Prophylaxis of Atherosclerotic Cardiovascular Disease: Drugs That Help Normalize Cholesterol and Triglyceride Levels

Question 1

HMG-CoA Reductase Inhibitors (Statins)

Answer 1

• Most effective drugs for lowering LDL • Reduction of LDL cholesterol
• Elevation of HDL cholesterol
• Reduction of triglyceride levels
• Nonlipid beneficial cardiovascular actions
• Promote plaque stability
• Reduce the risk for cardiovascular (CV) events • Increased bone formation
• Mechanism of cholesterol reduction • Administer at night
• Clinical trials
• Therapeutic uses
• Hypercholesterolemia
• Primary and secondary prevention of CV events • Post-MI therapy
• Diabetes
• Potential uses
• Beneficial actions
• Reduction of LDL cholesterol
• Elevation of HDL cholesterol
• Reduction of triglyceride levels
• Nonlipid beneficial cardiovascular actions • Increased bone formation
• Adverse effects
• Common
• Headache
• Rash
• GIdisturbances • Rare
• Myopathy/rhabdomyolysis • Hepatotoxicity
• New-onsetdiabetes
• Cataracts

• Drug interactions
• Most other lipid-lowering drugs (except bile acid
sequestrants)
• Drugs that inhibit CYP3A4 • Use in pregnancy
• Dosing: Once daily in the evening
• Endogenous cholesterol synthesis increases
during the night
• Statins have greatest impact when given in the evening

Question 2

Nicotinic Acid (Niacin)

Answer 2

• Reduces LDL and TG levels
• Increases HDL levels more effectively than any
other drug
• Effect on plasma lipoproteins
• Lowers TG levels
• Raises HDL cholesterol

• Adverse effects
• Skin (flushing, itching)
• Intenseflushinginitially;canpretreatwithaspirin
• Decreasedwithsustained-release(SR)versionof niacin
• Gastrointestinal • Hepatotoxicity • Hyperglycemia • Gouty arthritis
• Can raise blood levels of uric acid

Question 3

Cholestyramine
• Colestipol
• Colesevelam
• Newest and better-tolerated drug
• Does not decrease uptake of fat-soluble vitamins (as other bile sequestrants do)
• Does not significantly reduce the absorption of statins, warfarin, digoxin, and most other drugs studied

Answer 3

Bile Acid Sequestrants

• Previously were first-line drugs
• Now primarily used as adjuncts to statins

Question 4

• Colesevelam

Answer 4

• Reduces LDL cholesterol
• Increases VLDL levels in some patients • Mechanism of action
• IncreasesLDLreceptorsonhepatocytes • Preventsreabsorptionofbileacids
• Therapeutic use
• ReducesLDLcholesterol(inconjunctionwith
modified diet and exercise) • Adverse effects
• Constipation

Question 5

Ezetimibe

Answer 5

• Mechanism of action and impact on plasma lipids
• Inhibits cholesterol absorption • Therapeutic use
• Reduces total cholesterol, LDL cholesterol, and apolipoprotein B
• Approved for monotherapy and combined use with statins
• Adverse effects • Myopathy
• Rhabdomyolysis
• Hepatitis
• Pancreatitis
• Thrombocytopenia
• Drug interactions • Statins
• Fibrates
• Bile acid sequestrants • Cyclosporine

Question 6

Gemfibrozil

Answer 6

• Effects on plasma lipoproteins • Decreases plasma TG content
• Lowers VLDL levels
• Can raise HDL cholesterol
• Mechanism
• Appears to interact with a specific receptor subtype
(PPAR alpha)
• Drug interactions
• Displaces warfarin from plasma albumin
• Measure international normalized ratio (INR) frequently

• Therapeutic uses
• Reduces high levels of plasma triglycerides (VLDLs)
• Treatment reserved for patients who have not responded to diet modification
• Less effective than statins in reducing LDL
• Can raise HDL (not approved for this use)
• Adverse effects • Rashes
• Gastrointestinal disturbances • Gallstones
• Myopathy
• Liver injury (hepatotoxic)

Question 7

Monoclonal Antibodies

Answer 7

• Praluent and Repatha
• For high LDL with family hx and CAD
• Adjunct to diet and max tolerated statin
• PCSK9 is protein that binds to LDLRs in liver and it is inhibited
• SQ injection q 2weeks, and half life is 11-20 days
• SE: rash, antibodies