Treatment of Dyslipidemias

Question 1

Indications for statin therapy

Answer 1

1. Secondary prevention in patients with clinical ASCVD [high intensity]
2. LDL > 190 mg/dL (Age > 21) [high intensity]
3. Primary Prevention: Diabetes + LDL 70-189 mg/dL (Age 40-75) [high intensity]
4. Primary Prevention: No Diabetes, 10 year ASCVD risk > 7.5%, LDL 70-189 mg/dL (Age 40-75) [mod intensity]

Question 2

Efficacy of statin therapy by intensity of treatment

Answer 2

High intensity statin therapy - lowers LDL by ~50%

Moderate-intensity statin therapy - lowers LDL by 30-50%

Low intensity statin therapy - lowers LDL < 30%

Question 3

Statins - Mechanism

Answer 3

Inhibits HMG CoA reductase; primary means by which LDL is lowered is by an increase in the number of intra-hepatic LDL receptors, which increases uptake and catabolism of circulating LDL

Question 4

Statins - Adverse Effects

Answer 4

Myopathy - myalgias, elevated CPK (10%)

Elevated LFTs

Rhabdomyolysis

New onset T2DM (10%) - increased risk with pre-existing glucose intolerance or a positive family history of T2DM

Question 5

Bile acid sequestrants - Mechanism, efficacy, adverse effects

Answer 5

High molecular weight polymers bind to bile acids in the intestine, reducing enterohepatic recirculation and intra-hepatic cholesterol pool; this increases hepatic LDL-R, which increases clearance of circulating LDL by 10-30%

Adverse effects: Nausea, bloating, constipation

Question 6

Ezetimibe

Answer 6

Selectively inhibits cholesterol absorption; reduces circulating cholesterol by 15-20%

No side effects

Question 7

Plant sterol / stanol esters

Answer 7

Prevent micelle formation, reducing absorption of cholesterol; lowers circulating LDL by 5-10%

No side effects

Question 8

Drug classes indicated for lowering LDL

Answer 8

Statins
Bile Acid Sequestrants
Ezetimibe
Plant sterols / stanols

Question 9

Fibrates - Mechanism, efficacy

Answer 9

Increases PPAR-a mediated gene expression, causing increased hepatic fatty acid oxidation and reduced synthesis and secretion of TG-rich VLDLs from the liver

Reduces TG by 20-40% and increases HDL by 5-15%

Question 10

Fish Oil - Mechanism, Dosing

Answer 10

High dose omega 3 fatty acids (EPA, DHA) in doses of 3-4 grams reduce TG levels by 15-35% via a reduction in hepatic VLDL synthesis

Question 11

Drug classes used to lower TGs

Answer 11

Fibrates

Fish oil

Question 12

Drug classes used to treat combination hyperlipidemia

Answer 12

1. High intensity statins - lower LDL and TGs

2. Niacin - lowers LDL and TGs, increases HDL

Question 13

Niacin

Answer 13

Lowers TGs and LDL and increases HDL in the setting of combined hyperlipidemia; question if addition as add-on to statin therapy provides extra benefit

Adverse effects: Flushing, GI distress, liver/kidney damage, myopathy, glucose intolerance, uricemia/Gout