Cholesterol Drugs

What types of cholesterol-lowering medications are available?

There are five major categories of prescription drugs available for improving your cholesterol levels. Cholesterol is a lipid, or fat, found in the blood. LDL cholesterol, known as “bad” cholesterol, increases your risk for heart disease. You want a low level of LDL cholesterol (less than 100 mg/dL is best). HDL cholesterol is considered “good” cholesterol. You want a high level of HDL cholesterol (more than 50 mg/dL is best). Total cholesterol is the sum of all the cholesterol in your blood, including both LDL and HDL cholesterol (less than 200 mg/dL is best). Triglycerides are another type of lipid that can raise your risk of heart disease (less than 150 mg/dL is best). Your healthcare provider may prescribe a medication from one or more of the five drug categories depending on your lipid levels.

  • Statins (e.g., Crestor, Lipitor). These drugs are the most effective cholesterol-lowering drugs available for reducing LDL cholesterol. If your LDL or total cholesterol is high, you will likely be prescribed a statin.
  • Bile acid resins, or bile acid sequestrants (e.g., Welchol, Colestid). These drugs are used mainly to lower LDL cholesterol, but they also modestly increase HDL cholesterol. Bile acid resins are sometimes prescribed in addition to a statin or instead of a statin in people who experience side effects with statins.
  • Niacin, or nicotinic acid (e.g., Niaspan). This is the most effective cholesterol medication for increasing HDL (“good”) cholesterol. It also lowers triglycerides.
  • Fibrates, orfibric acid derivatives (e.g., Tricor, Lopid). They are used mostly for lowering triglycerides, but they also increase HDL cholesterol.
  • Cholesterol absorption inhibitors (e.g., Zetia). This is a new class of cholesterol-lowering drug. So far, Zetia (or ezetimibe) is the only drug in this category that has been approved by the Food and Drug Administration (FDA). It lowers LDL cholesterol and is often prescribed along with a statin.

Not everyone who has high cholesterol levels will need to take medication. Treatment for high cholesterol always begins with diet and exercise, and some people are able to manage their cholesterol with diet and exercise alone. Even if you are taking medication for high cholesterol, it is still important to make lifestyle changes, such as eating a healthy diet and exercising regularly. One study showed that people who made such lifestyle changes in addition to taking medication were less likely to have heart problems (including heart attacks) than people who took medicine without making lifestyle changes.

Are women less likely to be screened or treated for high cholesterol?

Some research indicates that women are less likely than men to be screened for high cholesterol or treated with appropriate medication. In a study of people with heart disease, 35% of women compared with 55% of men received cholesterol-lowering medications.

How long does it take for cholesterol-lowering drugs to work?

Cholesterol-lowering drugs may lower your cholesterol within a few weeks. However, to get the full benefits in terms of lowering your risk of having a heart attack or dying from heart disease you have to take these medications for years and possibly the rest of your life. That’s why it’s very important that you continue taking your medication. Research shows that nearly half of all people prescribed a cholesterol-lowering medication stop taking it within three months; by 12 months about 60% of people have stopped taking their medication.6 If side effects from the medication are a problem, talk to your healthcare provider who may be able to lower your dose or switch you to a drug with fewer side effects.

Statins: Prescribed Statins

Statins (HMG-CoA Reductase Inhibitors) 
(check with manufacturer for specific information on each drug)

Generic:

Atorvastatin/ Fluvastatin / Lovastatin / Pravastatin/ Simvastatin /Rosuvastatin

Brands:

Lipitor / Lescol / Altocor / Mevacor / Pravachol / Zocor / Crestor

How they are given:

Oral (pill)

What they are used for:

  • Combined with diet and exercise to reduce LDL cholesterol, total cholesterol, triglycerides in people with high cholesterol
  • Reduces the risk of heart problems including heart attack in patients who do not have symptoms of heart disease
  • May slow down the buildup of fatty plaque in the arteries of the heart in people with heart disease

You should not them if:

  • You have liver disease or other liver problems

Possible side effects:

  • Constipation, nausea, abdominal pain, muscle pains, liver problems.
Pregnancy/ nursing:
  • Cholesterol is essential for healthy fetal development so you should not take statins if you are or may become pregnant. You should not take statins if you are nursing if treatment is essential then nursing should be discontinued.

What are statins?

Statins are among the most powerful cholesterol-lowering medications prescribed; they include atorvastatin (Lipitor) and simvastatin (Zocor). Statins reduce the production of cholesterol in the liver by inhibiting an enzyme called HMG CoA reductase; they are sometimes called HMG CoA reductase inhibitors. They are very effective at lowering total cholesterol and LDL (bad) cholesterol, making them the drug of choice for most women with high cholesterol. Statins also reduce the risk of dying or having a heart attack in women with heart disease, and they are increasingly prescribed to women at risk for heart problems even if their cholesterol levels are not very high. In 2003, million prescriptions were written for atorvastatin (Lipitor) alone, and an additional. 6 million for the next 3 most popular statins then available. Rosuvastatin (Crestor) was approved by the Food and Drug Administration (FDA) in August 2003.

How do statins affect cholesterol and triglyceride levels?

Combined results from 19 trials involving more than 50,000 people (23% were women) show that statins lower LDL (bad) cholesterol by 20% to 40%. This benefit was seen in women and the elderly, and across a wide range of LDL cholesterol levels. Some statins are better than others for lowering LDL cholesterol (See Which statin is best for lowering cholesterol? below) and the same statin is generally more effective at higher doses. Statins also lower total cholesterol by about 25% and triglycerides (another type of lipid that is associated with heart disease) by 15%.

Do statins prevent heart attacks or dying from heart disease in women with heart disease?

Yes. Studies show that statins lower the risk of dying from heart disease by 26%, and the risk of having a heart attack by 29% in women with heart disease even if their LDL cholesterol levels are not that high. In addition, women with heart disease treated with statins are 20% less likely to experience heart problems (including the need for a for angioplasty or bypass surgery) than women who do not take statins.

Do statins prevent heart attacks and death in women who do not have heart disease?

Studies have shown that statins prevent heart attacks and reduce the risk of dying from heart disease in men with high cholesterol who do not have heart disease. However, when the results of 6 large studies including more than 11,000 women were analyzed by gender, this benefit was not proven in women. This didn’t seem to make sense because statins lower cholesterol just as effectively in men and women, and there is no evidence that they work differently in men and women. The researchers believe that there were simply too few women and the studies were too short to show the full benefits of statins in women. Women have a lower risk of heart disease than men at any age and they live longer, so you have to study a lot more women for a much longer time to see whether statins have a statistically significant effect on heart attack and death rates. It is estimated that almost twice as many women than men without heart disease have to be treated with statins to prevent a single heart problem including heart attack (140 women compared with 77 men).

Some experts believe that one of the six studies, the ALLHAT study, was not as thorough as the other five. When the ALLHAT study was left out of the pooled analysis, statins were shown to lower the risk of dying or having a heart attack in women who did not have heart disease.

Do statins prevent stroke?

Yes. The Heart Protection Study found that simvastatin reduced the risk of any stroke by 25% in more than 20,000 people (25% were women) with diabetes, or blockages in their arteries including heart disease and cerebrovascular disease (blockages in the arteries in the head and neck). This benefit is mainly due to a reduction in the most common type of stroke (ischemic stroke) caused by a blood clot in the arteries of the brain. Statins do not seem to reduce the risk of bleeding in the brain (hemorrhagic stroke). Overall, a 39 mg/dL reduction in LDL (bad) cholesterol lowers the risk of any type of stroke by 21%. The benefits are even greater in men and women who have already suffered a stroke or mini stroke (transient ischemic attack or TIA). If you have a stroke, you will probably be prescribed a statin even if your cholesterol levels are not very high.

Do women with diabetes benefit from statins?

Men and women with diabetes who are considered at high risk for heart disease benefit from statins even if they do not already have heart disease, stroke, or high cholesterol. In one study of nearly 3,000 people with diabetes (32% were women) atorvastatin (10 mg) reduced the risk of stroke and heart problems including heart attack by 37%. Gender analysis showed that women with diabetes benefited as much as men. There were nearly 6,000 people with diabetes in the Heart Protection Study (30% were women); those treated with simvastatin were 25% less likely to die from heart disease or suffer a heart attack or stroke compared with those who got dummy pills. Again, women benefited just as much as men, as did people with relatively low LDL cholesterol levels (under 116 milligrams per deciliter [mg/dL]). Some of the men and women in these studies had heart disease or a history of stroke; others were considered high risk. The National Cholesterol Education Program Adult Treatment Panel III (ATP III for short) guidelines set a target LDL cholesterol of under 70 mg/dL for patients with diabetes and heart disease. However, it is not clear whether men and women with diabetes who are not otherwise high-risk for heart disease (usually young people without other risk factors such as high blood pressure or obesity) would benefit from taking statins.

Do statins help prevent osteoporosis?

Statins are not used to treat or prevent osteoporosis. Test tube and animal studies suggest that statins promote bone development, but it is not clear whether they help prevent bone fracture in people.

When researchers looked at more than 23,000 women enrolled in various studies (not necessarily statin studies), there was suggestive but not definitive evidence that women who took statins had a lower risk of hip and vertebrae fractures. However, in two large trials investigating the effects of statins on heart disease in more than 13,000 people (over 2,300 women), statins did not protect against hip fracture or other types of fracture in either men or women.

Which statin is best for lowering cholesterol?

Statin Dose for 30% to 40% LDL-Cholesterol Reduction

Drug

Dose (mg/day)

LDL-C reduction (%)

Atorvastatin

10

39

Fluvastatin

40-80

25-35

Lovastatin

40

31

Pravastatin

40

34

Simvastatin

20-40

35-41

Rosuvastatin

5-10

39-45

LDL-C = low density lipoprotein cholesterol; mg = milligram

Dose for dose, some statins are more powerful at lowering bad cholesterol than others. A standard dose generally refers to the amount that will lower LDL cholesterol by 30% to 40% (see table above). Which statin is best for you will depend on your cholesterol levels and your overall risk of having a heart attack or dying from heart disease. Cholesterol-lowering drugs are not a substitute for a healthy lifestyle; you must continue to eat a heart-healthy diet, exercise, and stop smoking (if you smoke) while taking your medication.

One study that directly compared four statins found that rosuvastatin (Crestor) reduced LDL cholesterol and total cholesterol more than atorvastatin, simvastatin, or pravastatin. There are safety concerns with the more powerful statins. Dose for dose, rosuvastatin is two to four times more potent than atorvastatin (the next most potent statin).

Are very high doses of statins better than regular doses?

Some experts believe the lower, the better for LDL (bad) cholesterol. With this in mind, studies have compared high doses of statins (80 mg atorvastatin or simvastatin) with regular doses (40 mg pravastatin or simvastatin) in men and women who suffered a heart attack or who have been diagnosed with heart disease. In women who had a heart attack, taking a high dose statin within 10 days reduced the risk of future heart problems such as heart attack or stroke compared with regular doses, but did not reduce the risk of dying. Women taking high dose statins suffered more side effects, including liver and muscle problems, than the women who took lower doses. Similar results were seen for men and women with stable heart disease who took either regular dose (10 mg) or high dose (80 mg) atorvastatin.

Because of the risk of side effects, women should only take high dose statins if regular doses (and lifestyle changes) do not lower their LDL cholesterol enough. If you are hospitalized for a heart attack, you may be given high dose therapy right away.

Why do I have to take another cholesterol-lowering medication in addition to a statin?

Your doctor may prescribe another cholesterol medication ( fibrates, bile acid resins, ezetimibe) or a diet that includes plant sterols and stanols in addition to a lower dose statin. This combination can lower LDL cholesterol by as much as 30% to 40%. Doubling the statin dose reduces LDL cholesterol by an extra 6% to 9%, and the risk of side effects increases with higher doses of statins. Some combinations of cholesterol-lowering medications, particularly statin-fibrate therapy (notably gemfibrozil [Lopid]) have a higher risk of muscle problems compared with a statin alone. Statins increase HDL (good) cholesterol levels by a small amount. If your HDL cholesterol is low, your doctor may prescribe an additional medication, usually niacin, as well as a statin.

Statins & CRP

In addition to lowering cholesterol, statins slow down the buildup of fatty plaque in the arteries of the heart ( atherosclerosis) and they lower levels of C-reactive protein(CRP). High CRP is a sign of inflammation, the body’s response to injury, and it is linked to a higher risk of heart disease. The aptly titled REVERSAL study found that heart disease patients who lowered their CRP levels the most with statins showed signs of reversing the fatty plaque buildup in the arteries of their hearts. The results were not analyzed separately for women but other studies have shown that statins lower CRP in women.

For people who have had a heart attack, lowering CRP reduces the risk of dying from heart disease or having another heart attack. In one study of nearly 4,000 heart attack patients (22% were women), those who lowered their CRP below 2 milligrams per liter (mg/L) were less likely to die or have another heart attack than those with higher CRP levels even if their LDL (bad) cholesterol did not fall below the target 70 mg/dL. The patients who lowered both LDL and CRP to target levels fared best. The results were not confirmed separately in women. Overall, intensive statin therapy (80 mg atorvastatin) lowered CRP and LDL cholesterol more than regular dose statin (40 mg pravastatin); however, there was a wide variation in how individual patients responded to these drugs. Previous research shows that statins do not lower CRP levels in some people.

It is not clear whether lowering CRP with statins has similar benefits in men and women who have not had a heart attack, but ongoing studies may provide an answer. Meanwhile, you are unlikely to be prescribed a statin for high CRP alone.

Muscle-related Side Effects

Overall statins are safe medications. The main side effects are muscle pain or weakness. This can be serious if there are signs that the muscle is breaking down your doctor will do tests to see if this is the case. In rare cases, this can develop into rhabdomyolysis, a potentially fatal condition in which muscle cells break down and release their contents into the bloodstream. Signs of rhabdomyolysis include muscle pain, swelling, or weakness, usually affecting the back or lower calves. Fever, nausea, dark urine, and a general feeling of discomfort may also occur. If you are taking statins and experience any of these symptoms, you should contact your healthcare provider immediately. The risk of muscle problems is higher if you are taking fibrates (another type of cholesterol-lowering drug) along with statins, and women have a higher risk than men when using both fibrates and statins. Medications for other conditions can also increase your risk for muscle-related side effects including cyclosporine, and certain antibiotics (such as erythromycin) or antifungals (such as itraconazole [Diflucan]). It is important that you always tell your doctor what other medications you are taking.

Rhabdomyolysis occurs in approximately 1 patient out of every 100,000 treated with statins, and accounts for less than 1 death per million statin prescriptions. However, some of the newer, more potent statins have a higher risk of this potentially fatal side effect. Cerivastatin (Baycol) was banned in the US in August 2001 after being linked to 31 such deaths. According to FDA figures, the incidence of rhabdomyolysis was 10 to 50 times higher for cerivastatin compared with other statins. The risks were higher at higher doses, and when cerivastatin was combined with the fibrate gemfibrozil (Lopid). Below are some factors that increase the risk of experiencing muscle problems when taking statins:

  • Older age especially over 80 years, and older women more than older men
  • Small body frame and frailty
  • Diabetic-related kidney problems
  • Taking multiple medications
  • Drinking large quantities of grapefruit juice (more than 1 quart/day)
  • Alcohol abuse

Rosuvastatin Side Effects & Dosing

Rosuvastatin (Crestor) is the most potent statin currently on the market. It was approved by the FDA in August 2003 at doses of 5 to 40 mg. Very high dose (80 mg) rosuvastatin was not approved by the FDA because it has a relatively high risk of the potentially fatal muscle-wasting side effect (rhabdomyolysis). A consumer group asked that rosuvastatin be banned after reports of this side effect with the approved doses. The FDA denied the request for a ban stating that Crestor does not pose a greater risk of muscle problems or rhabdomyolysis than the other statins when prescribed correctly. The FDA asked the manufacturers to revise the label for rosuvastatin to emphasize the increased risk at higher doses and in certain groups of patients including those taking fibrates. Specifically, patients taking the fibrate gemfibrozil (Lopid) should not take more than 10 mg of rosuvastatin, and the 40 mg dose should only be used in people who have already tried the 20 mg dose but their LDL cholesterol is still too high. Because studies show that Asians and Asian-Americans absorb almost twice as much of this drug into their blood than Caucasians (potentially increasing their risk for side effects), the FDA recommend a 5 mg starting dose for people of this race. Blood levels of rosuvastatin do not seem to differ between Caucasian, African American,,or Hispanic people.

Liver-related Side Effects

The other main side effect seen with statins is liver damage. Before you are prescribed a statin, your doctor will test your liver enzymes. These tests will be repeated at 12 weeks and then twice a year assuming no problems are found. If the blood tests show signs of liver damage, you will be taken off the statin; this usually resolves the problem.

Can statins prevent Alzheimer’s Disease & Dementia?

Fatty plaque buildup in the arteries of the brain and neck play a role in the development of dementia and Alzheimer’s disease (AD), and cholesterol is linked to the plaques found in the brains of people with AD. This led to theories that statins could help lower the risk of mental decline and AD. However, research shows that very low cholesterol levels appears to increase the risk of mental decline, and it is not clear whether statins have any affect (positive, negative) on mental function.

Some of the research so far suggests that statins reduce the risk of cognitive decline; in other studies, people taking statins experienced increased memory loss. Small trials suggest that statins may slightly lower attention and mental speed.

It is also unclear whether statins affect Alzheimer’s disease. The Cache County study followed more than 5,000 elderly residents (65 years or older) and saw no difference in the rates of dementia or AD between statin users and nonusers. Two large studies on the heart health benefits of statins have not shown any significant impact (either negative or positive) on mental function or dementia. The National Institues of Health (NIH) is sponsoring a large study on statins, mental function, and behavior that should shed more light on this issue.

Do statins increase the risk of cancer?

No. Studies from the early 1990s suggested but did not prove a link between low cholesterol and a higher risk of dying from cancer. However, the Heart Protection Study, which included 20,000 people (25% were women), found that those taking simvastatin had no increased risk of cancer. In addition, researchers combined the results of studies using various statins and found no increased risk of cancer for people who took statins for 5 years. It has also been shown that taking statins for 10 years does not increase your risk of cancer either. Now there is even a suggestion that taking statins may protect against some cancers, including colorectal cancer; however, this needs to be investigated more.

Is red yeast rice the same as a statin?

Red yeast rice is rice that is fermented with red yeast and used in Chinese cooking and herbal medicine. Red yeast rice is sold by many names, including the dietary supplements Cholestin and HypoCol, which claim to lower cholesterol. These preparations may contain a chemical (mevinolin) that is identical to the cholesterol-lowering drug lovastatin (Mevacor). In1998, the FDA banned Cholestin, deeming it an unapproved drug rather than a dietary supplement. In August 2007, the FDA warned customers to avoid red yeast rice products promoted on the internet because they could lead to severe muscle problems and kidney problems and interfere with other medications. Dietary supplements are not allowed to make claims to treat or cure disease. Drug manufacturers must prove to the FDA that their products are safe and effective before they can be sold in the US. Dietary supplements are not subject to such approval and there are no guarantees that they contain the ingredients listed on the label or that they have the promised effects. In small studies Cholestin has been shown to lower LDL (bad) cholesterol. An analysis of 10 commercially available red yeast rice products found that some did not contain any cholesterol-lowering ingredients. You should talk to your doctor before taking any dietary supplements. High cholesterol is a major risk factor for heart disease that should be treated with scientifically proven strategies (lifestyle changes and approved medications when necessary).

Bile Acid Resins : Prescribed Bile Acid Resins

Bile Acid Resins
(check with manufacturer for specific information)

Generic:

Colesevelam

Colestipol

Cholestyramine

Commonly prescribed brands:

WelChol

Colestid

Questran Cholybar

How they are given:

Powder, pill, or chewable bar

What they are used for:

To lower LDL (bad) cholesterol

You should not be treated with them if:

  • You have been diagnosed with a bowel obstruction
  • You have high triglycerides (more than 200 mg/dL)

Possible side effects:

Constipation, gas, nausea, stomach upset

Pregnancy/nursing:

The safety of these medications during pregnancy and nursing is not known, but they interfere with the body’s absorption of some vitamins which may harm fetal development

How do bile acid resins work?

Bile acids are made from cholesterol. Bile acid resins bind to bile acids in the intestines and the two are excreted from the body. Because bile acids are essential for digestion, your body makes up for the loss by converting blood cholesterol into bile acids. As a result, LDL (bad) cholesterol is removed from the blood and this lowers your LDL cholesterol level.

Bile acid resins are not absorbed by the body, so they have a low risk of serious side effects. Some bile acid resins interfere with the absorption of other medications and some vitamins. Be sure to tell your doctor of any over-the-counter or prescription medications you are taking before you start bile acid resins.

How do bile acid resins affect my cholesterol and triglyceride levels?

Bile acid resins are mostly prescribed to reduce levels of LDL (bad) cholesterol. Studies show that they lower LDL cholesterol by 15% to 20% in men and women with high cholesterol. Bile acid resins also slightly increase HDL (good) cholesterol by 3% to 8%. Colesevelam (WelChol) lowers LDL cholesterol more than cholestyramine or colestipol. Statins are the most effective cholesterol-lowering medications for reducing LDL cholesterol, so bile acid resins are used in people who cannot take statins because of side effects. Bile acid resins can also be combined with statins. Because bile acid resins may raise your triglyceride level slightly, you should not take them if you have high triglycerides (200 mg/dL or higher). Triglycerides are a type of lipid, or fat, that raises your risk of heart disease when present at a high level.

Do bile acid resins prevent heart disease and heart attacks?

There are no studies on the effectiveness of bile acid resins in preventing heart disease and heart attacks in women. Research in men with high cholesterol and/or heart disease found that bile acid resins reduce the risk of dying from a heart-related cause. In men with high cholesterol, bile acid resins reduced the risk of dying from heart disease by 24% and the risk of having a heart attack by 19%.

Why do I need to take a bile acid resin and a statin?

Your healthcare provider may prescribe a bile acid resin in addition to a statin. This helps to lower your LDL cholesterol further while avoiding some complications that are associated with high doses of statins [link to Statins]. When the two medications are used together, LDL cholesterol levels go down an extra 12% to 16% compared with taking a statin alone. Doubling the statin dose generally leads to an extra 6% to 9% reduction in LDL cholesterol, and the risk of side effects increases with higher statin doses.

What are the risks and side effects of bile acid resins?

The main side effects for bile acid resins are gastrointestinal complaints, particularly constipation. The biggest drawback to these medications is the large amount that you have to take. This is either in the form of a large tablet, chewable bar, or in a powder that can be mixed with water or juice (often these powders don’t taste good). Colesevelam seems to have fewer side effects than the other bile acid resins, and it does not affect the absorption of other medications you may be taking. For bile acid resins other than colesevelam, you will have to take additional medications one hour before or four hours after your bile acid resin.

Fibrates : Prescribed Fibrates

Fibrates
(check with manufacturer for specific information)

Generic:

Fenofibrate

Gemfibrozil

Commonly prescribed brands:

Tricor, Lofibra

Lopid

How they are given:

Pill

What they are used for:

To increase HDL (good) cholesterol and to lower triglyceride levels

You should not be treated with them if:

You have been diagnosed with:

  • Liver or kidney problems
  • Gall bladder disease

Possible side effects:

Indigestion, gas, bloating, diarrhea, constipation

Pregnancy/nursing:

  • The safety of these medications during pregnancy is unknown
  • Women who are nursing should not use these medications; if the treatment is essential, then nursing should be discontinued

How do fibrates work?

Fibrates activate a gene that causes the body to produce more of the two main components of HDL (good) cholesterol, which in turn increases your HDL cholesterol level. When that gene is activated, it also causes triglycerides to be broken down, lowering your triglyceride level. Triglycerides are another type of lipid that can increase your risk of heart disease if the levels are high.

How do fibrates affect my cholesterol and triglyceride levels?

Fibrates are prescribed mainly to treat high triglyceride levels (higher than 200 mg/dL). These medications can lower triglyceride levels by 20% to 50% in men and women with high triglycerides; the greatest reductions tend to occur in people with the highest levels. In some cases, fibrates can raise LDL (bad) cholesterol levels, so they are only used to treat high triglycerides in people with normal LDL cholesterol. In people with low triglycerides (less than 150 mg/dL), fibrates actually lower LDL cholesterol. Fibrates can also raise your HDL (good) cholesterol by 10% to 15%. The greatest increases in HDL cholesterol are seen in people with very high triglycerides and low HDL cholesterol (less than 40 mg/dL). Fibrates appear to work equally well in men and women.

Do fibrates lower my risk of heart disease and heart attacks?

A combined analysis of 17 fibrate studies that included nearly 30,000 men and women did not find that fibrates reduced the risk of dying early. This analysis included an older drug, clofibrate, that was actually shown to increase the risk of dying from non-heart-related causes (including cancer) in a large study in men. This drug is no longer prescribed, and subsequent studies of the other fibrates did not show a higher risk of dying from any cause.

Fibrates appear to lower the risk of experiencing heart problems including heart attack although there is not a lot of information on women. In studies in men with heart disease or high cholesterol, gemfibrozil reduced the risk of dying or having a heart attack by 22% to 34%. One large study that included both women and men found that, overall, the combination of fibrates and niacin reduced the risk of the risk of dying early by 26%. However, the results were not analyzed separately for men and women, so it is unclear whether women experience the same benefits from fibrates that men do.

Why do I need to take a fibrate and a statin?

Fibrates are not very effective at lowering LDL cholesterol and have even been shown to raise LDL cholesterol in some people. To counteract this, your healthcare provider may prescribe a statin in addition to a fibrate. This combination is used in people with high LDL cholesterol, low HDL cholesterol, and high triglycerides. Several studies have shown that this combination improves cholesterol and triglyceride levels in men and women. The lipid improvements are greater than those seen with a statin or fibrate alone. It is not yet known if combined statin/fibrate treatment will lower the risk of having a heart attack or dying from heart disease. Combining fibrates and statins increases the risks for certain serious side effects (see below).

What are the major risks of fibrate therapy?

Fibrates have been associated with an increased risk of developing muscle weakness ( myopathy). In rare cases, myopathy can develop into rhabdomyolysis, a potentially fatal condition in which muscle cells break down and release their contents into the bloodstream. Signs of rhabdomyolysis include muscle pain, swelling, or weakness, usually affecting the back or lower calves. Fever, nausea, dark urine, and a general feeling of discomfort may also occur. If you are taking fibrates and experience any of these symptoms, you should contact your healthcare provider immediately. The risk of both of these conditions increases when you take fibrates in addition to a statin. Women have a higher risk of myopathy than men when using both fibrates and statins. Gemfibrozil carries a higher risk of triggering rhabdomyolysis than fenofibrate (see Gemfibrozil versus fenofibrate).

Fibrates may cause liver problems; your healthcare provider will run blood tests before you take these medications and repeat them intermittently. If the blood tests show signs of liver damage, you will be taken off the fibrate, and this usually resolves the problem. Fibrates may also cause gallstones.

Gemfibrozil versus Fenofibrate

The risk of the potentially fatal side effect rhabdomyolysis is higher for gemfibrozil (Lopid) compared with fenofibrate (Tricor or Lofibra), particularly when combined with statins. This is because gemfibrozil appears to increase the levels of statins found in the blood, whereas fenofibrate has little or no effect on the blood levels of statins.

There are no large studies comparing fenofibrate and gemfibrozil; however, there is some evidence that fenofibrate is more effective at lowering triglycerides and LDL cholesterol, and raising HDL cholesterol. Fenofibrate was released in the US in 1998 and so far there are no studies showing it can reduce the risk of dying or having a heart attack.

Niacin : Niacin Formulations

Niacin
(check with manufacturer for specific information)

Types:

Immediate-release Long-acting Extended-release

Commonly prescribed brands:

Niacor
OTC also available
OTC
e.g. Slo-niacin
Niaspan

How it is given:

Pill

What it is used for:

Combined with diet, to reduce total cholesterol level, to lower triglyceride levels, and to increase HDL (good) cholesterol

You should not be treated with it if:

You have been diagnosed with:

  • Liver problems
  • Peptic ulcer
  • Arterial bleeding

Possible side effects:

Flushing (primarily in the face and neck), hot flashes, nausea, indigestion, gas, vomiting, diarrhea

Pregnancy/nursing:

  • The safety of this medication during pregnancy is unknown
  • Niacin is found in breast milk. Women who are nursing should not use these medications; if the treatment is essential, then nursing should be discontinued
OTC = over-the-counter

What is niacin?

Niacin is a form of vitamin B3 commonly found in meat, fish, legumes (peanuts), bread, and fortified breakfast cereals. Another form of vitamin B3 called nicotinamideis often confused with niacin, but it does not affect cholesterol levels. Niacin or nicotinic acid is the most effective medication for raising HDL (good) cholesterol. It is not clear exactly how niacin works. It seems to prevent the breakdown of the carriers for HDL cholesterol in the blood (called high-density lipoproteins).108 As a result, HDL cholesterol levels are increased in the blood. Niacin also decreases the production of the carriers for triglycerides in the blood (called very low-density lipoproteins). As a result, triglyceride levels are reduced. Triglycerides are another type of lipid, or fat, that can raise your risk of heart disease.

What types of niacin are available?

There are three types of niacin available:

  • Immediate-release or crystalline niacin is available over-the-counter, sometimes sold as vitamin B3 or simply niacin, or as the prescription drug Niacor
  • Long-acting niacin is sold over-the-counter. It is also called sustained-release or timed-release niacin
  • Extended-release niacin is only available by prescription as Niaspan

How does niacin affect my cholesterol levels?

Niacin is the most effective cholesterol medication for increasing HDL cholesterol, raising it twice as much as the fibrate gemfibrozil. A 1 to 2 g daily dose of niacin raises HDL cholesterol by 20% to 30% in men and women. Immediate-release niacin appears to be more effective than long-acting formulations, and just as effective as extended-release niacin at raising HDL cholesterol. Niacin also lowers triglycerides by about 15% to 35% at doses up to 2 g per day.

Niacin does not consistently lower levels of LDL (bad) cholesterol. Some studies show reductions of about 20% and others have found no LDL cholesterol-lowering effect for niacin. Because of the side effects (see below), a maximum dose of 2 g per day is generally recommended for niacin. It may be that higher doses are required to significantly lower LDL cholesterol in some people. Dose for dose, niacin lowers LDL cholesterol more in women than in men. Niacin may be combined with an LDL cholesterol-lowering medication (usually a statin). Even if niacin doesn’t actually lower LDL cholesterol, it can make it less likely to clog your arteries. Small dense LDL particles are more likely to clog your arteries than larger particles. Both extended-release and immediate-release niacin increase the proportion of larger particles compared with smaller ones. Additionally, niacin is the only cholesterol medication that lowers lipoprotein(a), or Lp(a), a type of LDL cholesterol that is associated with an increased risk of heart disease. Niacin can lower Lp(a) by 15% to 35% at doses of 1.5 to 2 g per day. It is not yet known whether lowering Lp(a) reduces the risk of having a heart attack or dying from heart disease.

Does niacin prevent heart attacks or dying from heart disease?

Niacin does not appear to reduce the risk of dying from heart disease. In men with heart disease, niacin reduced the risk of having another heart attack within five years. There have been no similar studies conducted in women.

Why do I need to take niacin and a statin?

Niacin is often used in combination with statins because the two medications affect different types of cholesterol. Statins lower LDL cholesterol, and niacin raises HDL cholesterol. One small study suggested that women taking a statin and immediate-release niacin have greater reductions in LDL cholesterol than men. Combined statin and niacin improves cholesterol and triglyceride levels more than a statin alone; however, it has more nuisance side effects. In contrast to fibrate/statin combined therapy, there does not appear to be an increase in the risk of serious side effects when statins and niacin are taken together.

Does combined niacin/statin therapy prevent heart attacks?

In studies in men, niacin combined with a medication to lower LDL cholesterol (a statin, fibrate, or bile acid resin), slowed the buildup of fatty plaque in the arteries of the heart. It is not known whether combination therapy with niacin and statins can lower the risk of having a heart attack or dying from heart disease. One study of around 550 men and women found that combined fibrates and niacin reduced the risk of the risk of dying early by 26%.

What is the niacin flush side effect?

The risks and side effects vary for the different types of niacin. The common nuisance side effect is the niacin flush characterized by warmth, redness, tingling, and possible itching in the face, neck, and chest. While this side effect is unpleasant, it is not serious. Flushing tends to occur shortly after you take your niacin dose and can last for a few hours. It is a particular problem with immediate-release niacin because of its rapid absorption and multiple daily doses (usually 2 or 3 pills per day). Flushing is less of a problem with long-acting niacin because it is generally absorbed over 12 hours and the niacin is slowly released into the bloodstream. Absorption rates and number of daily doses vary between long-acting products and preparations. Extended-release niacin (Niaspan) is absorbed over 8 to 12 hours, more quickly than long-acting niacin. However, because it is taken only once a day at bedtime, niacin is released when you are asleep and less likely to experience or notice flushing. To counteract the side effects of flushing and skin irritation, you can take a low-dose aspirin or non steroidal anti-inflammatory drug (such as Aleve, Advil, or Motrin) 30 minutes before your niacin dose. Hot drinks and alcohol should be avoided around the time of your niacin dose. You are less likely to experience flushing after several weeks of continued niacin use.

What other side effects does niacin have?

Niacin can cause liver problems particularly at high doses. Long-acting preparations have a higher risk of liver problems, including liver failure and hepatitis, than the other niacin preparations. Your healthcare provider will run blood tests to check for liver problems periodically. The risk of liver problems also increases if you switch between the different types of niacin without taking the proper precautions (see below).

Niacin may also affect blood sugar levels particularly at high doses (3 g per day), which can cause problems for people with diabetes. Lower doses of extended-release niacin (1 to 1.5 g per day) slightly increased blood sugar levels in people with diabetes in one study. However, these blood sugar effects were easily controlled when patients adjusted the doses of their diabetes medications.
A maximum daily dose of 2 g is generally recommended for all niacin preparations because this provides the best HDL cholesterol and triglyceride benefits while minimizing the risk of serious side effects.

Do men and women experience the same side effects?

One study found that women tended to experience more side effects than men with extended-release niacin, especially at higher doses (above 2 g). Another found that women and men both experienced flushing, but that women reported more nausea, vomiting, lack of energy, and rash than men. Men were more likely to report flu-like symptoms. To reduce the risk of gastrointestinal side effects, you can take niacin with a low-fat snack.

What is dose titration and can I switch between niacin preparations?

To reduce the number and severity of side effects, niacin doses are titrated. That means you start out taking a low dose (usually 500 mg) and gradually build up to the dose that’s most effective for you (usually 2g maximum). Your daily dose should not increase by more than 500 mg over a four week period. You should not switch between the different types of niacin without consulting your healthcare provider. When switching, you may have to start at a lower dose than you are used to and work up to a higher dose of the new formulation. Switching between immediate-release and long-acting niacin without taking the proper precautions can cause severe liver problems. Because there is some variation between the different long-acting niacin formulas, you should not switch between different brands.

Ezetimibe (Zetia) : Ezetimibe Formulations

Ezetimibe
(check with manufacturer for specific information on each drug)

Generic:

Ezetimibe

Ezetimibe/simvastatin

Commonly prescribed brands:

Zetia

Vytorin

How it is given:

Pill

What it is used for:

To lower LDL (bad) cholesterol, and total cholesterol

You should not be treated with it if:

You have been diagnosed with active liver disease and are currently taking a statin

Possible side effects:

No significant side effects have been found for ezetimibe alone. For combined treatment with statins, see statins side effects and risks.

Pregnancy/nursing:

  • The safety of this medication during pregnancy is unknown
  • Women who are nursing should not use this medication; if the treatment is essential, then nursing should be discontinued

What is ezetimibe?

Ezetimibe belongs to a new class of cholesterol-lowering medications called cholesterol absorption inhibitors. It is the first of these drugs to be sold in the US and was approved by the Food and Drug Administration (FDA) in October 2002. Ezetimibe prevents cholesterol from being absorbed in your small intestine. Because you need some cholesterol, your body must use cholesterol stored in the liver and take more cholesterol out of the bloodstream. The overall effect is that the LDL (bad) cholesterol and total cholesterol levels in your blood go down.

Currently, there is only one form of ezetimibe available, under the brand name Zetia. Another medication, sold as Vytorin, is a combination pill of ezetimibe and the statin simvastatin (Zocor).

How does ezetimibe affect my cholesterol levels?

When used alone, ezetimibe reduces LDL cholesterol levels by 18% and total cholesterol by 13% in men and women with high cholesterol. It increases HDL (good) cholesterol a little (about 1%) and lowers triglycerides (about 8%), another type of lipid that increases your risk of heart disease.

Does ezetimibe prevent heart attacks or dying from heart disease?

It is not yet known whether it can prevent heart disease or heart attacks. So far, no studies have been done in men or women to test for these effects.

Why do I need to take ezetimibe and a statin?

Ezetimibe is often prescribed along with a statin. This combination can be taken in a single pill (Vytorin) or as two separate prescriptions. Combining ezetimibe with a statin lowers LDL cholesterol an additional 12% to 14% compared with a statin alone. The benefits are the same for men and women. This combination therapy also lowers triglycerides an extra 10% compared with a statin alone and increases HDL (good) cholesterol by 2% to 5% more. LDL cholesterol levels may be reduced by 33% to 57% depending on the statin and the dose.

The ezetimibe/statin combination is not associated with the increased risk of serious side effects seen when another type of lipid-lowering drug, the fibrates, are combined with statins. Additionally, a low-dose combination (10 mg ezetimibe and 10 mg statin) is just as effective as the highest dose of statin at lowering LDL cholesterol. The risk of side effects increases for higher doses of statins; combining these two medications at lower doses instead may help some people avoid these problems.

Is ezetimibe combined with other cholesterol medications?

When cholesterol medications are combined, one of the drugs is usually a statin because these medications are the most effective for lowering LDL (bad) cholesterol and they reduce the risk of dying from heart disease. However, some people cannot take statins because of side effects, and other combinations may help them reach their cholesterol goals. When ezetimibe is combined with the fibrate fenofibrate (Tricor), LDL cholesterol is lowered by 20%.86 Total cholesterol, HDL cholesterol, and triglyceride levels also improve more than with ezetimibe alone.

What are the major risks and side effects of ezetimibe?

So far, no major risks or side effects have been found for ezetimibe. When ezetimibe is combined with a statin, the same risks and side effects that are seen for statins apply.

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