Treatment of Dyslipidemias

Question 1

Which statins for which benefit groups?

Answer 1

1. Clinical ASCVD - high intensity
2. LDL > 190 - high intensity
3. Primary prevention with diabetes - moderate or high
4. Primary prevention without diabetes - moderate intensity

Question 2

Mechanism of statin action

Answer 2

1. Inhibit HMG CoA reductase
2. Decrease hepatic pool of free cholesterol
3. Increase expression of LDL receptors on cell membranes
4. Increase catabolism of VLDL and LDL
5. Decrease LDL-C concentrations

Question 3

6% rule

Answer 3

With each statin dose doubling, only get a 6% fall in LDL

Question 4

The down sides of statins

Answer 4

1. Abnormal AST and ALT
2. Myopathy (myalgias, myositis, rhabdo)
3. Cognitive impairment
4. New onset T2DM (if you get this, you were probably already at risk for it)

Question 5

Other mechanisms to lower LDL via gut

Answer 5

1. BAS (bind bile acids and interferes with their ability to be reabsorbed, makes liver use cholesterol to make more bile acids - cholestyramine, cholestipol, colesevelam)
2. Plant stanols (inhibition of cholesterol absorption)
3. Ezetimibe (selective cholesterol absorption inhibitors)

Question 6

Effect of reduced cholesterol content of hepatic cells

Answer 6

1. Stimulates increased cholesterol synthesis

2. Stimulates LDL receptor synthesis and LDL uptake by the liver

Question 7

Contraindications to BAS

Answer 7

1. Elevated TG
2. Dysbetalipoproteinemia

Side effects are all GI related (mouth sensation, bloating, nausea, constipation, anal irritation)

Question 8

Ezetimibe

Answer 8

1. Blocks cholesterol absorption at the intestinal brush border
2. Binds to neimann-pick C1 like 1 (NPC1L1) and blocks cholesterol absorption by inhibiting NPC1L1 from incorporating into the clathrin coated vesicles
3. No effect on absorption of fat soluble vitamins

Minimal systemic exposure, NO adverse effects

Question 9

Plannt sterol and Stanol Esters

Answer 9

1. OTC
2. Low absorption
3. Dose 2-3 g/day
4. Reduce LDL by 5-10%
5. May interfere with absorption of lipid soluble vitamins

Not suggested with BAS because it reduces effect of BAS, and very mild lowering

Question 10

PCSK9 Adverse Events

Answer 10

1. Injection site reactions
2. Drug induced antibodies
3. Allergy
4. Neurocognitive events (cognition impaired?)