Non-Statin Cholesterol-Lowering Medications

Updated: Feb. 10, 2021

Other drugs that can be used alone or in conjunction with statins

With statins being hailed as the “drug of the century,” some experts have suspected that, within a few years, half of all Americans will be taking some form of this medication. Although statins are the most popular cholesterol-lowering drugs, there are other options. Many of these are used alone or in conjunction with statins.

If medication combined with lifestyle changes doesn’t enable you to reach your LDL goal within three months, your doctor may consider starting you on a second drug to boost results. Combination therapy can help reverse or slow the advance of atherosclerosis and further decrease your risk of a heart attack or death. Also, since both drugs may be prescribed in lower doses than if you were taking either alone, your risk of side effects may decrease.

Aspirin acts like WD-40 on blood platelets, making them less likely to stick to plaque in blood vessels.
Aspirin acts like WD-40 on blood platelets, making them less likely to stick to plaque in blood vessels.

Become familiar with non-statin drugs, their uses, and the possible side effects. But, as always, consult your doctor before starting any cholesterol-lowering medication.

Cholesterol Absorption Inhibitors
Two organs primarily control cholesterol levels in your blood: the liver, which produces cholesterol and bile acids (used to digest fats), and the intestine, which absorbs cholesterol both from food and from the bile. While statins primarily lower cholesterol by preventing its production in the liver, a new class of drug called cholesterol absorption inhibitors lowers cholesterol by preventing it from being absorbed in the intestine. The first approved drug in this class, Zetia (ezetimibe), hit American markets in 2002.

By itself, Zetia reduced cholesterol about 18 percent in studies. When the drug was paired with statin drugs, cholesterol levels dropped 25 percent more than with statins alone. That’s important, since on average only 60 percent of people who take statins get their cholesterol levels as low as they should. In one study just 19 percent of people taking statins alone reached their cholesterol goal; adding Zetia increased that figure to 72 percent. “Taking 10 milligrams of Zetia with a statin is equivalent to tripling the dose of statins,” says Antonio Gotto, Jr., M.D., dean at Weill Cornell Medical College in New York City. Zetia also has fewer side effects than statins. For instance, it doesn’t appear to cause any muscle problems. The treatment doesn’t come cheaply, however; the wholesale cost for a 30-day supply is $57.90. That’s on top of the cost of the statin. Merck & Co., the maker of the statin Zocor, is testing a pill that combines the two.

Side effects: The most common side effects include back, stomach, and joint pain.

Warnings: Not recommended for use in conjunction with fibrates.

Recommended dose: Zetia is administered as a once-daily tablet in a single 10-milligram strength and is taken with or without food.

Niacin (nicotinic acid) is one of the oldest cholesterol-lowering drugs. A member of the B vitamin family, it’s found in fruits, vegetables, meats, and grains, as well as in most multivitamins. At doses up to 35 milligrams per day, niacin is considered a supplement, but if you’re taking it at doses high enough to lower your cholesterol — more than 100 times the recommended daily intake of 16 milligrams for men and 14 milligrams for women — you need to be taking it under the supervision of your doctor (even though it’s sold over the counter).

Niacin works by reducing the production and release of LDL from the liver, lowering LDL 15 to 20 percent. It also reduces the release of free fatty acids stored in fat cells, which eventually become triglycerides. Thus, it’s an excellent drug for lowering triglycerides, resulting in decreases of 20 to 50 percent. It also raises HDL between 15 and 35 percent. In fact, the branded timed-release form, Niaspan, is one of only two drugs approved to increase HDL. (In case you’re wondering, the other is the fibrate gemfibrozil, brand name Lopid.)

Sound too good to be true? Well, there is a drawback to niacin that turns some people off: It can cause flushing and redness — an intense blush. This occurs because niacin relaxes blood vessels, enabling more blood flow. The blushing usually disappears within an hour or so after taking the drug. And taking aspirin beforehand can reduce this effect, as can gradually building up to the dose you need.

There are two types of nicotinic acid: immediate release and timed release. The timed-release version reduces the flushing, but be doubly sure you don’t take this form without your doctor’s supervision. If you take too much, the drug could cause liver damage and raise blood glucose levels dangerously high. It can also raise blood glucose and hemoglobin AIC levels in people with diabetes. That’s why most experts recommend starting with the immediate-release form. Also, make sure you’re taking nicotinic acid; another form of niacin called nicotinamide doesn’t lower cholesterol levels.

Side effects: In addition to flushing, other possible side effects of niacin include:

  • Liver enzyme abnormalities. About 5 percent of people who take more than 3 grams of nicotinic acid per day may learn they have elevated liver enzymes, an indication that their liver is under stress. If the elevation continues and your enzymes are more than three times normal levels, your doctor may want you to stop taking the drug.
  • Blood glucose control. In about 10 percent of people — particularly those with diabetes, insulin resistance, or metabolic syndrome — nicotinic acid may make it more difficult to control blood sugar levels.
  • Gout. About 5 to 10 percent of those people taking nicotinic acid find their production of uric acid increases. This can result in gout, a condition involving painful and inflamed joints.
  • Gastrointestinal symptoms. Infrequently a variety of gastrointestinal symptoms, including nausea, indigestion, gas, vomiting, diarrhea, and ulcers, may also occur.
  • Muscle toxicity. This is rare but may occur if you’re combining nicotinic acid with other drugs, such as statins or fibrates.

Warnings: Don’t take niacin if you have diabetes, liver disease, an active peptic ulcer, arterial bleeding, or unexplained liver enzyme elevations. And be careful if you’re also taking blood pressure medication. Niacin can increase the effect of some blood pressure drugs, so your doctor should closely monitor your blood pressure when you first start taking niacin.

Recommended dose: 1 to 3 grams daily, taken under a doctor’s supervision.

Fibric acid derivatives, or fibrates, affect the actions of key enzymes in the liver, enabling the liver to absorb more fatty acids, thus reducing production of triglycerides. These drugs also work well at increasing production of HDL. Although they can also lower LDL levels, they’re not considered first-line treatments for high LDL or total cholesterol. Overall, they tend to lower LDL levels between 10 and 15 percent, increase HDL levels between 5 and 20 percent, and lower triglycerides between 20 and 50 percent. Fibrates are often prescribed in conjunction with other cholesterol-lowering drugs, but they shouldn’t be taken with statins. They may be particularly helpful for people with insulin resistance syndrome, in which HDL tends to be low, LDL normal, and triglycerides high. Brands include Atromid-S (clofibrate), Lopid (gemfibrozil), and Tricor (fenofibrate).

Side effects: Fibrates have few side effects and most people can take them with no problem. The most common problems are gastrointestinal complaints, such as nausea and gas. The drug may also increase your likelihood of developing gallstones.

Warnings: Combining fibrates with statins could result in muscle damage. Fibrates are also not recommended if you have liver, kidney, or gallbladder disease.

Recommended dose: Fibrates are usually given in two daily doses totaling 1,200 milligrams, taken 30 minutes before morning and evening meals.

Bile Acid Sequestrants
This class of drug, in use for more than 40 years with no major problems, acts like super glue, binding with bile acids in the intestines so that the acids are removed with the stool. Bile acids (which help your body digest fatty foods) are made from cholesterol in the liver. Ordinarily, as they pass through the intestines they are reabsorbed into the bloodstream and carried back to the liver. This “recycles” the cholesterol component as well. But bile acid sequestrants interrupt this pathway, causing the bile acids to exit the body. This causes a loss of cholesterol as well. In response, the liver removes more LDL from the bloodstream. And — voilà — your blood cholesterol levels drop.

The most common drugs include cholestyramine, sold under the brand names Questran, Prevalite, and LoCholest, and colestipol (Colestid). These drugs generally lower LDL about 15 to 30 percent with relatively low doses while increasing HDL slightly (up to 5 percent). They may be prescribed with a statin if you already have heart disease. Together the two drugs can lower LDL more than 40 percent.

Side effects: These drugs may cause bloating, heartburn, constipation, and abdominal pain, and may increase triglycerides, particularly if levels are already high.

Warnings: Bile acid sequestrants may delay or reduce your ability to absorb oral medications and vitamins, so you shouldn’t take them along with other medications or supplements.

Recommended dose: Bile acid sequestrants generally come as tablets or as a powdered resin that you mix with liquids or foods. A typical dose is about 10 grams per day.

First the proviso: Aspirin won’t lower your cholesterol. But its effects on blood clotting and inflammation are so significant that anyone with known heart disease, diabetes, or two or more risk factors for heart disease (and no problems taking aspirin) should talk to their doctor about taking a daily baby aspirin. Aspirin acts like WD-40 on blood platelets, making them less likely to stick to plaque in blood vessels. It also reduces the inflammation that is a hallmark of heart disease and a part of the process that leads to the buildup of plaque.

Numerous studies have found that aspirin reduced the risk of another heart attack, stroke, or premature death in people with heart disease, and it also reduced the risk of heart attacks in healthy people. One analysis of four large studies conducted on people with no history of heart disease found a daily aspirin reduced the risk of a nonfatal heart attack 32 percent.

Side effects: Aspirin’s very strength is also its greatest weakness. Because it acts on the overall system that affects bleeding, aspirin increases the risk of gastrointestinal bleeding, either from an ulcer or gastritis (inflammation of the stomach lining), and the risk of a rare but dangerous form of stroke called hemorrhagic stroke, caused not by a blood clot but by bleeding in the brain. To learn whether the benefits of aspirin therapy outweigh the risk for you personally, take the simple test at You will need to know your blood pressure and cholesterol readings.

Warnings: If you’re taking blood-thinning medication such as Coumadin (warfarin), talk to your doctor before taking aspirin regularly. The combined effect can pose a serious hazard. And be aware that aspirin can boost the blood-thinning effects of certain supplements, such as vitamin E, ginkgo biloba, St. John’s wort, and others. (Fish oil also thins the blood, but the heart benefits of taking both fish oil and aspirin probably outweigh the risks.) Be sure to let your doctor know about any supplements you take when you discuss the pros and cons of aspirin therapy with him. Finally, don’t take aspirin if you’ve ever had any problems with the drug,
including stomach pain or allergies.

Recommended dose: One baby aspirin (81 milligrams) daily.

Reader's Digest
Originally Published in Reader's Digest