Diabetes and Lipid Clinic of Alaska

 

 


About Statins

Statins are a type of cholesterol-reducing drug that lower the levels of fats (lipids) in the blood, including cholesterol and triglycerides. Statins work by blocking the production of a specific enzyme used by the body to make cholesterol. They are effective in lowering blood fat levels in patients with of high cholesterol (hypercholesterolemia) and are therefore helpful in the prevention of coronary, cerebrovascular and peripheral vascular disease.

Other types of cholesterol reducing drugs include fibrates, bile acid resins, nicotinic acid and ezetimibe. All are commonly used to treat high cholesterol, but statins are considered the first line of treatment for patients with this condition.

While all cholesterol–lowering drugs are effective to some degree in lowering blood fat levels, statins are particularly effective at lowering levels of LDL “bad” cholesterol and – to a lesser degree – triglycerides. Statins have been shown to decrease LDL levels between 30 and 60 percent, depending on the kind of statin and the dosage. While statins do increase levels of HDL “good” cholesterol, they do not seem to increase those levels as well as nicotinic acid.

Recent studies suggest that statins have a mild anti–inflammatory action and may reduce blood levels of C-reactive protein, an indicator of inflammation in the body. C–reactive protein is proving to be a useful “marker” for predicting heart disease and stroke, which are associated with inflammation of the blood vessel walls.

There are currently 7 statins approved for sale in the United States. They are:

Atorvastatin*  Pravastatin*
Fluvastatin*  Rosuvastatin
Lovastatin* Simvastatin*
Pitavastatin  
 
*Generic available     


Although the statins are used interchangeably to reduce LDL cholesterol, studies have shown differences in the degree of effectiveness and the possible side effects associated with various statins. In particular, rosuvastatin has shown the greatest ability to reduce LDL cholesterol, while low–dose fluvastatin is the least potent statin. Because side effects tend to occur at higher dosages, the goal of therapy to find the lowest dose of the least potent statin that yields acceptable results.

Potential side effects of Statins

There are a number of side effects that could occur as a result of taking statins. For example, muscle aches and tenderness are side effects that must be immediately reported to a physician. Another effect is the development of abnormal liver function, which is diagnosed by a liver enzyme test. Patients should also notify their physician if they experience any of the side effects listed below. While these side effects may be seen in some individuals, they are not common. They include:

  • Allergic reaction
    (new onset of wheezing, respiratory congestion, itching or skin rashes)
  • Excessive gas or belching
  • Decreased sexual interest or ability
  • Headache
  • Difficulty sleeping
  • Heartburn or indigestion
  • Constipation
  • Abdominal pain
  • Diarrhea
  • Nausea or vomiting
  • Dizziness or lightheadedness
  • Skin rash


A very rare, but potentially fatal, side effect of statins is rhabdomyolysis, a severe muscle reaction. Rhabdomyolysis is a condition in which muscle cells break down, releasing their contents into the bloodstream. It most often affects the muscles in the back or lower calves. Some patients report no symptoms, and in rare cases rhabdomyolysis can lead to kidney or other organ failure and death. Patients should report any of the following symptoms of rhabdomyolysis to their physicians immediately:

  • Muscle cramps, pain, swelling, weakness, stiffness and/or tenderness
  • Fever
  • Dark urine
  • Nausea and/or vomiting
  • Malaise (a general feeling of illness or discomfort)

Physicians monitor for this condition by measuring the blood level of the muscle enzyme called creatine phosphokinase (CPK). Risk of this severe complication appears to be higher in elderly patients, those taking high doses of statins and those taking statins in conjunction with other cholesterol-reducing drug called fibrates, particularly Lopid (gemfibrozil). In August 2001, one type of statin, called cerivastatin (brand name “Baycol”), was voluntarily withdrawn from the market by its manufacturer due to reports that fatal cases of rhabdomyolysis had been significantly more common with cerivastatin than with other approved statin drugs.

Drugs and other interactions with Statins


Patients should consult their physician before taking any other medication (either prescription or over–the–counter) or nutritional supplements. Of particular concern to patients taking statins are:

  • Other cholesterol-reducing drugs. Taking more than one cholesterol reducer at a time may worsen side effects, unless physicians have prescribed a specially dosed combination of medications. One fibrate called gemfibrozil is of particular concern since taking gemfibrozil with a statin may increase the patient’s risk of developing a rare, but potentially fatal side effect called rhabdomyolysis. For more information on rhabdomyolysis see Potential side effects.

  • Inotropes (e.g., digoxin). Medications that strengthen the heart’s contractions so that it can pump more blood per minute. Use with atorvastatin, fluvastatin, or simvastatin may increase blood levels of inotropes, increasing the potential for side effects.

  • Birth control pills. Use with atorvastatin may increase the blood levels of the hormones used in birth control pills, increasing the risk of side effects.

  • Calcium channel blockers. Medications that block the movement of calcium ions into heart cells and blood vessels. This increases the supply of oxygen–rich blood to the heart, lowers blood pressure and reduces the heart's workload. Use with simvastatin may increase the risk of muscle problems.

  • Protease inhibitors. Medications used in the treatment of human immunodeficiency virus (HIV). Use with simvastatin may increase the risk of developing kidney failure or muscle problems.

  • Azole antifungals (systemic antifungals). Medications used to treat serious fungal infections that may occur in various body regions. They may be taken orally in pill form or may be injected. Using some statins and azole antifungals in combination may increase an individual’s risk of developing muscle problems (rhabdomyolysis) that can lead to kidney failure.

  • Immunosuppressants. Medications used to reduce the body’s immune system that are often prescribed following an organ transplant (e.g. heart transplant) to prevent the body from rejecting the donor organ. Taking statins with immunosuppressants may increase an individual’s risk of developing rhabdomyolysis.

  • Erythromycins. A type of antibiotic used in the treatment of infections. Using some statins in combination with erythromycins may increase an individual’s risk of developing rhabdomyolysis.

  • Grapefruit juice. Grapefruit juice interferes with the liver’s ability to break down (metabolize) some statins. Consequently, the medication cannot reach its intended “target.” This, in turn, can cause a toxic build–up of the statins (especially atorvastatin and simvastatin in the blood. While the buildup is less likely if the juice is ingested four or more hours prior to the medicine, patients taking statins are advised to refrain from drinking grapefruit juice. Patients may also be instructed to avoid eating grapefruit.

Ongoing research regarding Statins

Researchers continue to evaluate the role of statins in high cholesterol treatment and the prevention of heart disease. Some of the more recent findings include:

  • Simvastatin, when used in combination with niacin nicotinic acid can significantly lower the risk of heart attack, stroke and heart related death.

  • Statins may reduce blood levels of C-reactive protein (CRP). CRP is a substance produced by the liver in response to any inflammation (an inflammatory marker). CRP is the only inflammatory marker that has been found to be an indicator of heart health. Very high levels of CRP are found in the blood of patients who are having a heart attack or unstable angina symptoms. Mildly elevated CRP levels have been found in people with diabetes, glucose intolerance and high blood pressure (hypertension), all of which are independent risk factors for heart disease.

  • Statins are thought to have mild anticoagulant properties, with an ability to help prevent blood clots.

  • Study results find that statins significantly reduce the rates of death and coronary events in elderly patients. This is important, as other research has revealed that statins are under–used in the elderly population.

  • Diet may be as effective as taking statins in lowering blood cholesterol levels. Even so, other research has shown that in those patients with equivalent lowering of cholesterol through diet or with statins, fewer cardiac events occur in the statin–treated patients. This demonstrates that the beneficial effects of statins are related not only to their lipid effects, but also to other factors.

  • Statins may slow production of a protein (amyloid) associated with Alzheimer’s disease. Alzheimer’s disease involves a buildup of plaque that eventually distorts the structural design of the brain. While the trial involved guinea pigs, it could have a significant impact on future Alzheimer’s disease research.

  • Giving high doses of statins to patients immediately following a heart attack or episode of unstable angina may reduce the risk of another coronary event in the future. This benefit has been seen even among patients whose blood cholesterol levels were not extremely high.

  • One statin (pravastatin) has been found to lower the risk of developing type 2 (adult onset) diabetes and stroke, as well as reducing cholesterol levels.

  • In addition to lowering LDL levels, statins have shown to slow the process of calcification, the hard buildup of calcium deposits on the walls of an artery. Calcification is one of the factors involved in hardening and narrowing of arteries (atherosclerosis) and, if severe enough, may be associated with blockages.

  • Research has suggested that cholesterol–reducing drugs can benefit patients with coronary artery disease who have an implantable cardioverter defibrillator (ICD). Cholesterol–lowering therapy may have an anti–arrhythmic effect, which can result in fewer recurring episodes of ventricular tachycardia and ventricular fibrillation and less firing of the ICD.

  • The Heart Protection Study demonstrated significant benefits of statins (e.g., lower risk of heart attack and stroke) in patients with heart disease, peripheral vascular disease and/or diabetes. These benefits occurred in patients with both high and normal levels of cholesterol.

  • Statins have been found to improve symptoms of claudication associated with peripheral vascular disease.

  • Statins have been shown to reduce the chance of heart attack and stroke among patients with diabetes, even if they have normal cholesterol levels. As a result, the American Diabetes Association recommends statins for diabetics over the age of 40 who have a total cholesterol greater than 135.

  • Contrary to earlier claims, statins do not offer protection against macular degeneration, an untreatable cause of blindness that can occur with advancing age

Lifestyle considerations with Statins

Some cholesterol reducers can cause liver inflammation, which tends to resolve on its own after patients stop taking the medication. To monitor this and other complications, patients should undergo regular blood tests and liver function tests.

Some statins (e.g., lovastatin) work better when taken with food. Patients should carefully follow the directions for taking their medication provided by their physician and pharmacy. Those who miss a dose of this medication should take it as soon as possible, unless it is nearly time for the next dose. In that case, the missed dose should be skipped. Double doses of this medication should NOT be taken.

Women taking cholesterol–reducing drugs should inform their physicians at once if they are – or plan to become – pregnant, as cholesterol is an important contributor to the development of the fetus. Statins are excreted in breast milk, and are therefore not recommended for nursing mothers.

Patients should not abruptly stop or the change the dosage and timing of their medications without first consulting their physicians. It is also important that patients notify all physicians (including dentists) that they are taking statins before undergoing any surgical procedure.

Most patients on medication to treat high cholesterol (hypercholesterolemia) will be taking it for the rest of their lives, provided no serious side effects occur. Patients should remember that medications may control high cholesterol, but they do not cure it. Patients should continue to take their medication exactly as directed, eat a heart-healthy diet that is low in saturated fats and keep all scheduled follow–up appointments with their physician.

Pregnancy use issues with Statins


Pregnant women or women planning to become pregnant in the near future are advised not to take statins. These medications block the formation of cholesterol, which is needed for the fetus to properly develop. Statin use during pregnancy could lead to birth defects or miscarriages. Women who think they may have become pregnant while taking this medication should contact their physicians immediately. Statins are also not recommended for women who are breast feeding.

For more information, please consult with the medical professionals at Diabetes and Lipid Clinic of Alaska.

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