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Statin drugs are very effective for lowering LDL cholesterol levels and are among the safest and most studied medicines available today.

Potential side effects include muscle weakness and muscle pain (myopathy), which are partly genetically determined (read the study).

Lifestyle changes are key to lowering cholesterol, whether you take a statin or not – Knowing your genetic risk for statin induced myopathy may be your key to successful statin therapy

A heart-healthy lifestyle reduces risk of heart disease and stroke more than any medication alone

Adhering to a heart-healthy lifestyle is the single most important strategy for reducing your risk of heart disease, whether you take a statin or not. Eating a healthy diet, not smoking, managing body weight, and exercising regularly are examples of lifestyle changes that will not only improve cholesterol levels, but many other risk factors for heart disease as well. Lifestyle changes may have a greater impact on reducing risk of heart disease and stroke than any medication alone.

For some people, lifestyle changes are not enough to lower cholesterol

In spite of adhering to a heart-healthy lifestyle, some people need further treatment for elevated blood cholesterol levels. The American Heart Association recommends cholesterol-lowering therapy for individuals who after therapeutic lifestyle changes, still have high LDL cholesterol levels (above 130 -190 mg/dL). The LDL cholesterol level for drug consideration and dosing varies, depending on the presence or absence of other risk factors for heart disease.

When medication is needed to lower LDL cholesterol, statins are a doctor´s first choice

The drugs of first choice to lower LDL cholesterol are statins, also known as hydroxy-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors, because they block the HMG CoA reductase enzyme in the liver that is responsible for making cholesterol. Statin drugs are very effective for lowering LDL cholesterol levels and are among the safest and most studied medicines available today.

Potential side-effects of statins include muscle problems (myopathy)

Like all medicines, statins carry potential side effects, but they are usually mild, easy to recognize, reversible and very rarely dangerous. These are for example:

• upset stomach or nausea
• diarrhea
• vomiting
• constipation
• headache
• rash

Muscle pain and weakness (myopathy), are also potential side-effects, ones that are partly genetically determined by a sequence variant in the SLCO1B1 gene on chromosome 12. The deCODEme Complete Genetic Scan identifies this variant and provides an estimate of the risk of developing myopathy when taking statin drugs for individuals of European descent.

The most serious (but very rare) type of muscle problem associated with statin drugs is Rhabdomyolysis. It often begins as muscle pain but can progress to loss of muscle cells, kidney failure, and even result in death. It occurs more often when statins are used in combination with other drugs that themselves cause Rhabdomyolysis or with drugs that prevent the elimination of statins and raise the levels of statins in the blood.

There are many different types of statins

All statins lower cholesterol by blocking the HMG CoA reductase enzyme in the liver that is responsible for making cholesterol. But different types of statins have slightly different chemical structures. This means that if you experience side-effects from one statin, you might not from another. Resolving statin-induced myopathy is therefore often achieved by doctors, simply by prescribing a different type of statin for their patients. The different types of statin drugs currently available, include:

• atorvastatin (Lipitor)
• fluvastatin (Lescol)
• lovastatin (Mevacor)
• pravastatin (Pravachol)
• rosuvastatin (Crestor)
• simvastatin (Zocor)

The various types of statins differ in several ways, both in their ability to reduce cholesterol and in the frequency with which they cause side effects. For example a statin called Cerivastatin (Baycol) was withdrawn from pharmacies worldwide in 2001 because it caused the the severe but rare Rhabdomyolysis more often than other statins.

Any decision to initiate or switch statin medications, should be taken only in consultation with your doctor.

Risk factors for statin-induced myopathy

Although a significant genetic risk factor has now been identified, it is still not fully understood why only some individuals develop myopathy in response to statins. Any factor that increases the concentration of a statin in the blood however, has the potential to increase the risk of myopathy. The following risk factors for statin-induced myopathy have been identified:

• High-dose statin treatment. The risk of developing myopathy increases with higher doses of statins.
• Other drugs taken in combination with statins can increase risk of developing myopathy, for example cyclosporine or amiodarone (see more on interaction with other drugs below).
• Advanced age – individuals over 80 years of age have a higher risk.
• Sex – females have a higher risk than males.
• Low body mass index, being frail with a small body frame increases risk.
• Diabetes, and diseases affecting kidney or liver function can predispose to statin-induced myopathy
• Hypothyroidism (untreated) is a common cause of hypercholesterolemia and raised creatine kinase, and may increase risk of statin induced myopathy.
• Vigorous exercise. Active people may be more likely to develop problems from statin use than those who are sedentary.
• Excess alcohol intake.
• Diet, especially excessive grapefruit or cranberry juice consumption.
• Genetic factors.

Prevention and Treatment

Preventing statin-induced myopathy

Even if you begin drug treatment to lower your cholesterol, you should implement cholesterol-lowering lifestyle changes as well. This will keep the dose of statin drugs you need as low as possible, and lower your risk in other ways as well.

If you are about to start statin therapy, and have any of the above risk factors, your doctor may start you with a low dose of statin. This may slowly be increased up to the dose required to get your cholesterol to a safe level. During this process, it is likely that you will be closely monitored for possible problems.

If symptoms such as muscle weakness or pain arise after starting to take statins, creatine kinase (a protein needed for chemical reactions that produce energy for muscle contractions) is measured to assess severity of muscle damage and to aid in deciding whether to continue treatment. However, routine monitoring of creatine kinase in individuals taking statins with no symptoms of muscle weakness or pain is not recommended. This is because many factors can affect levels of creatine kinase.

Treating statin-induced myopathy is often as simple as switching statins

Following a diagnosis of statin-induced myopathy, the first line of treatment typically implemented by physicians is to stop administering statins, observe symptoms, and monitor creatine kinase levels.

If symptoms subside, and if benefits outweigh the risks, physicians may try to start their patients on statins again at lower doses and assess whether features of statin induced myopathy return. Many individuals tolerate the same statins, however at a lower dose, after symptoms resolve. Alternatively, another class of cholesterol lowering drug might need to be considered.

Please note that it is essential that any decisions about statin therapy be taken in consultation with a physician.

More information

Statins can interact with other drugs

Statins can also interact with other drugs, thereby causing adverse effects. One type of interaction disturbs the elimination of statins by the liver. Liver enzymes are responsible for eliminating all statins from the body, except pravastatin and rosuvastatin. Drugs that block the action of these liver enzymes can increase the levels of these statins in the blood and thereby increase the potential for muscle problems.

Drugs or agents that interact with statins in this way include some frequently used antibiotics (such as erythromycin, clarithromycin), antifungals (such as itraconazole), heart medications (such as diltiazem and verapamil).

Grapefruit and grapefruit juice also contain chemicals that interfere with liver enzymes in this way, and should therefore be avoided when taking statins.

For more information on high cholesterol and statin-induced myopathy, talk to your doctor and visit the following websites:

• About Statins from MedlinePlus
• About Cholesterol – LDL and HDL Cholesterol: What’s Bad and What’s Good – American Heart Association
• Cholesterol-lowering drugs – American Heart Association
• FDA – High cholesterol – Medicines to help you
• FDA – Public Health Advisory on Crestor
• FDA – Controlling Cholesterol with Statins
• High Blood Cholesterol – What you need to know, from the national Heart, Lung, and Blood Institute
• Statin side effects – from the Mayo Clinic
• Drug Information -Up-to-date information on prescription and over-the-counter medications
• Drug Side Effects -Gets the latest consumer alerts about medication side effects

This content was last reviewed on February 09, 2010.

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