Lipid Lowering therapy

Question 1

Lipid transport

Answer 1

Lipoproteins
LDL liver to peripheral tissues, adverse effects
HDL takes lipids from periphery to liver, beneficial
(Triglycerides; adverse vascular effects, pancreatitis)

Question 2

Why lower cholesterol?

Answer 2

Primary prevention: debated, reduction in vascular events

Secondary: Large benefit, after MI for example. Decreases CVS mortality and morbidity. Will reduce vascular events

Question 3

Who to treat with LLT?

Answer 3

Secondary prevention: Angina, MI, CVA, PVD
Diabetes (high vascular risk)
Primary prevention: 10 year CV risk score >30%

Question 4

Ways to lower cholesterol

Answer 4

Drugs and lifestyle

Question 5

Drugs to lower lipids

Answer 5

Statins: Lower Chol and LDL, slighty raise HDL, and lower trigs. Atorvastatin (more effective) and simvastatin
Fibrates: lower trigs and raise HDL
Ezetimibe: lowerTC and LDL
Nicotinic acid: lower trigs

Question 6

Statin mechanism of action

when to give

Answer 6

1) Inhibit HMG CoA reductase, which normally converts HMG CoA to Mevalonate, eventually cholesterol. (In hepatocytes)
2) Secondary to this, as hepatocytes need cholesterol for bile acids etc, they up regulate LDL receptors, lowering circulating LDL

At night

Question 7

What else do statins lower? Effect?

Answer 7

Isoprenoids, involved with things such as apoptosis.

So called theorised pleiotropic efect, where lowering these can be anti-thrombotic, anti inflammatory and immune modulators

Question 8

Where is simvastatin metabolised? Consequence and do no prescribe with?

Answer 8

CYP3A4 in the liver P450 system. Atorvastatin not so bad
So do not prescribe with enzyme inhibitors, as prolong effects, increase side effects.
Do not with amiodarone, verapamil, diltiazem, erythromycin

Question 9

Statin side effects

Answer 9

Myalgias
Myositis
Rhabdomyolysis
deranged LFT's, stop if ALT 3x normal
Are teratogenic
Very rare, prolonged exposure, new diabetes

Question 10

effect on CV risk with statin use according to a meta analysis

Answer 10

per mmol/L reduction in LDL

total mortality dow 12% and vascular events down 21%

Question 11

What do fibrates do and indications

Mechansim

Answer 11

Lower trigs, lower LDL an raise HDL

• Isolated triglyceridaemia (lifestyle first) as high triglycerides can induce a pancreatitis
• Combined with statins with resistant hypercholesterolaemia

Mechanism: PPARalpha agonist. A nuclear receptor that will alter lipid metabolism in liver and muscle, lowering VLDL and increase msucle FA storage. Also activate lipoprotein lipase to break down TG’s

Question 12

Fibrate side effects

Answer 12

GI upset, deranged LFT’s, concurrent statin use increases likelihood of myositis

Question 13

Ezetimibe

Answer 13

With statin, lower cholesterol absorption, so less cholesterol delivered to liver, increases LDL receptors in liver, lowers circulating LDL

Blocks NPC1L1 co-transport in enterocyte

Bit of diarrhoea

Question 14

Nicotinic acid

Answer 14

LowersTrigs synthesis in liver.

reduces FA mobilisation from periphery, reduced HDL degradation

Question 15

Lipid lowering therapy conclusions

Answer 15

• Secondary prevention definitely statins
• Primary, lifestyle best, statin use questionable, less than secondary
• Linear relationship CV events and TGs

Question 16

PSK9 inhibition

Answer 16

Is a circulating serine protease, that is endocytosed with LDL receptor. These will if blocked, decreases LDL

MAB evolocumab
RNA inhibitor inclisiran