDL goal is < 160.
    • If the pt has 0-1 risk factors: goal LDL is < 160. If it is > 160 start lifestyle changes. If it is above 190, start drug therapy. Non-HDL goal is < 190.
  62. What are the criteria for metabolic syndrome?
    • Abdominal Obesity - Men waist circumference > 40 inches, women > 35 inches
    • Triglycerides greater than or equal to 150
    • HDL less than 40 for men and less than 50 for women
    • BP greater than or equal to 130/85
    • Fasting glucose 110 or greater
  63. Drugs of choice for hyperlipidemia according to lipid abnormality
    • high LDL - 1st line is statin, second line is niacin (then BAR or ezetimibe)
    • high LDL and TG - 1st line is niacin (if TG > 400), 2nd line is statin (if TG < 400)
    • high LDL and TG and low HDL - 1st line is niacin if pt not diabetic, 2nd line is statin if pt is diabetic
    • high TG - 1st line is fibric acid, 2nd line is niacin, Lovaza, or statin
    • high TG and low HDL - 1st line is fibric acid, 2nd line is niacin
    • low HDL - 1st line is fibric acid, 2nd line is niacin
  64. Lipid goals for diabetics. Aside from diet exercise, and weight loss, control of what is important in these patients?
    • HDL > 40 for males, > 50 for females
    • LDL < 100

    glycemic control
  65. How do we monitor for efficacy with antihyperlipidemics?
    • Get a lipid panel at baseline, then 8 weeks, then q 2-3 months until stable, then q 6-12 months
    • Monitor compliance with meds and TLC
  66. What are the Heart Protection Study, PROSPER, ALLHA-LLT, ASCOT-LLA, PROVE IT-TIMI22?
    • Trials published since ATP III was published.
    • Studied over 50,000 pts, including high CAD risk pts
    • Results: some pts may benefit from intensive statin tx and it should be extended to older pts, goal should be LDL of 70 or less or a 30-40% reduction
    • For every 1% decrease in LDL, relative risk for CHD events decreases by 1%
Card Set
Therapeutics Week 11 - Hyperlipidemia