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Beyond statins: Assessing the alternatives

Some people can’t tolerate statins, and others need additional medications to achieve healthy cholesterol levels.

In the realm of cardiovascular medicines, statins reign supreme. These drugs lower the risk of heart attack in people who have—or may develop—heart disease.

“The benefits of statins are directly related to how much they lower LDL cholesterol,” says Dr. Christopher Cannon, professor of medicine at Harvard Medical School and a cardiologist at Brigham and Women’s Hospital. For every 40-point reduction in LDL, the risk of a heart attack drops by about 20%. Statins also help fight inflammation, stabilize plaque inside the arteries, and prevent blood clots, all of which likely contribute to their heart-protecting effects.

Statin substitutes?

But about 10% of people who try statins experience bothersome side effects (most commonly, muscle aches) that prevent them from taking these useful drugs. Still others take high-dose statins, but their harmful LDL cholesterol levels remain elevated.

While LDL is considered the most critical lipid (fat) in the blood, levels of other lipids—namely, HDL and triglycerides—may affect heart disease progression. Statin alternatives don’t improve lipid levels to the same degree, nor do they have statins’ proven heart attack–prevention powers. But doctors recommend them in specific situations. Here’s the latest on the benefits, risks, and appropriate use of non-statin drugs.


Ezetimibe (Zetia) lowers LDL by about 20%. It’s well tolerated and has a good safety record but hasn’t been shown to prevent heart disease or heart attacks. Most experts consider it a safe way to reduce LDL in people who can’t take a statin.

Vytorin, a drug that combines the statin simvastatin (Zocor) with ezetimibe, lowers LDL more than either drug alone. Whether that translates to fewer heart problems isn’t yet known. Results from a large study comparing Vytorin with simvastatin alone, called IMPROVE-IT, are slated for release this fall and should help clarify the drug’s role. In the meantime, if you’re taking Zetia with a low- or moderate-intensity statin, such as simvastatin, ask your doctor if you should switch to a high-dose statin. Examples include 80 mg of atorvastatin (Lipitor) and 20 or 40 mg of rosuvastatin (Crestor). The higher doses have been shown to reduce heart attack and stroke more than the moderate doses, Dr. Cannon says.

Non-statin drugs to improve lipid levels

Cholesterol absorption inhibitor

  • ezetimibe (Zetia)

Bile acid binders

  • cholestyramine
    (Locholest, Prevalite, Questran)

  • colesevelam (Welchol)

  • colestipol (Colestid)


  • fenofibrate (TriCor)

  • gemfibrozil (Lopid)


  • vitamin B3, nicotinic acid, generic nonprescription niacin

  • niacin (Niaspan, Niacor, Slo-Niacin)

Bile acid binders

These drugs lower LDL by 15% to 30% but may raise triglycerides in people with elevated levels. Side effects include bloating, heartburn, and constipation. Because they also lower blood sugar slightly, bile acid binders may be appropriate add-on drugs for people with type 2 diabetes who take statins but still have high LDL levels.

Image: Thinkstock

Before statins came on the scene, people took a range of other lipid-lowering medications. These drugs may still be useful in certain situations.


Fibrates are most often used to lower high triglyceride levels, although they also lower LDL slightly and raise HDL a bit. But people taking high-dose statins should only take a fibrate with caution, as this combination has caused rare cases of a potentially deadly breakdown of muscle tissue called rhabdomyolysis.


Niacin, also known as vitamin B3, has long been used to raise HDL cholesterol. But a number of recent studies have shown that in people already on statins, boosting HDL by taking niacin doesn’t prevent cardiovascular events. And even the best-tolerated form, sustained-release niacin, may cause itching, facial flushing, and headaches, as well as more serious side effects such as gout and liver problems. Most people should not take niacin, says Dr. Cannon. Exceptions might include people with a severe case of a rare condition called familial hypercholesterolemia whose LDL cholesterol is not lowered enough by statins alone, and people with extremely low HDL levels (in the 20s or lower). 

Posted by: Dr.Health

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