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HLD Tx & AHA/ACC GuidelinesMegan Chan, PGY-2UHCMC 2015
DrugEffect on LDL
Effect on
HDL
Effect on TG
Mechanism of Action Side Effects
HMG-CoA reductase inhibitors: “Statins”
↓↓↓ ↑ ↓
Inhibits rate limiting step of cholesterol precursor formation
HepatotoxicityRhabdomyolysis (esp in combo with fibrates & niacin)
Niacin (Vit B3)
↓↓ ↑↑ ↓
Inhibits lipolysis in adipose tissue; Reduces hepatic VLDL synthesis
Flushed face (vasodilation, ↓ w/ ASA) Hyperglycemia (↑ insulin resistance)Hyperuricemia
Bile acid resins: CholestyramineColestipolColesvelam
↓↓ Slight ↑
Slight ↑
Prevents intestinal reabsorption of bile acids; livers uses cholesterol to make more
Bad tasteGI upset↓ absorption of fat-soluble vitaminsCholesterol gallstones
Cholesterol absorption blockers:Ezetimibe
↓↓ -- --
Prevents cholesterol absorption in small intestine
Rare ↑ LFTsDiarrhea
Fibrates:GemfiborzilFenofibrateClofibrate
↓ ↑ ↓↓↓
Upregulate LPL gene ↑ TG clearance
MyositisHepatotoxicityCholesterol gallstones (esp with bile acid resins)
DrugEffect on LDL
Effect on
HDL
Effect on TG
Mechanism of Action Side Effects
HMG-CoA reductase inhibitors: “Statins”
↓↓↓ ↑ ↓
Inhibits rate limiting step of cholesterol precursor formation
HepatotoxicityRhabdomyolysis (esp in combo with fibrates & niacin)
Niacin (Vit B3)
↓↓ ↑↑ ↓
Inhibits lipolysis in adipose tissue; Reduces hepatic VLDL synthesis
Flushed face (vasodilation, ↓ w/ ASA) Hyperglycemia (↑ insulin resistance)Hyperuricemia
Bile acid resins: CholestyramineColestipolColesvelam
↓↓ Slight ↑
Slight ↑
Prevents intestinal reabsorption of bile acids; livers uses cholesterol to make more
Bad tasteGI upset↓ absorption of fat-soluble vitaminsCholesterol gallstones
Cholesterol absorption blockers:Ezetimibe
↓↓ -- --
Prevents cholesterol absorption in small intestine
Rare ↑ LFTsDiarrhea
Fibrates:GemfiborzilFenofibrateClofibrate
↓ ↑ ↓↓↓
Upregulate LPL gene ↑ TG clearance
MyositisHepatotoxicityCholesterol gallstones (esp with bile acid resins)
https://classconnection.s3.amazonaws.com/121/flashcards/1042121/png/lipid_lowering_agents1364672904716.png
2013 AHA/AC
C Preventi
on Guidelin
es:
http://content.onlinejacc.org/article.aspx?articleid=1879710
2013 AHA/ACC Prevention Guidelines:
2013 AHA/AC
C Preventi
on Guidelin
es:
Framingham’s 10 year CV Risk Score• Online Calculator: http://cvdrisk.nhlbi.nih.gov/• Calculates patient’s risk of an MI in the next 10
years.• Low risk < 10%, Intermediate risk 10-20%,
High risk >20%• Factors:• Age• Gender• Total Cholesterol• HDL Cholesterol• Smoker• Systolic BP• Taking any anti-hypertensive agents
High-Intensity Statin
Moderate-Intensity Statin
Low-Intensity Statin
Lowers LDL by ≥ 50%
Lowers LDL by 30% to <50%
Lowers LDL by <30%
Atorvastatin 40-80mgRosuvastatin 20-40mg
Atorvastatin 10-20mgRosuvastatin 5-10mgSimvastatin 20-40mgPravastatin 40-80mgLovastatin 40mgFluvastatin 40mg BID
Simvastatin 10mgPrvastatin 10-20mgLovastatin 20mg
Statin Interconversion
LDL Reduction
Atorvastatin
Lovastatin
Simvastatin
Pravastatin
Rosuvastatin
20-30% -- 20mg 10mg 20mg --
30-40% 10mg 40mg 20mg 40mg, 80mg
--
40-45% 20mg 80mg 40mg -- 5mg
45-50% 40mg -- -- -- 10mg
50-55% 80mg -- -- -- 20mg
55-60% -- -- -- -- 40mg
http://www.globalrph.com/statins
Follow Up:
2013 AHA/AC
C Preventi
on Guidelin
es
Secondary Causes of HLD
http://circ.ahajournals.org/content/129/25_suppl_2/S1/T8.expansion.html
Secondary Cause High LDL High TG
Diet Saturated fatsWeight gainAnorexia nervosa
Weight gainVery low fat dietsHigh carb dietsExcessive ETOH
Drugs DiureticsGlucocorticoidsAmiodaroneCyclosporine
Oral estrogens, tamoxifenGlucocorticoidsBile acid sequestrantsProtease inhibitorsBeta blockers (not carvedilol)Thiazides, Sirolimus
Diseases Nephrotic syndromeBiliary obstruction
Nephrotic syndromeChronic renal failureLipodystrophies
Disorders of altered states of metabolism
HypothyroidismObesityPregnancy
Uncontrolled DMHypothyroidismObesityPregnancy
References• First Aid• Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013
ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-934.
• Trevor AJ, Katzung BG, Kruidering-Hall M, et al. Katzung & Trevor’s Pharmacology Examination & Board Review, 10th ed. 2013. Mc Graw Hill. New York, NY.
• Wilson PW, D'agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837-47.