Dyslipidemia (high levels of lipids)

Question 1

HMG-CoA Reductase Inhibitors

MOA (5) & SE (4)

Answer 1

Statins:

Indications: The BEST at lowering cardiac Risk.

Mechanism of action: inhibit the rate-limiting step of cholesterol synthesis in the liver –> < hepatic free cholesterol pool, up-regulation of LDL receptors, > uptake of LDL by the liver, the most significant < plasma LDL levels.

Side effects: The most common side effect is elevated liver enzymes, also myositis, myalgia do occur, and rhabdomyolysis (rare/high doses).

Question 2

Niacin

MOA & SE (4)

Answer 2

A vitamin B that has to be given in 100-300 times its dose as a vitamin to < LDL, < TG, and > HDL (Dose: >3g/day)

Unknown mechanism of action (<VLDL synthesis, >LPLase activity)

SE: Flushing: major side-effect (< by pretreating with ASA, and SR forms)
Other side-effects: vasodilation (may potentiate antihypertensives), diarrhea, drug-induced hepatitis.

Question 3

Bile Acid Sequestrants (Resins)

MOA & SE (5)

Answer 3

Cholestyramine (Questran®) (4-16g/d) & colesevelam (Welchol®) (3.75g/d) [should be taken before meals]

Act to bind bile acids in the intestines, forming an insoluble complex that is excreted in the feces.
This decreases the return of cholesterol to the liver, the latter will respond by up-regulating the LDL receptors, which > the plasma LDL uptake by the liver.

SE: flatulence, bloating, constipation, >TG, bind other medications and < their absorption and bioavailability [oral anticoagulants, thyroid hormones, digoxin, penicillins, tetracyclins]. [take concomitant medications at least 1 hour before or 4 hours after the bile aid resins]

Question 4

Fibric Acid Derivatives

MOA & SE (2)

Answer 4

Gemfibrozil (Lopid®), fenofibrate (TriCor®).

Indication: severe hypertriglyceridemia >500 (NOT for high cholesterol)

Mechanism of action: stimulation of lipoprotein lipase, promoting catabolism of VLDL & TG.

SE: gall stones, LFT abnormalities.

If patient is using Statins, DON’T use Gemfibrozil (> risk of myalgia (muscle pain), use fenofibrate causes less muscle pain).

Question 5

Omega-3 Fatty Acids (Fish Oils)
DHA & EPA

MOA & SE (4)

Answer 5

4G QD.

Indications: Hypertriglyceridemia.

MOA is not currently known, end result = < TG synthesis by the liver.

SE: Fishy burps (put in fridge or freezer), > LDL, Bleed Risk (avoid: warfarin, NSAIDS, ASA), GI upset (take w/ food).

Question 6

Cholesterol Absorption Inhibitors

MOA & contraindications

Answer 6

ezetimibe (Zetia®)

Indications: This is the 1st Add-on drug to consider with Statins. Usually given with statins to further lower the LDL levels using lower doses of statins.

MOA: inhibits cholesterol absorption from small intestine, thus < the hepatic free cholesterol pool.

Contraindications: moderate to severe hepatic insufficiency

Question 7

ACL Inhibitors

MOA & SE

Answer 7

Bempedoic Acid (Nexletol®)

Indications: This is 2nd Add-on Drug to consider w/ Statins. Tx of hypercholesterolemia in adults with familial hypercholesterolemia or with established ASCVD who need additional lowering of LDL. Administered orally in combination with diet and the highest tolerated statin therapy.

MOA: Inhibits ATP citrate lyase enzyme, which is involved in the liver’s biosynthesis of cholesterol (upstream of HMG-CoA reductase).

Side effects: Muscle spasms, gout, diarrhea

Question 8

PCSK9 Inhibitors

MOA & SE

Answer 8

Evolocumab (Repatha®) & Alirocumab (Praluent®): Every 2 weeks or once monthly as SC injection

Indications: 3rd Add-on drug to consider. Usually given with statins to further lower the LDL levels in patients with familial hypercholesterolemia or whenever maximally tolerated statin therapy is not sufficient to control LDL-C levels in “Very High Risk” ASCVD patients.

MOA: Monoclonal antibodies that inhibit PCSK9, which LOWERS plasma LDL-C levels THE MOST.

Side effects: Injection site reaction, “flu” like symptoms, nausea, fatigue, diarrhea, might result in increased blood sugar levels.

Question 9

High-Intensity Statin Therapy

Answer 9

Lowers LDL-C by ≥ 50%

Atorvastatin 40-80 mg
Rosuvastatin 20-40 mg

Indications:
(1) Clinical Atherosclerotic Cardiovascular Disease (ASCVD)
(2) LDL ≥ 190
(3) Consider Diabetics, LDL 70 to 189, Age 50-75 OR w/ multiple risk factors
(4) Non-DM, Age 40-75, LDL 70-189 +10-Yr Risk ≥ 20%

Question 10

Moderate-Inensity Statin Therapy

Answer 10

Lowers LDL-C by 30% to 49%:

Atorvastatin 10 to 20 mg Rosuvastatin 5 to 10 mg
Simvastatin 40 mg
Pravastatin 40 mg
Lovastatin 40 mg

Indications:
(1) Diabetics, Age 40-75, LDL 70 to 189.
(2) Non-DM, Age 40-75, LDL 70-189 + 10-Yr Risk ≥ 7.5%

Question 11

Clinical
ASCVD

Answer 11

Brain: Stroke, TIA.

Heart: CAD with stable angina, Acute coronary syndrome (ACS), Coronary/arterial revascularization,

Vessels: Peripheral vascular disease (with or without claudication), Aortic aneurysm.

Tx: High-intensity statin

Question 12

Very High Risk of future ASCVD events

Answer 12

History of multiple major ASCVD events
OR
1 major ASCVD event and multiple high-risk conditions

Tx: High-intensity statin

If LDL-C remains ≥ 70
Add non-statin therapy:
Ezetimibe, ACL, then
PCSK9-I

Question 13

ASCVD high-risk Conditions

Answer 13

Age ≥ 65, Heterozygous Familial Hypercholesterolemia, Hx of CABG or prior stent/balloon, DM, HTN, Chronic Kidney Disease (GFR 15-59), Current Smoker, CHF, LDL ≥ 100 despite max Statin & ezetimibe.

Question 14

DM Risk Enhancers to consider High Intensity Statins.

Answer 14

Long duration (DM 2: >10 yrs or Dm1: > 20 yrs), Albuminuria >30 mcg, GFR <60, Retinopathy, Neuropathy, ABI < 0.9.