A Guide to Cholesterol Medication

A Guide to Cholesterol Medication

Cholesterol medications help lower total cholesterol within the body.  Cholesterol is a natural waxy, fat-like substance that is carried through the bloodstream to different organs and tissues.  Although cholesterol is essential for human health, too much “bad” (low-density lipoproteins or LDL) cholesterol or not enough “good” (high-density lipoproteins or HDL) cholesterol can put you at risk for coronary heart disease, heart attack, or stroke.  This is because LDL can build up in the arteries, causing the artery to limit blood flow.  HDL is important because it clears the build-up of such damaging cholesterol.

About 25% of our total cholesterol comes from the food we eat.  Cholesterol is only found in animal products, such as milk, eggs, and meat.  Fruits, vegetables, grains, and all other plant foods do not have any cholesterol at all.  The rest of our total cholesterol is produced by the body.

High levels of triglycerides, a type of fat (lipid) in your blood produced from unused calories, can also increase your risk of heart disease.

Cholesterol-lowering medications work by blocking the substance your body needs to make cholesterol.  Medications may also reduce triglycerides and help your body reabsorb cholesterol that has built up as plaque on your artery walls.  This prevents further blockage in your blood vessels and potential heart attacks.

An estimated 1 in 7 Americans has high blood cholesterol, resulting in 800,000 deaths each year.  Approximately 30 million Americans take cholesterol-lowering medication, making them the most prescribed medications in the U.S.  Although cholesterol-lowering medications can help a lot of people, as with any medication, there are risks to taking these drugs.  You should try to find other ways of lowering your cholesterol that might be a better option for you and your health.  If those other strategies are successful, you might not need these drugs or might be able to take a lower dose of these drugs.

The key to lower cholesterol and reduced risk of heart disease is through lifestyle changes. Lifestyle changes include exercising at least 30 minutes a day on most days of the week; eating a healthy diet low in fat, cholesterol, and salt; managing stress; and quitting smoking.  Even if you decide to take cholesterol-lowering medication or have been taking it for a while, these lifestyle behaviors are important for managing cholesterol.

You should also know that once you start taking cholesterol-lowering medication, you will usually need to continue taking the drug indefinitely.  Even if your cholesterol drops to the desired level while on medication, many people find that once they stop taking cholesterol-lowering drugs, their levels go back up unless they have changed their eating, exercising, smoking, or other habits.  The long-term effects of many of these drugs have not been adequately studied, so the risks and benefits over several decades of use are generally unknown.

What do your cholesterol levels tell you?

If you have high cholesterol, your doctor may recommend you take medication.  This chart explains what your cholesterol levels tell you:

If your Total Cholesterol level is:

This is considered:

Less than 200 mg/dL

Desirable

200-239 mg/dL

Borderline

240 mg/dL and above

High

If your LDL Cholesterol level is:

This is considered:

Less than 100 mg/dL

Optimal

100-129 mg/dL

Near optimal/above optimal

130-159 mg/dL

Borderline high

160-189 mg/dL

High

190 mg/dL and above

Very high

If your HDL Cholesterol level is:

This is considered:

Less than 40 mg/dL

Low, increases risk

41 – 59 mg/dL

OK, but less than optimal

60 mg/dL and above

Good, helps lower risk

The numbers alone won’t tell you or your doctor the entire story, however.  If the only risk factor you have is high cholesterol, you may not need medication.  Often high cholesterol can be lowered by exercise and a healthy diet.  High cholesterol is only one of a number of risk factors for heart attack and stroke.  Other risk factors include:

· Family history of high cholesterol or cardiovascular disease

· Inactive (sedentary) lifestyle

· High blood pressure

· Age—older than 55 if you’re a man, or older than 65 if you’re a woman

· Poor general health

· Having diabetes

· Overweight or obesity

· Smoking

· Narrowing of the arteries in your neck, arms, or legs (peripheral artery disease)

Overview of Cholesterol-Lowering Medications

Once your cholesterol level is considered along with other risk factors, you and your doctor may decide that taking medication is a good option.  There are many cholesterol-lowering medications on the market today, but which of these drugs is right for you?  Here is an overview of benefits, concerns, and possible side effects for common types, or classes, of cholesterol medication:[1]

Drug class

Drug Function

Drug names

Benefits

Possible side effects

Statins

Inhibits the enzyme the body needs to make cholesterol

Altoprev (lovastatin)

Crestor (rosuvastatin)

Lescol (fluvastatin)

Lipitor (atorvastatin)

Livalo (pitavastatin)*

Mevacor (lovastatin)

Pravachol (pravastatin)

Zocor (simvastatin)

Decrease LDL and triglycerides; slightly increase HDL

Constipation, nausea, diarrhea, stomach pain, cramps, muscle soreness and possible damage, memory loss, forgetfulness, confusion, pain and weakness, increased risk of diabetes; possible interaction with grapefruit juice

Bile acid binding resins

Prevents bile from being reabsorbed into the circulatory system

Colestid (colestipol)

Prevalite (cholestyramine)

Questran (cholestyramine)

Welchol (colesevelam)

Decrease LDL

Constipation, bloating, nausea, gas; may increase triglycerides

Cholesterol absorption inhibitors

Blocks the amount of cholesterol that is absorbed by the small intestine

Zetia (ezetimibe)

Decrease LDL; slightly decrease triglycerides; slightly increase HDL

Stomach pain, fatigue, muscle soreness

Combination cholesterol absorption inhibitor and statin

Inhibits production of cholesterol and blocks absorption of cholesterol by the small intestine

Vytorin (ezetimibe and simvastatin)

Decreases LDL and triglycerides, increases HDL

Stomach pain, fatigue, gas, constipation, abdominal pain, cramps, muscle soreness, pain and weakness; possible interaction with grapefruit juice

Fibrates

Reduces production of triglycerides

Bezalip (bezabifrate)

Lofibra (fenofibrate)

Lopid (gemfibrozil)

TriCor (fenofibrate)

Decrease triglycerides; increase HDL

Nausea, stomach pain, gallstones

Niacin

Lowers the liver’s ability to produce LDL

Niaspan

Decreases LDL and triglycerides; increases HDL

Facial and neck flushing, nausea, vomiting, diarrhea, gout, high blood sugar, peptic ulcers

Combination statin and niacin

Inhibits production of cholesterol

Advicor (niacin and lovastatin)

Decreases LDL and triglycerides; increases HDL

Facial and neck flushing, dizziness, heart palpitations, shortness of breath, sweating, chills; possible interaction with grapefruit juice

Omega-3 fatty acids

Inhibits production of triglycerides in the liver

Lovaza (prescription omega-3 fatty acid supplement)

Decreases triglycerides

Belching, fishy taste, increased infection risk

*Livalo (pitavastatin) became available on the market in mid-2010. Livalo is new and does not have the long track record of some of the other statins, so you may want to avoid this drug until more is known about it.

What Does Research Say About Cholesterol-Lowering Medications?

There are so many medications to choose from, but knowing which one is best for your body and health can be confusing.  You will decide together with your doctor, but doctors are often not aware of all the latest research.  Below is a summary of some of the most important studies on cholesterol medication, with conclusions that may help steer you away from drugs with greater risks or drugs that may lower your cholesterol without reducing your chances of heart attack or stroke!

Vytorin: Zocor + Zetia

A study published in the New England Journal of Medicine in 2008 found that Vytorin was less effective at reducing risk of heart disease compared to taking Zocor alone.[2] Researchers found that while Vytorin was more effective at lowering cholesterol, it was not better at reducing plaque build up in the arteries compared to Zocor alone.  In fact, the arterial wall was thicker for patients taking Vytorin.  Two patients taking the combination pill died, compared to one taking Zocor, and three of the patients taking the combination pill had non-fatal heart attacks, compared to two taking Zocor.  These differences were not statistically significant, meaning they could happen by chance, but they suggest that Zocor alone is a better choice than Vytorin.  The final results of the two-year clinical trial indicated that patients taking Vytorin were at the same risk of heart disease as the patients who took Zocor alone.  Why take 2 drugs at once if the second one is not helpful and may be harmful? Conclusion: Vytorin (Zocor + Zetia) is not more effective than Zocor alone.

After the above study was published, doctors were advised that Zetia (one of the drugs in Vytorin) should only be used if all other medications have failed.  The listed side effects for Zetia include: stomach pain, tiredness, allergic reactions, and joint pain.  Rarely, patients also experience severe muscle problems with symptoms of muscle pain, tenderness, or weakness caused by muscle breakdown.[3]

A study published in the New England Journal of Medicine in November 2009 reported that patients taking Vytorin (a combination of Zocor + Zetia) were more likely to have heart attacks or die from heart disease than patients taking a combination of Zocor + Niaspan.  Niaspan is an extended release form of niacin (a type of vitamin B).[4] The patients taking Vytorin also had more plaque build up in their arteries compared to patients taking Zocor + Niaspan.  This is further evidence that Vytorin is not helpful and may be harmful compared to other medications.  Conclusion: Vytorin (Zocor + Zetia) may have more serious side effects than Zocor + Niaspan.

National Center for Health Research believes that the evidence indicates that patients should choose other cholesterol lowering drugs rather than Vytorin.

Zocor

In June 2011, the Food & Drug Administration (FDA) recommended limiting the use of high-dose (80 mg) simvastatin (Zocor, Vytorin, and generic) due to risk of muscle injury.[5] The recommendation came after a review of clinical trial data and data from the agency’s Adverse Event Reporting System, one of the FDA’s most important tools for tracking the safety of drugs that are already on the market.  The reviewers found a clear link between high-dose simvastatin and muscle pain.  Rare but potentially deadly muscle damage was also linked to high-dose simvastatin, particularly for older women and those who took simvastatin in addition to blood-pressure drugs, especially diltazem (Cardizem and generic).

People starting simvastatin treatment for high cholesterol, as well as those who’ve taken simvastatin for less than one year, should begin with or switch to a lower dose.  For those who’ve taken the 80 mg dose for 12 months or longer without any muscle problems, the FDA said continuation of the high dose is likely not a problem.

However, since the difference in cholesterol lowering between a dose of 80 mg and a dose of 40 mg is only about 6%, according to the FDA, medical consultants say even individuals who have taken the 80 mg dose for 12 months or more should consider switching to a lower dose.

The FDA also warned about taking simvastatin with certain other drugs.  Notably, it issued new limits for people taking simvastatin along with several heart medications, including:

· No more than 20 mg of simvastatin when taken with amlodipine (Norvasc and generic)

· No more than 10 mg of simvastatin when taken with diltiazem (Cardizem and generic or verapamil (Verelan and generic)

· No more than 20 mg of simvastatin when taken with amiodarone (Cardarone)

· No more than 20 mg of simvastatin when taken with ranolazine (Ranexa)

The agency also added several drugs to the current list of medications that should never be used with simvastatin.  The full list includes:

· Clarithromycin

· Cyclosporine

· Danazol

· Erythromycin

· Gemfibrozil

· HIV protease inhibitors

· Itraconazole

· Ketoconazole

· Posaconazole

· Nefazodone

· Telithromycin

In light of these findings, NRC reiterates its recommendation that patients find safer alternatives to Vytorin, and avoid high-dose simvastatin drugs.

Altoprev and Mevacor

The drugs Altoprev and Mevacor contain a type of statin called lovastatin.  Recent evidence has shown that lovastatin is very similar to simvastatin.  Accordingly, the FDA issued warnings in February 2012 that lovastatin should not be taken in with a number of other drugs, such as the common antibiotic, erythromycin, and HIV protease inhibitors.[6]

The full list of medications that should never be used with lovastatin includes:

· Itraconazole

· Ketoconazole

· Posaconazole

· Erythromycin

· Clarithromycin

· Telithromycin

· HIV protease inhibitors

· Boceprevir

· Telaprevir

· Nefazodone

Niacin

A study by the National Heart, Lung, and Blood Institute of the National Institutes of Health found that adding high dose, extended-release niacin to statin treatment in people with heart and vascular disease did not reduce the risk of cardiovascular events, including heart attacks and stroke.[7] Participants who took Zocor and extended-release niacin of up to 2,000 mg per day had increased “good” (HDL) cholesterol and lowered triglyceride levels compared to patients who took Zocor alone.  However, the combination treatment did not reduce fatal or non-fatal heart attacks, strokes, hospitalizations for acute coronary syndrome, or revascularization procedures to improve blood flow in the arteries of the heart and brain. Conclusion: Niacin + statin treatment might increase good (HDL) cholesterol and lower triglycerides compared to statin alone, but it does not reduce overall risk of serious health outcomes like heart attack or stroke.

Risk of Muscle Injury

Muscle injury due to statin use is a leading cause of statin intolerance and the most common reason people stop taking statin medication.  Studies estimate that 10 – 15% of statin users develop muscle side effects ranging from mild discomfort to more severe muscle symptoms.  Although severe muscle symptoms (myotoxicity) are very rare, most recent studies suggest that muscle pain (myalgias) and minor muscle damage may occur in a substantial number of patients treated with statins.[8]

A growing body of research on statin use suggests that the risk of muscle problems depends mostly on the dose.  For example, four large trials including 27,548 patients compared high-dose statin use (atorvastatin or simvastatin at 80 mg/day) to moderate-dose statin use (pravastatin at 40 mg/day, simvastatin at 20 mg/day, or atorvasatin at 10 mg/day).  High-dose use was linked to a reduced risk of cardiovascular events, such as heart attack, stroke, or death.  But, patients taking a high dose statin were 10 times more likely to have muscle problems than patients taking a moderate dose statin.[9] Conclusion: Patients on high-dose statin therapy (especially simvastatin) are at an increased risk of muscle-related side effects.

Risk of Diabetes

For people with a history of coronary heart disease, heart attack or acute coronary syndrome, an analysis of five clinical trial studies found a link between the onset of diabetes and high-dose statin intake, compared to moderate-dose intake.  The 2011 analysis defined high-dose statin therapy as 80 mg of statin medication, while moderate-dose therapy was defined as either 40 mg, 20 mg or 10 mg, depending on the study.  Across all five studies, patients who have suffered acute coronary syndrome (ACS) and patients who have stable coronary heart disease were more likely to develop diabetes if they were taking higher doses of statins.  Acute coronary syndrome is a medical term that includes any symptoms of an insufficient blood supply to the heart muscle. Conclusion: High-dose statins can increase the risk of diabetes.

Statin Use among Children

Several statins are approved by the FDA for use in children.  Some are approved for children over 8 years of age and others for children at least 10 years of age.  Approved statins include: atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Altoprev, Mevacor and generic), pravastatin (Pravachol and generic), rosuvastatin (Crestor), and simvastatin (Zocor and generic).[10]

Statins are usually used to treat children with genetic conditions that cause hyperlipidemia, which is an excess of lipids like cholesterol and triglycerides in the blood.  Short term studies in children show some improvement in measures like LDL cholesterol, blood flow, and thickness of the artery walls.  However, statin research has not studied children for more than 2 years, so we don’t know the long-term risks of statins for children, or if treatment in childhood actually improves health over a longer period of time or into adulthood.7,[11] We also don’t know which of the statins work better in children.7

Genetic conditions in children can increase the risk of vascular disease in adulthood, but so can obesity and diabetes.  Around 17% (or 12.5 million) of Americans aged 2-19 years are obese.  This is almost three times higher than the rate of obesity in 1980.[12] Before a statin is prescribed, parents should make dietary and lifestyle changes for the whole family to improve health and vascular functioning.  More exercise and a “heart-healthy” diet can improve cholesterol, blood pressure, weight and other risk factors.7 A “heart-healthy” diet is high in whole grains, fish, fruit, and vegetables and is low in salt and sugar-added products.

Many doctors question whether children should take statins, especially when it is used before trying to make positive diet and exercise changes.  Doctors point out that a healthy weight, healthy diet, and physical activity could be as effective as statins, in addition to reducing the risk of other diseases and eliminating the side effects of the drugs.[13] We don’t know if or how statin use by children might influence development of the brain or other organ systems.  Long-term drug therapy beginning at this young age could affect the central nervous system, immune function, hormones, metabolism or have other unexpected effects.10 For those reasons, use by children should be avoided except under rare circumstances.

Conclusion

If you need to reduce your cholesterol, make sure you think about the risks and benefits of taking cholesterol medication.  It is a good idea to try to improve your cholesterol through a “heart-healthy” diet and regular physical activity.  If these efforts do not work and you need to start taking a prescription cholesterol drug, make sure you find one that is proven safer, more effective, and right for you.

If you are already taking a prescription cholesterol drug and are experiencing possible side-effects, talk with your doctor about your options.  There may be another drug that could work for you.  Also, be aware of the latest findings and conclusions about cholesterol medication, including those mentioned in this article!


[1] Mayo Clinic, High Cholesterol

[2] Kastelein J, Akdim F, Stroes ESG, et al. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia. The New England Journal of Medicine. 2008;358:1431-1443.

[3] FDA Patient Information Sheet: Ezetimibe (marketed as Zetia). July 2006. Retrieved at http://www.fda.gov/Cder/drug/InfoSheets/patient/ezetimibePIS.htm

[4] Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or Ezetimibe and carotid intima-media thickness. The New England Journal of Medicine. 2009;361:2113-2122.

[5] FDA: Limit Use of 80 mg Simvastatin. Consumer Health Information. June 2011. Retrieved at http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/UCM257911.pdf

[6] FDA. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering drugs. February 2012. http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm

[7] National Heart, Lung, and Blood Institute. NIH stops clinical trial on combination cholesterol treatment. 26 May 2011. Retrieved at http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=2792

[8] Mammen AL, Amato AA, Statin myopathy: a review of recent progress. Current Opinion in Rheumatology. 2010;22:644-650.

[9] Silva M, Matthews ML, Jarvis C, et al. Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy. Clinical Therapeutics. 2007;29:253-260.

[10] O’Gorman CSM, O’Neill MB & Conwell LS (2011).  Considering statins for cholesterol-reduction in children if lifestyle and diet changes do not improve their health: a review of the risks and benefits.  Vascular Health and Risk Management, 7:1-14.

[11] Vuorio A, Kuoppala J, Kovanen PT, Humphries SE, Strandberg T, Tonstad S, & Gylling H (2011).  Statins for children with familial hypersholesterolemia.  Cochrane Database of Systematic Reviews, Issue 7.

[12] Centers for Disease Control and Prevention, Overweight and Obesity.  April 2011. Retrieved at: http://www.cdc.gov/obesity/childhood/data.html

[13] Ferranti S & Ludwig D (2008).  Storm over Statins—The Controversy Surrounding Pharmacologic Treatment of Children.  N Engl J Med, 359;13:1308-12.