Review of Medications for the Treatment of High Cholesterol

Background

Cholesterol in is made by the liver and also comes from foods like meat and dairy products.  There are two main types of cholesterol: ‘good’ and ‘bad’ cholesterol. High levels of bad cholesterol known as low density lipoprotein (LDL) can lead to heart attack, stroke and heart disease. Good cholesterol or high density lipoprotein (HDL) helps get rid of bad cholesterol by moving it from the arteries to the liver where it is removed from the body. Total cholesterol (TC) is the total amount of cholesterol circulating in blood. It includes LDL, HDL and VLDL (another type of ‘bad’ cholesterol). In general, a higher HDL and lower LDL and total cholesterol are preferred.

Other factors that can increase cholesterol include:

• Drugs such as diuretics, glucocorticoids and amiodarone

• Diseases such as biliary obstruction and nephrotic syndrome

• Conditions that cause a change in metabolism such as hypothyroidism, obesity and pregnancy

Health impact of high cholesterol

71 million Americans have high LDL cholesterol and less than half are getting treatment. It is important to know your cholesterol levels in order to determine your risk of getting heart disease, the leading cause of death in the US.

Optimum cholesterol levels

LDL Cholesterol

Less than 100 (Optimal)

100 to 129 (Near optimal/above optimal)

130 to 159 (Borderline high)

160 to 189 (High)

Greater than 190 (Very high)

Total Cholesterol

Less than 200 (Desirable)

200 to 239 (Borderline high)

Greater than 240 (High)

HDL Cholesterol

Less than 40 (Low)

Greater than 60 (High)

Drugs used for treating high cholesterol 
(Combination drug products have not been included in this review.)

Statins or HMG-CoA inhibitors

Examples of statins:

rosuvastatin (Crestor)

atorvastatin (Lipitor)

simvastatin (Zocor)

lovastatin (Mevacor)

pravastatin (Pravachol)

pitavastatin (Livalo)

fluvastatin (Lescol)

Mechanism of action of statins: Inhibits production of HMG-CoA, an enzyme needed to make cholesterol

Side effects of statins

fatigue

myopathy

stomach pain

constipation

Availability: Prescription

Drug interactions of statins

erythromycin

ketoconazole

danazol

gemfibrozil

cyclosporine

indinavir

amlodipine

diltiazem

niacin

Effect of statins

18 to 55% LDL reduction

5 to 15% HDL increase

7 to 30% TG reduction

Contraindications for statins: active or chronic liver disease

Bile acid sequestrants

Examples of bile acid sequestrants

cholestyramine (Questran)

colesevelam (Welchol)

colestipol (Colestid)

Mechanism of action of bile acid sequestrants: Cause a reduction in cholesterol levels by binding to bile acid. This increases activity of the LDL receptor, resulting in removal of more LDL from the blood.

Side effects of bile acid sequestrants

nausea

vomiting

constipation

stomach discomfort

Availability: Prescription

Drug interactions of bile acid sequestrants:

mycophenolate

It also causes a decrease in absorption of other drugs when taken together

Effect of bile acid sequestrants

15 to 30% LDL reduction

3 to 5% HDL increase

No change or increase in TG

Contraindications of bile acid sequestrants

dysbetalipoproteinemia

TG greater than 400 mg/dL

Fibrates (Fibric acid) 

Examples of fibrates

fenofibrate (Tricor)

gemfibrozil (Lopid)

fenofibric acid (Trilipix)

Mechanism of action: Activates PPAR alpha receptors to reduce triglycerides.

Side effects of fibrates

nausea

stomach pain

dyspepsia

gallstones

myopathy

Availability: Prescription

Drug interactions of fibrates

statins

anticoagulants

Effect of fibrates

5 to 20% LDL reduction (may be higher in patients with high TG)

10 to 20% HDL increase

20 to 50% TG reduction

Contraindications of fibrates: severe renal or hepatic disease

Cholesterol absorption inhibitor    

Examples: ezetimibe (Zetia)

Mechanism of action of Zetia: Inhibits absorption of cholesterol from the small intestine

Side effects of Zetia

diarrhea

muscle pain

Availability: Prescription

Drug interactions of Zetia: cholestyramine

Effect of Zetia

13% LDL reduction

3.5% HDL increase

8% TG reduction

Contraindications

active liver disease

unexplained persistent elevations in hepatic transaminase

Niacin (Nicotinic acid)

Examples of niacin

slo-Niacin

niaspan

Mechanism of action: Inhibits production of LDL from the liver and raises HDL.

Side effects of niacin

flushing

itching

hyperglycemia

hyperuricemia (or gout)

upper gastrointestinal distress

hepatotoxicity

Availability: Prescription and OTC

Drug interactions of niacin: statins

Effect of niacin

5 to 25% LDL reduction

15 to 35% HDL increase

20 to 50% TG reduction

Contraindications of niacin

chronic liver disease

severe gout

Omega-3 fatty acids

Examples:

lovaza

fish oil

Mechanism of action: Inhibits production of TG in the liver

Side effects of omega-3 fatty acids

burping

indigestion

increased risk of bleeding

Availability: Prescription and OTC

Drug interactions of omega-3 fatty acids: anticoagulants

Effects of omega-3 fatty acid: 10% LDL increase

No effect on HDL

25 to 50% TG reduction

Contraindications of omega-3 fatty acids: Known hypersensitivity to omega-3 acids or any product component

Cholesterol reducing effect of various statin doses

High-Intensity Statin Therapy (50% or greater reduction in LDL)

atorvastatin 40 to 80 mg

rosuvastatin 20 to 40 mg

Moderate-Intensity Statin Therapy (30% to less than 50% reduction in LDL)

atorvastatin 10 to 20 mg

rosuvastatin 5 to 10 mg

simvastatin 20 to 40 mg

pravastatin 40 to 80 mg

lovastatin 40 mg

fluvastatin XL 80 mg

fluvastatin 40 mg twice daily 

pitavastatin 2 to 4 mg

Low-Intensity Statin Therapy (less than 30% reduction in LDL)

simvastatin 10 mg

pravastatin 10 to 20 mg

lovastatin 20 mg

fluvastatin 20 to 40 mg

pitavastatin 1 mg

Percent reductions in LDL were determined by data meta-analyses by the Cholesterol Treatment Trialists (CTT) in 2010. This included data from 170,000 subjects in 26 randomized controlled trials. Individual response may vary.

Conclusion

There are many treatment options available for the treatment of high cholesterol. Your doctor may also recommend lifestyle changes such as regular exercise, following a diet low in saturated fat or weight management.

Resources

About Cholesterol. American Heart Association

ATP III Guidelines At-A-Glance: Quick Desk Reference. National Cholesterol Education Program.

Bays, HE et al. Effectiveness and Tolerability of Ezetimibe in Patients with Primary Hypercholesterolemia: Pooled Analysis of Two Phase II Studies."Clinical Therapeutics 23.8 (2001): 1209-230.

CDC. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol. United States, 1999–2002 and 2005–2008. MMWR. 2011;60(4):109–14.

Cholesterol Treatment Trialists Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomized trials. Lancet 2010;376:1670–1681.

Cholestyramine. In: Clinical Pharmacology. Tampa (FL): Elsevier/Gold Standard. (Updated Oct 12, 2009). Accessed July 30, 2014.

DiPiro, Joseph T. et al. Pharmacotherapy: A Pathophysiologic Approach 8^th ed:365-84.

Ezetimibe. In Clinical Pharmacology. Tampa (FL): Elsevier/Gold Standard. (Updated Nov 19, 2009). Accessed July 30, 2014.

Fish Oil, Omega-3 Fatty Acids (Dietary Supplements). In: Clinical Pharmacology. Tampa (FL): Elsevier/Gold Standard. 

Hoyert  DL, et al. Deaths: Preliminary Data for 2011. National Vital Statistics Reports. 2012;61(6):16-17.

Stone, NJ, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Journal of the American College of Cardiology (2013).

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). National Cholesterol Education Program.  2002. NIH Publication No. 02-5215.