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A. Overview [1,2] navigator

  1. Low fat or Mediterranean diet should be implemented in all patients
  2. Combination of diet and pharmacologic therapy usually required to achieve goals
  3. Assess risk factors prior to selection of initial therapy [6]
  4. HMG CoA Reductase Inhibitors (statins) are first line
  5. Cholesterol Absorption Inhibitor
  6. Niacin
  7. Bile Acid Sequestrants
  8. Fibric Acid Derivatives
  9. Lipid Level Therapy Goals [2]
    1. Overall, goal total cholesterol (chol) <200mg/dL
    2. Chol to HDL ratio goal <5.0 in average risk patients is important
    3. Reduction of LDL to <110mg/dL usually advocated
    4. Reductions of chol in high risk patients to LDL <100mg/dL are often recommended but data supporting these recommendations are sparse [8]
    5. Most experts recommend increasing HDL to >40mg/dL, particularly in diabetics [13]
  10. Many of these agents affect atherogenesis as well as chol
  11. Drug combinations should be used when goals cannot be achieved with single agents [1]

B. HMG CoA Reductase Inhibitors (Statins) [1,5]navigator

  1. Indications
    1. Types IIa and IIb primary hypercholesterolemia and high LDL chol
    2. First line agents for total chol (T-Chol) reduction
    3. Primary and secondary prevention of CAD in persons with high T-Chol
    4. Primary and secondary prevention of CAD in persons with normal T-Chol and low HDL [21]
    5. Approximately 10 patients treated for every one acute cardiac event prevented
    6. Any patient at high risk of heart disease or stroke, even with normal T-Chol [24]
    7. 25-40% reduction in LDL chol and 25-35% reduction in T-Chol
    8. ~20% reduction in progression to myocardial infarction (MI) in patients with acute coronary syndromes (ACS) [90,91]
    9. Reduction of LDL <120mg/dL leads to significant atherosclerotic plaque reduction
    10. In Type 2 Diabetes (DM2), fasting lipid goals: LDL <100mg/dL, HDL >45mg/dL, triglycerides <200mg/dL with moderate to high dose statins [86,87]
    11. Reduces primary and secondary risk of stroke 15-25% [48]
    12. Reduce restenosis rates after coronary angioplasty [67] and stent placement [68]
    13. Goal T-Chol levels for secondary prevention are probably around 100mg/dL [45]
    14. Early versus no statin use after ACS showed no difference in 90 day and 1 year mortality or MI in some [73,100] but not all [88,90] studies
    15. Reducing LDL to <100mg/dL in all patients with ACS showed clear benefits [91]
    16. Reducing LDL to <80mg/dL in patients with stable CAD with atorvastatin 80mg reduced major cardiovascular (CV) events but not overall mortality [19]
    17. High dose statins have consistently shown reductions in CV events over standard doses [111]
  2. Overall Effects of Statin Therapy [5]
    1. Aggressive statin therapy reduces chol and CRP and causes plaque regression [10,11,28]
    2. Statin therapies reduce major cardiac events by 20-30% [31]
    3. Reduce MI, stroke, revascularization rates all by 25-33% regardless of chol levels [18]
    4. Statin use associated with ~50% reduction in initial MI [4]
    5. Statins are associated with 50-70% reduction in dementia risk [51]
    6. Reduce overall mortality 21% (12% per mmol/L reduction in LDL chol) in CAD patients
    7. Statins associated with ~25% reduction in death or hospitalization in patients with congestive heart failure (CHF) not previously on statins [103,108]
    8. Statin use immediately post-MI (regardless of lipid levels) led to a 25% reduction in mortality [53]
    9. Reduce vascular events and mortality (by 9%) in diabetic patients [3]
    10. Aggressive, high stain doses generally well tolerated and reduced CV events over standard doses, but myositis risk increased [93,111]
    11. Generally, simvastatin generic recommended as first line 10mg-20mg po qd [111]
    12. If drug interactions are a concern, then pravastatin 20mg qd first line recommended [111]
  3. Effects on HDL chol and triglycerides
    1. Most agents cause 5-7% increase in HDL chol
    2. Most agents show 5-15% reduction in triglycerides
    3. Most agents can reduce apolipoprotein B ~20%
    4. Atorvastatin can provide ~25% triglyceride reduction and >10% HDL increase [7]
  4. Reduction of Vascular Inflammation [10,11]
    1. Anti-inflammatory effects with ~15% reduction of C-Reactive Protein (CRP) [14,65]
    2. Reduction in CRP levels is independently associated with good CV outcomes
    3. Patients with CV disease should have CRP levels monitored for prognostic information
  5. Additional Biochemical Activities
    1. These agents do much more than simply reduce chol levels
    2. Improves endothelial function including vasodilation (nitric oxide production)
    3. Certain statins block LFA-1 interaction with ICAM-1 on inflammatory cells [65]
    4. Depletion and physicochemical stability of lipid core
    5. Strengthening of fibrous cap on atheromata
    6. Inhibition of platelet thrombus formation and deposition
    7. Reduction of thrombogenic response
    8. Increased nitric oxide levels
    9. Inhibits transcription factor NF-kB in renal cells; may reduce fibrosis [46]
    10. Inconclusive effects on platelet aggregation [14]
    11. Do not reduce fracture risk or increase bone density [42]
  6. Atorvastatin (Lipitor®) [7]
    1. Reduces total and LDL chol up to 50-60%
    2. Reduces VLDL chol and triglycerides by 20-30%
    3. Increases HDL-chol by ~5%
    4. Dose is 20-80mg po qpm
    5. Drug is FDA approved for both primary hypercholesterolemia and mixed lipid disorders
    6. May be particularly useful in diabetics with very high triglycerides
    7. Prevents atherosclerosis progression in familial hypercholesterolemia (80mg qd) [56]
    8. Atorvastatin 80mg po qd reduced recurrent ischemic events 16% within the 16 weeks after the ACS episode [59] and 16% better than pravastatin 40mg qd [88]
    9. Atorvastatin treatment in patients with HTN and average or low chol levels reduces and CV events ~30% [81]
    10. In age >65 with CAD and LDL <130mg/dL, 80mg superior to 10mg atorvastatin for reducing all CV events [87]
    11. Treatment of patients with cardiac ischemia unsuitable for revascularization with up to 80mg qd atorvastatin reduces symptoms and improves cardiac function [41]
    12. Atorvastatin 80mg qd reduces lipid and CRP levels and atherosclerotic progression far better than high dose pravastatin 40mg qd [83]
    13. Atorvastatin 80mg po qd reduced recurrent stroke after TIA or stroke but no known CAD by 16%, and reduced major cardiovascular events 20% within 5 years [31]
    14. In patients with previous MI, atorvastatin 80mg qd reduced major coronary events and non-fatal MI more than simvastatin (Zocor®) 20mg qd [98]
    15. Atorvastatin 40mg po qd added to disease modifying drugs reduced joint inflammation and inflammatory markers in rheumatoid arthritis [93]
    16. Caduet® is amlopidine (Plendil®) in combination with atorvastatin
  7. Pravastatin (Pravachol®)
    1. Indicated for reduction in chol and primary prevention in CAD
    2. Also indicated for reduction of stroke in patients with vascular disease
    3. Dose 20-40 mg po qhs (80mg may be given)
    4. Reduces LDL chol 34-38%, triglycerides 24%, and increases HDL 12%
    5. Regression of atherosclerotic plaque progression has been demonstrated
    6. Interacts with cholesteryl-ester transport pathway (CETP)
    7. Treatment with pravastatin post-MI in elderly with normal cholesterol reduced the incidence of recurrent MI, stroke, hospitalization, and death by 30-45%
    8. Reduced severe coronary events in diabetics with normal cholesterol levels who had an initial MI by 25% over 5 years [29]
    9. Pravastatin reduced risk of stroke from 4.5% to 3.7% in patients with CAD [48]
    10. Reduced reinfarction and hospitalization >20% in patients with acute coronary syndromes regardless of cholesterol [52]
    11. Pravastatin reduces major cardiac events and death >20% in CAD patients (even with normal lipids), particularly women and patients >65 years old [61,72]
    12. Treatment of mild CRF patients with pravastatin reduced CV events >25% [78]
    13. Pravastatin 20-40mg qd for 2 years in children with homozygous familial hypercholesterolemia was safe and reduced carotid atherosclerosis [94]
    14. Pravastatin 10-20mg qd added to diet reduced CV events 33% in Japanese persons with high cholesterol in primary prevention study [20]
    15. Pravastatin for 5 years reduces coronary events for 10 years in men without MI [105]
  8. Simvastatin (Zocor®)
    1. Indicated for reduction in chol and secondary prevention in CAD
    2. Dose10-80mg po qpm
    3. Reduction in LDL 40-47%
    4. Reduction in triglycerides 18%
    5. Increase in serum HDL 12%
    6. Reduces risk of MI, stroke, or revascularization 25-33% regardless of chol levels [18]
    7. Reduces risk of first non-hemorrhagic stroke 25% within 2 years
    8. High dose (40mg/d) simvastatin for 6 months improved walking distance, ankle-brachial pressure indices, and claudication in patients with peripheral vascular disease [66]
    9. Low dose simvastatin + colesevelam are additive and safe [60]
    10. Vytorin®, combined simvastatin + ezetimibe, more effectively reduces Chol than either alone, and similar safety to simvastatin alone [95,97]
    11. Mediterranean diet with simvastatin more effective than either alone [69]
    12. Combination simvastatin + niacin more effective than simvastatin alone for secondary prevention of CV events in patients with normal LDL and low HDL [21]
    13. Slow release niacin (Niaspan®) with simvastatin (Simcor®) now FDA approved, similar to Advicor® (above) [110]
  9. Rosuvastatin (Crestor®) [35]
    1. Very potent statin with excellent chol reductions at relatively reduced price
    2. Reduction of LDL Chol to ~60mg/dL with high dose rosuvastatin leads to significant reduction in coronary atherosclerosis at 2 years [25]
    3. LDL Chol reduction to ~80mg/dL 40mg qd rosuvastatin in low CV risk patients caused regression of carotid intima-media thickness over 1-2 years versus increase in placebo [16]
    4. In persons age >59 years with systolic CHF, 10mg qd rosuvastatin reduced hospitalizations for CV causes ~20% and did not cause safety problems [108]
    5. Adverse effects similar to other statins
    6. Overall 0.5% of patients had transaminase elevations >3X normal
    7. Overall 0.3% of patients had creatine kinase levels >10X normal
    8. Myopathy and muscle symptoms in 0.1% of patients
    9. Dose initially 10mg qd up to maximum dose 40mg qd; 5mg tablets available
  10. Lovastatin (Mevocor®)
    1. Indicated for reduction of chol and for primary prevention
    2. Dose 20-40mg po qhs or bid (maximum dose 80mg in 24 hours)
    3. In patients with average T-Chol and <40mg/dL HDL, reduced risk of CV events ~35%
    4. Well tolerated overall; caution with other hepatotoxic drugs (including niacin)
    5. Also effective and safe in heterozygous familial hypercholesterolemia [33]
    6. Generic lovastatin (Altocor®) less expensive, as effective as standard [79]
    7. Niacin extended release+lovastatin combination (Advicor®) now available [79]
    8. Advicor® should not be used as initial therapy unless lipid profile warrants it [27]
    9. Advicor® increases HDL 30%, reduces LDL 42%, triglycerides 44%, Lp(a) 22%
  11. Fluvastatin (Lescol®, Lescol® XL)
    1. 20-40mg po qhs or Lescol® XL 80mg po qhs
    2. Significantly lower price compared with others
    3. 20-25% LDL reduction with 20-40mg/d standard fluvastatin
    4. Lescol® XL 80mg/d provides >35% LDL and 25% triglyceride reduction, HDL increase 20%
    5. Fluvastatin after percutaneous coronary intervention in patients with average Chol reduced major cardiac events by >20% at 3.5 years [74]
  12. Cerivastatin (Baycol®) [9,64]
    1. 31 cases of fatal rhabdomyolysis reported (unclear mechanism)
    2. Withdrawn from market
  13. Contraindications
    1. Liver Disease and/or concurrent hepatotoxic agents
    2. Concurrent niacin or fibric acid therapy (high incidence of rhabdomyolysis)
    3. Caution with patients concurrently on immunosuppressive agents
    4. Only severe renal failure requires dose reduction
  14. Side Effects [40]
    1. Elevated Transaminases - AST and ALT (liver function tests, LFTs)
    2. Elevated transaminases have not been clearly linked to increased liver disease [40]
    3. Myopathy (see below)
    4. Statins have no effect on the risk of any kind of cancer [22,62]
    5. Very safe in general clinical practice
  15. Myopathy [23,80,84,96]
    1. Muscle pain and weakness affects 1-5% of persons
    2. Serious myopathy 0.44 cases per 10,000 person years [23]
    3. Fatal rhabdomyolysis is extremely rare (0.15 per 1 million prescriptions)
    4. Cerivastatin (Baycol®) was withdrawn from market due to higher myositis rates [64]
    5. Statins may also cause severe weakness with no increase in CPK levels [77]
    6. Mild creatinine phosphokinase (CPK) elevations may occur and should be followed closely
    7. Generally recommend discontinuation for CPK elevations >10X normal
    8. Concern with hypothyroidism, reduced renal or hepatic function, certain medications
    9. High lipophilicity, high doses, and drug-drug interaction potential correlate with risk
    10. Higher doses of statins associated with higher risk of myositis, rhabdomyolysis [96]
    11. Avoid concommitant gemfibrozil, cyclosporine, azole antifungals, macrolides, others
    12. Caution in combination with niacin - must monitor LFTs and CPK closely
    13. Patients on statins with new onset weakness should undergo muscle biopsy
  16. Monitoring: LFTs and CPK each month initially, then every 2-6 months
  17. Fluvastatin, cerivastatin, atorvastatin are most cost effective based on cost per % change in chol
  18. Pharmacogenetics of Response to Statins [17]
    1. Single nucleotide polymorphisms (SNPs) in HMG CoA reductase gene linked to response
    2. Prevalence of these SNPs is 6.7% and they are in 90% linkage disequilibrium
    3. Single copy (heterozygotes) of either of these SNPs associated with ~20% less chol reduction with pravastatin compared with major allele
  19. Long term compliance is very poor in elderly patients [75,76]

C. Niacin [1,12,13]navigator

  1. Indications [49]
    1. Major activity is reduction of triglycerides and increase in HDL
    2. Most effective agent for HDL elevation at 20-35% increases
    3. Raising HDL reduces progression of CV disease, may prevent CV events [26]
    4. Lowers VLDL/triglycerides >20%
    5. Modest LDL reduction ~8% (higher doses usually required)
    6. Indicated for elevated chol with high LDL and low HDL or high triglycerides
    7. Particularly useful in diabetics with low HDL and high triglycerides
    8. Slow release forms such as Niaspan® and Slo-Niacin are strongly recommended
  2. Efficacy [27]
    1. Effects are dose related, and target dose 1000mg tid is most effective
    2. Moderate doses (1.5gm/d) gave 20% increase in HDL levels and fairly well tolerated
    3. Reduces risk of second MI in patients with first MI and hypercholesterolemia
    4. Combination simvastatin + niacin more effective than simvastatin alone for secondary prevention of CV events in patients with normal LDL and low HDL [21]
    5. Niceritrol (nicotonic acid derivative, 750-1500mg/d) reduced levels of LDL chol, Lp(a) and urinary protein loss over 12 months in patients with CRF [82]
  3. Dosing
    1. Initially 100mg tid, increase gradually to maximal 1000mg tid
    2. Sustained release (SR) forms better tolerated than immediate but more hepatitis
    3. SR forms reduce triglycerides better; IR forms increase HDL better
    4. Niacin extended release (Niaspan®) 2000mg taken qpm is well tolerated
    5. Monitor liver function tests (LFTs) and muscle (creatine kinase, CK) q1-2 months
    6. May be combined with simvastatin or other statins; frequent monitoring required
  4. Side Effects
    1. Flushing, pruritus; relieved by taking one aspirin prior to each dose
    2. Elevated LFTs: more common with slow release forms
    3. Blurred vision, glucose intolerance, hyperuricemia
    4. Fulminant hepatic failure (very uncommon)
    5. Myositis is uncommon alone but frequent with concommitant use of HMG Agent
    6. Discontinuation in ~42% of persons taking niacin within 5 years from side effects
  5. Relative Contraindications
    1. Peptic ulcer disease
    2. Acute gout
    3. Diabetes mellitus is not a contraindication; niacin is very effective in this setting [49]
  6. Absolute Contraindications
    1. Active liver disease
    2. Alcohol abuse
    3. Active Peptic ulcer disease
  7. Overall, highly effective, but statins better tolerated and reduce LDL more [13]

D. Chol Absorption Inhibitor [43,79]navigator

  1. Ezetimibe (Zetia®) is a novel agent which blocks chol absorption from gut
  2. Dose: 10mg po qd
  3. May be used alone or in combination with statins
  4. Reduces total and LDL chol by ~21%, and Apo B levels
  5. Adding to statin is more effective than doubling dose of statin
  6. If used with bile acid sequestrant, give >2 hours before or >4 hours after sequestrant
  7. Do not use in patients with moderate to severe hepatic insufficiency
  8. Unclear if reduces CV events similar to statins
  9. Vytorin®, combined ezetimibe and simvastatin, reduces chol better than either alone [95]

E. Bile Acid Sequestrantsnavigator

  1. Agents
    1. Colesevelam is a newer agent with improved pharmacology
    2. Cholestyramine is the major agent in the USA
    3. Colestipol is less commonly prescribed in the USA
  2. Mechanism
    1. Not absorbed from gastrointestinal tract
    2. Binds bile acids and interrupts enterhepatic bile acid circulation
    3. This increases conversion of chol to bile acids by liver
    4. Liver increases uptake of circulating LDL chol to make more bile acids
  3. Clinical Utility
    1. Reduce in coronary events when bile acids combined with dietary therapy
    2. Reduce total chol and improve TChol:HDL ratio
  4. Colesevelam (Welchol®) [50]
    1. Dose is 3.75 grams once or divided twice daily (available as 625mg tablets)
    2. Reduces LDL chol ~20%, raises HDL ~10%, without affecting triglycerides
    3. May be given concommitantly with statins leading to additive effects on chol levels
    4. Unlike other agents, does not affect intestinal absorption of fat soluble vitamins
    5. Combination with simvastatin is effective and well tolerated (reduces LDL 42%) [60]
    6. Colesevelam is the drug of choice in this category
    7. FDA approved as adjunct to diet and exercise for treatment of type 2 DM [112]
  5. Cholestyramine (Questran®, Prevalite®)
    1. 1-2 packets per meal, qd-tid po
    2. Must be given with psyllium (Metamucil) to prevent constipation
  6. Colestipol (Colestid®)
    1. Dose: 5-10mg tid with meals
    2. 2.5gm colestipol + 2.5gm Metamucil (psyllium) was effective and well tolerated
  7. Side Effects of all Bile Sequestrants
    1. Flatulence
    2. Constipation occurs in ~30% of users which is relieved with fiber (metamucil)
    3. Cholestyramine and colestipol inhibit intestinal absorption of fat soluble vitamins A,D,E,K
    4. Cholestyramine and colestipol also inhibit absorption of many other drugs
  8. Cholestyramine may also decrease pruritus due to hyperbilirubinemia in liver failure

F. Fibric Acids and PPAR-alpha Agonists [1,2,13,29]navigator

  1. Agents
    1. Gemfibrozil (Lopid®) - most commonly used fibric acid in USA
    2. Clofibrate (Atromid-S®) - high rate of side effects, increased severe gallstones
    3. Fenofibrate (TriCor®) - overall fairly well tolerated, highly potent [29]
    4. Bezafibrate (Bezalip®) - not available in USA; reduced coronary events
  2. Actions of Fibrates
    1. Modest reductions in total LDL and total chol
    2. Increase HDL 10-25%
    3. Reduce Triglycerides - 20-30% at highest doses for older drugs; ~50% for fenofibrate
    4. Reduce VLDL by reducing hepatic secretion of VLDL (carries triglycerides)
    5. May shift pattern of LDL chol to less atherogenic forms of LDL chol
    6. Gemfibrozil reduces coronary events beyond increases in HDL levels [57]
    7. Fenofibrate improves all chol levels and reduces angiographic atherosclerosis progression [58]
    8. Fenofibrate 200mg qd reduced total CV events in patients with diabetes not on another lipid-lowering therapy [99]
  3. Mechanisms of Action [37]
    1. Activate nuclear transcription factor called PPAR alpha (PPAR-a)
    2. PPAR-a is peroxisome proliferator-activated receptor
    3. PPAR-a stimulates transcription of LDL cholesterol and ApoAI genes
    4. PPAR-a also suppresses the expression of the Apo CII gene
    5. Fibrates are weak agonists of PPAR-a
    6. Stimulating PPAR-a results in reduced secretion of triglyceride-rich lipid particles
    7. Increase lipoprotein lipase activity and trigylceride clearance
  4. Indications
    1. Mainly useful for patients with high triglyceride levels
    2. Also for Type 2b dyslipidemia: triad high LDL, low HDL, high triglycerides
    3. Useful for patients with low HDL and high triglycerides (normal LDL)
    4. Gemfibrozil and clofibrate reduced primary incidence of heart disease in men
    5. Gemfibrozil reduced initial CV event or stroke by ~20% in patients with CAD who had normal LDL (<140mg/dL) but low HDL <40mg/dL [39]
    6. Strongly consider gemfibrozil in men with CAD and low HDL with normal LDL [39]
  5. Dosing
    1. Gemfibrozil 600mg bid po
    2. Fenofibrate 67mg po qd initially, increasing q4-8 weeks by 67mg to 200mg qd po max
    3. Clofibrate may increase mortality and is not recommended
  6. Side Effects
    1. Gemfibrozil: nausea, vomiting, possibly gallstones
    2. Fenofibrate: skin rash, flu-like symptoms, mild hepatitis (~5%), possibly gallstones
    3. Fenofibrate can increase serum creatinine and CK (creatinine phosphokinase) levels [44]
    4. All fibrates increase potency of anticoagulant warfarin
    5. All fibrates increase risk of rhabdomyolysis with statins and should not be combined
  7. No benefit of gemfibrozil when added to pravastatin + niacin therapy
    1. In addition, there is concern for increased hepatitis and myositis
    2. Combination therapy with fibrates should be used cautiously with careful monitoring
  8. Fenofibrate indicated for patients with triglycerides >500mg/dL
    1. Atorvastatin (Lipitor®) reduces triglycerides as much as older fibrates and is safer [7]
    2. However, atorvastatin 10-20mg/d reduced triglycerides less than fenofibrate [29]
    3. Fenofibrate is generally well tolerated, particularly micronized form
    4. Fenofibrate 200mg/day given to type 2 DM patients reduced diabetic retinopathy and need for retinal laser treatment ~35% [106]
  9. LY518674, a pure potent PPAR-a agonist, increases HDL-C and decreases triglycerides similar to fenofibrate, but can increases LDL-C levels and increases creatinine levels [44]

G. Cholesteryl Ester Transfer Protein (CETP) Inhibitors [30,89]navigator

  1. CETP mediates transfer of cholesteryl esters from HDL to apo(B) containing lipoproteins
  2. Torcetrapid
    1. Selective CETP inhibitor which increases HDL levels
    2. Increases HDL levels 46% alone or 61% when added to 20mg atorvastatin
    3. Reduces LDL by ~20% when added to atorvastatin compared with statin alone
    4. Despite changes in HDL and LDL, torcetrapib did not reduce intracoronary [30] or carotid [38] atheromata when added to atorvastatin
    5. Despite increases in HDL by 30mg/dL and reductions in LDL, torcetrapib added to atorvastatin did not reduce carotid atherosclerosis in familial hypercholesterolemia [32]
    6. Torcetrapib caused significant blood pressure increases ~5mm more than placebo [30,38]
    7. After 12 months, significantly increased risk of systolic blood pressure, CV events and death; corelated with reduced potassium and elevated bicarbonate and aldosterone [107]
  3. Anacetrapib [109]
    1. Oral potent, selective CETP inhibitor which increases HDL levels
    2. Up to ~30% increase in HDL with 38% reduction in LDL
    3. No effect on blood pressure at day 10 of dosing

H. Omega-3 Fatty Acids [92,102]navigator

  1. Primarily derived from fish oils
  2. Highly concentrated omega-3 polyunsaturated fatty acid preparation (Omacor®)
  3. FDA approved for treatment of very high(>500mg/dL) plasma triglycerides
  4. Combined esters of eicosapentaenoic and docosahexaenoic acids
  5. 20-50% reduction in triglycerides
  6. May be safely combined with with statins (no increase in side effects)
  7. May decrease risk of cardiac death after myocardial infarction
  8. Pro-arrhythmic effects may be present
  9. No clear benefits in healthy people
  10. Dose is 4gm daily (either once daily or 2gm bid)

I. Dietary Changes navigator

  1. Reducing trans-fatty acids and saturated fats leads to ~10% chol reduction [34]
  2. Adding omega-3 fatty acids improves profile [69]
  3. Increasing soluble dietary fiber improves lipid profile
  4. Cholesterol-lowering margerines (plant sterols) are now available [36]
  5. Sitostanol and sitosterol are major plant sterols [36]
  6. Plant sterols lower LDL and total cholesterol ~12% [36]
  7. Policosanol, a mixture of sugar cane wax derived alcohols, has no effect on lipids [101]
  8. Anti-oxidant vitamins C + E + ß-carotene had no effect on CAD associated events [15]

Resources navigator

calcLDL Cholesterol

References navigator

  1. Choice of Lipid-Regulating Drugs. 2001. Med Let. 43(1105):43 abstract
  2. Jacobson TA. 2000. Ann Intern Med. 133(7):549 abstract
  3. CHolesterol Treatment Trialists' Collaborators. 2008. Lancet. 371(9607):117
  4. Go AS, Iribarren C, Chandra M, et al. 2006. Ann Intern Med. 144(4):229 abstract
  5. Cholesterol Treatment Trialists Collaborators. 2005. Lancet. 366(9493):1267 abstract
  6. Mittleman MA. 2006. JAMA. 296(3):319 (Case Discussion) abstract
  7. Atorvastatin. 1997. Med Let. 39(997):29 abstract
  8. Hayward RA, Hofer TP, Vijan S. 2006. Ann Intern Med. 145(7):520 abstract
  9. Cerivastatin. 1998. Med Let. 40(1018):13 abstract
  10. Ridker PM, Cannon CP, Morrow D, et al. 2005. NEJM. 352(1):20 abstract
  11. Nissen SE, Tuzcu EM, Schoenhagen P, et al. 2005. NEJM. 352(1):29 abstract
  12. Niacin. 1993. Med Let. 35(891):20
  13. Ashen MD and Blumenthal RS. 2005. NEJM. 353(12):1252 (Case Discussion) abstract
  14. Balk EM, Lau J, Goudas LC, et al. 2003. Ann Intern Med. 139(8):670 abstract
  15. Heart Protection Study Collaborative Group. 2002. Lancet. 360(9326):23 abstract
  16. Crouse JR III, Raichlen JS, Riley WA, et al. 2007. JAMA. 297(12):1344 abstract
  17. Chasman DI, Posada D, Subrahmanyan L, et al. 2004. JAMA. 291(23):2821 abstract
  18. Heart Protection Study Collaborative Group. 2002. Lancet. 360(9326):7 abstract
  19. LaRosa JC, Grundy SM, Waters DD, et al. 2005. NEJM. 352(14):1425 abstract
  20. Nakamura H, Arakawa K, Itakura H, et al. 2006. Lancet. 368(9542):1155 abstract
  21. Brown BG, Zhao XQ, Chait A, et al. 2001. NEJM. 345(22):1583 abstract
  22. Dale KM, Coleman CI, Henyan NN, et al. 2006. JAMA. 295(1):74 abstract
  23. Graham DJ, Staffa JA, Shatin D, et al. 2004. Ann Intern Med. 292(21):2585 abstract
  24. Statins for High Risk Patients. 2006. Med Let. 48(1225):1 abstract
  25. Nissen SE, Nicholls SJ, Spiahi I, et al. 2006. JAMA. 295(13):1556 abstract
  26. Whitney EJ, Krasuski RA, Personius BE, et al. 2005. Ann Intern Med. 142(2):95 abstract
  27. Brunzell JD. 2007. NEJM. 370(10):1009
  28. Nicholls SJ, Tuzcu EM, Sipahi I, et al 2007. JAMA. 297(5):499 abstract
  29. Fenofibrate. 1998. Med Let. 40(1030):68 abstract
  30. Nissen SE, Tardif JC, Nicholls SJ, et al. 2007. NEJM. 356(13):1304 abstract
  31. SPARCL Investigators. 2006. NEJM. 355(6):549 abstract
  32. Kastelein JJ, van Leuven S, Burgess L, et al. 2007. NEJM. 356(16):1620 abstract
  33. Stein EA, Illingworth DR, Kiwterovich PO Jr. 1999. JAMA. 281(2):137 abstract
  34. Lichtenstein AH, Ausman LM, Jalbert SM, Schaefer EJ. 1999. NEJM. 340(25):1933 abstract
  35. Rosuvastatin. 2003. Med Let. 45(1167):81 abstract
  36. Cholesterol-Lowering Margerines. 1999. Med Let. 41(1055):56 abstract
  37. Yki-Jarvinen H. 2004. NEJM. 351(11):1106 abstract
  38. Bots ML, Visseren FL, Evans GW, et al. 2007. Lancet. 370(9582):153 abstract
  39. Rubins HB, Robbins SJ, Collins D, et al. 1999. NEJM. 341(6):410 abstract
  40. Armitage J. 2007. Lancet. 370(9601):1781 abstract
  41. Fathi R, Haluska B, Short L, Marwick TH. 2003. Am J Med. 114(6):445 abstract
  42. LaCroix AZ, Cauley JA, Pettinger M, et al. 2003. Ann Intern Med. 139(2):97 abstract
  43. Gagne C, Bays HE, Weiss SR, et al. 2002. Am J Cardiol. 90:1084 abstract
  44. Nissen SE, Nicholls SJ, Wolski K, et al. 2007. JAMA. 297(12):1362 abstract
  45. Lee TH, Cleeman JJ, Grundy SM, et al. 2000. JAMA. 283(1):94 abstract
  46. Khwaja A, Connolly JO, Hendry BM. 2000. Lancet. 355(9205):741 abstract
  47. Chan KA, Andrade SE, Boles M, et al. 2000. Lancet. 355(9222):2185 abstract
  48. White HD, Simes RJ, Anderson NE, et al. 2000. NEJM. 343(5):317 abstract
  49. Elam MB, Hunninghake DB, Davis KB, et al. 2000. JAMA. 284(10):1263 abstract
  50. Colesevelam. 2000. Med Let. 42(1091):103
  51. Jick H, Zornberg GL, Jick SS, et al. 2000. Lancet. 356(9242):1627 abstract
  52. Tonkin AM, Colquhoun D, Emberson J, et al. 2000. Lancet. 356(9245):1871 abstract
  53. Stenestrand U and Wallentin L. 2001. JAMA. 285(4):430 abstract
  54. Psaty BM, Smith NL, Lemaitre RN, et al. 2001. JAMA. 285(7):906 abstract
  55. Reid IR, Hague W, Emberson J, et al. 2001. Lancet. 357(9255):509 abstract
  56. Smilde TJ, van Wissen S, Wollersheim H, et al. 2001. Lancet. 357(9256):577 abstract
  57. Robins SJ, Collins D, Wittes JT, et al. 2001. JAMA. 285(12):1585 abstract
  58. Diabetes Atherosclerosis Intervention Study Investigators. 2001. Lancet. 357(9260):905 abstract
  59. Schwartz GG, Olsson AG, Ezekowitz MD, et al. 2001. JAMA. 285(13):1711 abstract
  60. Knapp HH, Schrott H, Ma P, et al. 2001. Am J Med. 110(5):352 abstract
  61. Hunt D, Young P, Simes J, et al. 2001. Ann Intern Med. 134(10):931 abstract
  62. Bjerre LM and LeLorier J. 2001. Am J Med. 110(9):716 abstract
  63. Andrews TC, Ballantyne CM, Hsia JA, Kramer JH. 2001. Am J Med. 111(3):185 abstract
  64. Substituting for Cerivastatin (Baycol). 2001. Med Let. 43(1113):79 abstract
  65. Frenette PS. 2001. NEJM. 345(19):1419 abstract
  66. Mondillo S, Ballo P, Barbati R, et al. 2003. 114(5):359 abstract
  67. Mulder HJ, Bal ET, Jukema JW, et al. 2000. Am J Cardiol. 86(7):742 abstract
  68. Walter DH, Schachinger V, Elsner M, et al. 2000. Am J Cardiol. 85(8):962 abstract
  69. Jula A, Marniemi J, Huupponen R, et al. 2002. JAMA. 287(5):598 abstract
  70. Pasco JA, Kotowicz MA, Henry MJ, et al. 2002. Arch Intern Med. 162:537 abstract
  71. Herrington DM, Howard TD, Hawkins GA, et al. 2002. NEJM. 346(13):967 abstract
  72. LIPID Study Group. 2002. Lancet. 359(9315):1379 abstract
  73. Newby LK, Kritinsson A, Bhapkar MV, et al. 2002. JAMA. 287(23):3087 abstract
  74. Serruys PWJC, de Feyter P, Macaya C, et al. 2002. JAMA. 287(24):3215 abstract
  75. Benner JS, Glynn RJ, Mogun H, et al. 2002. JAMA. 288(4):455 abstract
  76. Jackevicius CA, Mamdani M, Tu JV. 2002. JAMA. 288(4):462 abstract
  77. Phillips PS, Haas RH, Bannykh S, et al. 2002. Ann Intern Med. 137(7):581 abstract
  78. Tonelli M, Moye L, Sacks FM, et al. 2003. Ann Intern Med. 138(2):98 abstract
  79. New Drugs for Hyperlipidemia. 2003. Med Let. 45(1151):17 abstract
  80. Thompson PD, Clarkson P, Karas RH. 2003. JAMA. 289(13):1681 abstract
  81. Sever PS, Dahlof B, Poulter NR, et al. 2003. Lancet. 361(9364):1149 abstract
  82. Owada A, Suda S, Hata T. 2003. Am J Med. 114(5):347 abstract
  83. Nissen SE, Tuzcu EM, Schoenhagen P, et al. 2004. JAMA. 291(9):1071 abstract
  84. Rosenson RS. 2004. Am J Med. 116(6):408 abstract
  85. Heart Protection Study Collaborative Group. 2004. Lancet. 363(9411):757 abstract
  86. Snow V, Aronson MD, Hornbake ER, et al. 2004. Ann Intern Med. 140(8):644 abstract
  87. Vigan S and Hayward RA. 2004. Ann Intern Med. 140(8):650 abstract
  88. Cannon CP, Braunwald E, McCabe CH, et al. 2004. NEJM. 350(15):1495 abstract
  89. Brousseau ME, Schaefer EJ, WOlfe ML, et al. 2004. NEJM. 350(15):1505 abstract
  90. Spencer FA, Allegrone J, Goldberg RJ, et al. 2004. Ann Intern Med. 140(11):857 abstract
  91. Cholesterol Rethink for High Risk Patients. 2004. Med Let. 46(1182):37 abstract
  92. Omega-3 Fatty Acids. 2005. Med Let. 47(1221):91 abstract
  93. McCarey DW, McInnes IB, Madhok R, et al. 2004. Lancet. 363(9426):2015 abstract
  94. Wiegman A, Hutten BA, de Groot E, et al. 2004. JAMA. 292(3):331 abstract
  95. Vytorin. 2004. Med Let. 46(1191):73 abstract
  96. Aggressive Statin Therapy. 2004. Med Let. 46(1196):93 abstract
  97. Goldberg AC, Sapre A, Liu J, et al. 2004. Mayo Clin Proc. 79:620 abstract
  98. Pedersen TR, Faergeman O, Kastelein JJ, et al. 2005. JAMA. 294(19):2437 abstract
  99. FIELD Study Investigators. 2005. Lancet. 366(9500):1849 abstract
  100. Briel M, Schwartz GG, Thompson PL, et al. 2006. JAMA. 295(17):2046 abstract
  101. Berthold HK, Unverdorben S, Degenhardt R, et al. 2006. JAMA. 295(19):2262 abstract
  102. Fish Oil Supplements. 2006. Med Let. 48(1239):59 abstract
  103. Go AS, Lee WY, Yang J, et al. 2006. JAMA. 296(17):2105 abstract
  104. Wenger NK, Lewis SJ, Herrington DM, et al. 2007. Ann Intern Med. 147(1):1 abstract
  105. Ford I, Murray H, Packard CJ, et al. 2007. NEJM. 257(15):1477
  106. Keech AC, Mitchell P, Summanen PA, et al. 2007. Lancet. 370(9600):1687 abstract
  107. Barter PJ, Caulfield M, Eriksson M, et al. 2007. NEJM. 357(21):2109 abstract
  108. Kjekshus J, Apetrei E, Barrios V, et al. 2007. NEJM. 357(22):2248 abstract
  109. Krishna R, Anderson MS, Bergman AJ, etal. 2007. Lancet. 370(9603):1907 abstract
  110. Niacin/Simvastatin Combination. 2008. Med Let. 50(1283):25 abstract
  111. Which Statin? 2008. Med Let. 50(1284):29 abstract
  112. Coesevelam. 2008. Med Let. 50(1285):33