Hyperlipidemia

• Cholestyramine (Questran)
• Colestipol (Colestid)
• Colesevelam (Welchol)

Decrease LDL (mainly)

Increase HDL and (minimally) TG

Adjunct to statin therapy when further LDL lowering is needed

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

• chronic constipation
• increased TGs
• complete biliary obstruction

Immediate Release: Niacor, Nicolar

Intermediate Release: Niaspan

Sustained Relaese: Slo-Niacin, Nicobid

• Decrease TG and LDL (minimally)
• Increase HDL

• 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

• Liver disease
• Active peptic ulcer disease
• Gouty arthritis
• Diabetes (not an absolute CI)

• 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

• Fenofibrate (Tricor) (Micornized Fenofibrate - Lofibra)
• Fenofibric Acid (Trilipix)
• Gemfibrozil (Lopid)

• Decrease TG
• Increase HDL
• Minimal effect on LDL

Fenofibric acid, because it gives the best chance of NOT having myopathy in combo with a statin

• GI (N/D, epigastric discomfort)
• Myopathy (gemfibrozil > fenofibrate)
• Cholelithiasis
• Hepatotoxicity (fenofibrate > gemfibrozil)
• Neutropenia

• Other drugs that cause myopathy: statins (fenofibrate < gemfibrozil), niacin, cyclosporine
• Increases warfarin

Gallstones

• LFTs
• CPK
• Renal fxn
• CBC

• LFTs
• FBG
• Uric Acid
• CPK

GI SEs

• 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)

First line for high TG and/or low HDL

• Rosuvastatin (Crestor)
• Atorvastatin (Lipitor)
• Simvastatin (Zocor)
• Pitavastatin (Livalo)
• Lovastatin (Mevacor, XL is Altoprev)
• Pravastatin (Pravachol)
• Fluvastatin (Lescol, Lescol XL)

• Decrease LDL
• Decrease TG (if < 400) But only Rosuvastatin, Atorvastatin, and Simvastatin do - the others do not
• Increase HDL (minimally)

• 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

• 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

• active liver disease
• pregnancy (really any woman of childbearing age)

• LFTs
• CPK if suspect myopathy
• Renal Fxn

• Watch for s/s of myopathy (skeletal m pain or tenderness)
• Watch for s/s of hepatotoxicity (fatigue, sluggishness, weight loss)

• 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

Pravastatin and Atorvastatin

• Pravastatin's abs decreases with food
• Lovastatin IR's abs increases with food, the SR's decreases

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

• 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?

• 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

• < or equal to 40% needed, use any statin
• 40-60% reduction needed, use atorvastatin or rosuvastatin
• > 60% reduction needed, use combo therapy

• 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

• Decreases LDL
• Decreases TG (minimally)
• Increases HDL (minimally)

• GI - diarrhea, abd pain
• Increased transaminases in combo with statins (monitor LFTs)

Fibric acids (increased risk of cholelithiasis)

AST/ALT if also on statins

• may take with or without food
• pretty well tolerated

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)

• Adjunct for lowering LDL in pts on statins
• Familial hypercholesterolemia, sitolsterolemia

• Decrease TG (only approved for TG >400)
• Possibly increase LDL
• Increase HDL

GI: fishy burp (reduced by taking with food), dyspepsia, taste perversion

fish allergy

• 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

• Treatment of TG >500
• Can safely be combined with statins
• Cardiovascular protection (only 1-2 g needed for this effect)

• when monotherapy fails
• familial hyperlipidemia (Increased TC, LDL, and TGL, Decreased HDL)

yes and they usually give better results than just increasing the doses of individual agents

When used in low doses

lovastatin and niaspan

ezetimibe and simvastatin

pravastatin 40 mg and ASA 81 mg

atorvastatin and amlodipine

simvastatin and Niaspan

statins, niacin, BARs, ezetimibe

fibric acid, niacin, Lovaza

fibric acid, niacin

• 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

• 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.

• 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

• 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

• HDL > 40 for males, > 50 for females
• LDL < 100

glycemic control

• 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

• 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%