What are statins, and how do they work?
"Statins" is a class of drugs that lowers the level of cholesterol in the blood by reducing the production of cholesterol by the liver. (The other source of cholesterol in the blood is dietary cholesterol.) Statins block the enzyme in the liver that is responsible for making cholesterol. This enzyme is called hydroxy-methylglutaryl-coenzyme A reductase (HMG-CoA reductase). Scientifically, statins are referred to as HMG-CoA reductase inhibitors.
Cholesterol is critical to the normal function of every cell in the body. However, it also contributes to the development of atherosclerosis, a condition in which cholesterol-containing plaques form within arteries. These plaques block the arteries and reduce the flow of blood to the tissues the arteries supply. When plaques rupture, a blood clot forms on the plaque, thereby further blocking the artery and reducing the flow of blood. When blood flow is reduced sufficiently in the arteries that supply blood to the heart, the result is angina (chest pain) or a heart attack. If reduced flow is caused by plaques in the arteries of the brain, the result is a stroke. If reduced flow is caused by plaques in the arteries of the leg, they cause intermittent claudication (pain in the legs while walking). By reducing the production of cholesterol, statins are able to slow the formation of new plaques and occasionally can reduce the size of plaques that already exist. In addition, through mechanisms that are not well understood, statins may also stabilize plaques and make them less prone to rupturing and develop clots.
The important role of cholesterol in atherosclerosis is widely accepted by scientists. Research from the last few years shows that aggressive cholesterol reduction is more beneficial than modest reductions. Nevertheless, atherosclerosis is a complex process that involves more than just cholesterol. For example, scientists have discovered that inflammation in the walls of the arteries may be an important factor in in the development of atherosclerosis. In addition to lowering cholesterol levels, statins also reduce inflammation, which could be another mechanism by which statins beneficially affect atherosclerosis. This reduction of inflammation does not depend on statins' ability to reduce cholesterol. Furthermore, these anti-inflammatory effects can be seen as early as two weeks after starting statins.
What are some examples of statins?name="what_are_some_examples_of_statins">
What are some examples of statins?
Statins that are approved for use in the U.S. include:
Quick GuideLower Your Cholesterol, Save Your Heart
For what conditions are statins used?
Risk factors for atherosclerosis include:
- Abnormally elevated cholesterol levels
- A family history of heart attacks (particularly at a young age)
- Increasing age
- High blood pressure
Most individuals are placed on statins because of high levels of cholesterol. Though reduction of cholesterol is important, heart disease is complex and, as discussed previously, other factors such as inflammation may play a role. Thirty-five percent of individuals who develop heart attacks do not have high blood cholesterol levels, yet most of them have atherosclerosis. This means that high levels of cholesterol are not always necessary for atherosclerotic plaques to form.
Because it is not clear which effect of statins is responsible for their benefits, the goal of treatment with statins should not be only the reduction of cholesterol to normal levels, but rather the prevention of the complications of atherosclerosis (angina, heart attacks, stroke, intermittent claudication, and death). This concept is important because it allows for individuals who have or are at risk for atherosclerosis, but do not have high levels of cholesterol to be considered for treatment with statins. Statins, like angiotensin converting enzyme inhibitors (ACE inhibitors), are an important class of drugs because they have been shown to reduce the incidence of heart attacks, strokes, and death.
What are the side effects of statins?
The most common side effects are:
The most serious side effects are liver failure and rhabdomyolysis (injury or death of muscle tissue). Serious liver damage caused by statins is rare. More often, statins cause abnormalities of liver tests. Abnormal tests usually return to normal even if a statin is continued, but if the abnormal test value is greater than three times the upper limit of normal, the statin usually is stopped. Liver tests should be measured before statins are started and if there is a medical concern about liver damage thereafter.
Rhabdomyolysis is a rare serious side effect which involves damage to muscles. Rhabdomyolysis often begins as muscle pain and can progress to loss of muscle cells, kidney failure, and 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. Since rhabdomyolysis may be fatal, unexplained joint or muscle pain that occurs while taking statins should be brought to the attention of a health care professional for evaluation. Statins must not be used during pregnancy because of the risk of serious adverse effects to the developing fetus.
Statins have been associated with increases in HbA1c and fasting serum glucose levels that are seen in diabetes.
There are also post-marketing reports of memory loss, forgetfulness, amnesia, confusion, and memory impairment. Symptoms may start one day to years after starting treatment and resolve within a median of three weeks after stopping the statin.
With which drugs do statins interact?
Statins have some important drug interactions. The first type of interaction involves the enzymes responsible for the elimination of statins by the liver. Liver enzymes (specifically, the cytochrome P-450 liver enzymes) are responsible for eliminating all statins from the body with the exception of pravastatin and rosuvastatin. Therefore, drugs that block the action of these liver enzymes increase the levels of simvastatin, lovastatin, fluvastatin, and atorvastatin (but not pravastatin or rosuvastatin) in the blood and can lead to the development of rhabdomyolysis. Drugs or agents that block these enzymes include:
- protease inhibitors, for example, indinavir (Crixivan), ritonavir (Norvir) used in treating AIDS)
- erythromycin (E-Mycin)
- itraconazole, (Sporanox)
- clarithromycin, (Biaxin)
- telithromycin (Ketek)
- cyclosporine (Sandimmune)
- boceprevir (Victrelis)
- telaprevir (Incivek)
- voriconazole (Vfend)
- diltiazem, (Cardizem, Dilacor, Tiazac)
- verapamil (Calan, Verelan, Verelan PM, Isoptin, Isoptin SR, Covera-HS)
- ombitasvir/paritaprevir/ritonavir and dasabuvir (Viekira Pak)
- grapefruit juice (> one quart daily)
Lovastatin and simvastatin should not be combined with the following drugs:
- ketoconazole (Nizoral, Extina, Xolegel, Kuric)
- danazol (Danocrine)
- protease inhibitors
- amiodarone (Cordarone)
- amlodipine (Norvasc)
- ranolazine (Ranexa)
Another important drug interaction occurs between statins and niacin and fibric acids, for example, gemfibrozil (Lopid), clofibrate (Atromid-S), and fenofibrate (Tricor). Niacin and the fibric acid drugs (lipid-lowering agents) can cause rhabdomyolysis or liver failure when used alone, and combining them with statins increases the likelihood of rhabdomyolysis or liver failure. Gemfibrozil should not be combined with statins. Other fibric acids and niacin are used, with caution, in combination with statins.
Cholestyramine (Questran) as well as colestipol (Colestid) bind statins in the intestine and reduce their absorption into the body. To prevent this binding within the intestine, statins should be taken one hour before or four hours after cholestyramine or colestipol.
Stains increase the effect of warfarin (Coumadin). Patients taking statins and warfarin should have their blood clotting ability monitored carefully.
Statins should not be combined with red yeast rice because red yeast rice contains a chemical that is similar to statins. Combining red yeast rice with statins can lead to serious side effects such as muscle breakdown (myopathy).
Are there differences among statins?
Statins differ in several ways. The most obvious difference is in their ability to reduce cholesterol. Currently, atorvastatin (Lipitor) and rosuvastatin (Crestor) are the most potent, and fluvastatin (Lescol) is the least potent.
The statins also differ in how strongly they interact with other drugs. Specifically, pravastatin (Pravachol) and rosuvastatin (Crestor) levels in the body are less likely to be elevated by other drugs that may be taken at the same time as the statins. This is so because the enzymes in the liver that eliminate pravastatin and rosuvastatin are not blocked by many of the drugs that block the enzymes that eliminate other statins. This prevents the levels of pravastatin and rosuvastatin from rising and leading to increased toxicity such as myopathy (inflammation of the muscles). For example, in scientific studies, patients who took both verapamil (Calan, Verelan, Verelan PM, Isoptin, Isoptin SR, Covera-HS) and simvastatin (Zocor) experienced myopathy 10 times more often than patients who received simvastatin alone because verapamil increased the blood levels of simvastatin.
Statins differ in the frequency with which they cause a severe type of myopathy called rhabdomyolysis, in which muscles are severely damaged. Cerivastatin (Baycol) was withdrawn from pharmacies worldwide because it caused rhabdomyolysis 10 to 100 times more often than other statins. Rhabdomyolysis may occur more often in patients taking statins with drugs that also cause rhabdomyolysis or drugs that increase the blood concentration of the statin.
Reference: FDA Prescribing Information
Serious side effects can occur.
Examples of statins available in the US are
- atorvastatin (Lipitor),
- fluvastatin (Lescol, Lescol XL),
- lovastatin (Mevacor, Altoprev),
- pravastatin (Pravachol),
- rosuvastatin (Crestor),
- simvastatin (Zocor), and
- pitavastatin (Livalo).
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Cataract SurgeryCataract surgery is a surgical procedure in which a small incision is made in the surface of the eye in or near the cornea and a thin ultrasound probe is inserted into the eye so ultrasonic vibrations can dissolve the clouded lens. These tiny pieces are sucked out through the probe and an artificial lens is placed in the space the cataract occupied.
Cholesterol SlideshowDo you know the different cholesterol levels and what they mean? Learn the alphabet soup of cholesterol testing: LDL, HDL, good, bad, and triglycerides. Pictures show tests, treatments, and critical foods from eggs to avocados.
Cholesterol PictureCholesterol carried in particles of low density (LDL cholesterol) is referred to as the "bad" cholesterol because elevated levels of LDL cholesterol are associated with an increased risk of coronary heart disease. See a picture of Cholesterol and learn more about the health topic.
Cholesterol TestA cholesterol blood test measures the amount of cholesterol in the body. There are two types of cholesterol; the "good" cholesterol or HDL, and the "bad" cholesterol or LDL. High cholesterol levels in the blood can lead to heart attack, stroke, and peripheral vascular disease. Learn more about cholesterol tests and how to interpret them.
Fatty LiverNonalcoholic fatty liver disease occurs due to the accumulation of abnormal amounts of fat within the liver. Fatty liver most likely caused by obesity and diabetes. Symptoms of fatty liver disease are primarily the complications of cirrhosis of the liver; and may include:
- mental changes,
- liver cancer,
- the accumulation of fluid in the body (ascites, edema), and
- gastrointestinal bleeding.
- weight loss, and
- bariatric surgery.
Heart Disease (Coronary Artery Disease)
Heart disease (coronary artery disease) occurs when plaque builds up in the coronary arteries, the vessels that supply blood to the heart. Heart disease can lead to heart attack. Risk factors for heart disease include:
- High blood pressure
- High cholesterol
- Family history
Angina, shortness of breath, and sweating are just a few symptoms that may indicate a heart attack. Treatment of heart disease involves control of heart disease risk factors through lifestyle changes, medications, and/or stenting or bypass surgery. Heart disease can be prevented by controlling heart disease risk factors.
CAD SlideshowWhat is heart disease (coronary artery disease)? Learn about the causes of heart disease. Symptoms of heart disease include chest pain and shortness of breath. Explore heart disease diagnosis, treatment, and prevention.
Heart Disease QuizTake our Heart Disease Quiz to get answers and facts about high cholesterol, atherosclerosis prevention, and the causes, symptoms, treatments, testing, and procedures for medically broken hearts.
Heart SymptomsHeart attacks symptoms vary greatly for men and women, from anxiety and fatigue to nausea and sweating. Learn the warning signs of a heart attack and know the symptoms that may require an immediate trip to the hospital.
Liver Blood TestsAn initial step in detecting liver damage is a simple blood test to determine the presence of certain liver enzymes in the blood. Under normal circumstances, these enzymes reside within the cells of the liver. But when the liver is injured, these enzymes are spilled into the blood stream, and can lead to diseases like fatty liver, type 2 diabetes, obesity, and hepatitis. Several medications also can increase liver enzyme test results.
Liver DiseaseLiver disease can be cause by a variety of things including infection (hepatitis), diseases such as:
- high cholesterol or triglycerides,
- blood flow obstruction to the liver, and
- toxins (medications and chemicals).
- upper right abdominal pain, and
Lower Cholesterol TipsNeed to lower your cholesterol levels? Use these smart diet tips to quickly and easily lower your blood cholesterol levels. Choose heart-healthy foods to lower cholesterol and improve your heart health.
Peripheral NeuropathyPeripheral neuropathy is a problem with the functioning of the nerves outside of the spinal cord. Symptoms may include numbness, weakness, burning pain (especially at night), and loss of reflexes. Possible causes may include carpel tunnel syndrome, meralgia paresthetica, vitamin or nutritional deficiencies, and illnesses like diabetes, syphilis, AIDS, and kidney failure. Most causes of peripheral neuropathy can be successfully treated or prevented.
Peripheral Vascular Disease
Peripheral vascular disease (PVD) refers to diseases of the blood vessels (arteries and veins) located outside the heart and brain. While there are many causes of peripheral vascular disease, doctors commonly use the term peripheral vascular disease to refer to peripheral artery disease (peripheral arterial disease, PAD), a condition that develops when the arteries that supply blood to the internal organs, arms, and legs become completely or partially blocked as a result of atherosclerosis. Peripheral artery disease symptoms include intermittent leg pain while walking, leg pain at rest, numbness in the legs or feet, and poor wound healing in the legs or feet.
Treatment for peripheral artery disease include lifestyle measures, medication, angioplasty, and surgery.
RhabdomyolysisRhabdomyolysis is a rapid deterioration and destruction of skeletal muscle. Some of the causes of rhabdomyolysis include:
- severe burns,
- muscle trauma,
- electrolyte imbalance,
- medications (statins),
- viruses, and
Take the Stroke QuizTake the Stroke Quiz to learn about stroke risks, causes, treatment, and most importantly, prevention.
Stroke Symptoms and Treatment
A stroke is an interruption of the blood supply to part of the brain caused by either a blood clot (ischemic) or bleeding (hemorrhagic). Symptoms of a stroke may include
- double vision or vision loss,
- vertigo, and
- difficulty speaking or understanding speech.
A physical exam, imaging tests, neurological exam, and blood tests may be used to diagnose a stroke. Treatment may include administration of clot-busting drugs, supportive care, and in some instances, neurosurgery. The risk of stroke can be reduced by controlling high blood pressure, high cholesterol, diabetes, and stopping smoking.
Take the Sugar QuizSugar lurks in surprising places. Take the Sugar Quiz to learn of the many ways sugar sneaks into your diet and see what you know about sugar and artificial sweeteners!