Lipids: Drugs and Therapy

What 5 lifestyle modifications reduce ASCVD risk?

Heart-healthy diet, physical activity, weight management, smoking cessation, and limiting alcohol.

What type of fat should patients reduce to help lower LDL-C and what should they avoid?

Saturated fat; avoid trans fat.

What 6 types of foods should patients increase?

Fruits, vegetables, whole grains, legumes, nuts, and fiber-rich foods.

What type of dietary fiber helps lower LDL-C?

Soluble fiber

How much moderate-intensity aerobic activity is commonly recommended weekly?

at least 150 minutes

Are lifestyle modifications recommended even when a patient starts a statin?

Yes

Are dietary supplements routinely recommended to lower LDL-C or TG and prevent ASCVD?

No. Evidence of clinical benefit is limted or inconsistent

What is the MOA for statins?

Inhibit HMG-CoA reductase → decrease hepatic cholesterol synthesis → increase LDL receptors → decrease LDL-C.

What is the primary effect of statins on the lipid panel?

It mainly decrease LDL-C; also decrease TG/VLDL and slightly increases HDL-C.

What are the 4 most important statin adverse effects?

Myalgia, myopathy, rare rhabdomyolysis, elevated liver enzymes.

What is the most common statin related possible muscle problem and the symptoms?

Myalgia: muscle aches, cramps, or weakness

What is the most serious but rare muscle-related adverse effect of statins? Include the symptoms.

Rhabdomyolysis: severe muscle pain or weakness, dark urine, possible kidney injury.

What lab value can be significantly elevated in rhabdomyolysis?

Creatine kinase (CK)

Which two statins are capable of high-intensity LDL-C lowering? Give generic&brand names.

Rosuvastatin (crestor) Atorvastatin (lipitor)

Which statins are relatively hydrophilic?

Pravastatin and Rosuvastatin

Which statins are more lipophilic?

Atorvastatin, simvastatin, lovastatin, fluvastatin, pitavastatin.

Which statins are particularly affected by CYP3A4 drug interactions?

Simvastatin, lovastatin, and atorvastatin.

What is the mechanism of action of ezetimibe?

Inhibits NPC1L1 in the small intestine, decreasing cholesterol absorption.

How does ezetimibe lower circulating LDL-C? Give the pathway

Less cholesterol reaches the liver → increased hepatic LDL receptor activity → LDL-C decreases.

What is ezetimibe's primary lipid effect?

It decreases LDL-C

What are the major adverse effects of ezetimibe?

Mild GI effects such as diarrhea; possible myalgia or elevated ALT with statins.

Does ezetimibe significantly affect CYP450 enzymes?

No

What is an important ADME feature of ezetimibe?

Undergoes glucuronidation and enterohepatic recycling.

What does PCSK9 normally do?

Promotes degradation of LDL receptors.

What happens when PCSK9 is inhibited?

More LDL receptors are recycled and available to remove LDL-C from blood.

Which PCSK9 inhibitors are monoclonal antibodies?

Evolocumab and alirocumab.

What is the MOA of evolocumab and alirocumab?

Bind circulating PCSK9 and prevent LDL receptor degradation.

What is inclisiran?

A small interfering RNA (siRNA) medication that decreases hepatic PCSK9 production.

How is inclisiran different from PCSK9 monoclonal antibodies?

Inclisiran decreases PCSK9 production; monoclonal antibodies bind existing PCSK9.

What is the primary lipid effect of PCSK9-targeting therapy?

Large decrease in LDL-C.

How are PCSK9 monoclonal antibodies and inclisiran administered?

Subcutaneous injection.

What is a common adverse effect of injectable PCSK9-targeting therapy?

Injection-site reactions.

Why aren't monoclonal antibodies administered orally?

They are large proteins that would be degraded in the GI tract.

Name the three bile acid sequestrants.

Cholestyramine, colestipol, colesevelam.

What is the MOA of bile acid sequestrants?

To bind bile acids in the intestine and prevent their reabsorption.

How does binding bile acids lower LDL-C? Give the pathway

The liver uses more cholesterol to produce bile acids → increases LDL receptor activity → lowers LDL-C.

What can bile acid sequestrants do to triglycerides?

Increase TG levels.

What are common adverse effects of bile acid sequestrants?

Constipation, bloating, and other GI complaints.

Are bile acid sequestrants systemically absorbed?

No. They remain in the GI tract.

Why can bile acid sequestrants cause drug interactions?

They can bind other oral medications and reduce their absorption.

What other substances may have reduced absorption with bile acid sequestrants?

Fat-soluble vitamins A, D, E, and K.

What age group with diabetes commonly has a statin indication regardless of PREVENT risk?

Adults ages 40–75 years.

What statin intensity is generally recommended for adults ages 40–75 with diabetes?

At least moderate-intensity.

When may high-intensity statin therapy be appropriate in diabetes?

When additional ASCVD risk factors or higher cardiovascular risk are present.

Why are some statins recommended in the evening?

Hepatic cholesterol synthesis is greatest overnight.

Which statins are commonly dosed in the evening because of shorter half-lives?

Simvastatin, lovastatin, and fluvastatin immediate-release.

Which two high-intensity statins can generally be taken at any time of day?

Atorvastatin and rosuvastatin.

Why can atorvastatin and rosuvastatin be taken at any time?

Their longer duration of action maintains cholesterol synthesis inhibition.

What is cholesterol point-of-care testing (POCT)?

Rapid lipid testing performed at or near the patient-care location.

What type of sample is commonly used for cholesterol POCT?

Fingerstick capillary blood.

What lipid values may be obtained from cholesterol POCT?

Total cholesterol, HDL-C, triglycerides, and calculated or measured LDL-C.

A patient is 55 years old with diabetes and a 10-year PREVENT risk <10%. What statin intensity and LDL-C goal are recommended?

Moderate-intensity statin; LDL-C <100 mg/dL and ≥30% reduction.

A patient is 55 years old with diabetes and a 10-year PREVENT risk ≥10%. What statin intensity and LDL-C goal are recommended?

High-intensity statin; LDL-C <70 mg/dL and ≥50% reduction.

Why might PREVENT still be used in a patient with diabetes?

To determine whether more intensive lipid-lowering therapy is needed, even though statin therapy is already indicated.

When should a lipid panel be repeated after starting or adjusting lipid-lowering therapy?

4-12 weeks

How often should a lipid panel generally be monitored long-term?

Every 6-12 months

What are we evaluating when monitoring statin efficacy?

LDL-C reduction, achievement of LDL-C goal, and adherence.

Should CK and liver enzymes be routinely monitored in asymptomatic patients taking statins?

No. Obtain them when symptoms suggest muscle or liver injury.

What are phytosterols?

Plant sterols and stanols that reduce intestinal cholesterol absorption.

How much can consuming 2–3 g/day of phytosterols lower LDL-C?

Approximately 5–15%.

Does consuming more than 3 g/day of phytosterols provide additional LDL-C benefit?

No

Are phytosterol supplements routinely recommended for ASCVD prevention? Why?

No, long term ASCVD benefit is uncertain