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.
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.
Which drugs interact with statins?
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.
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.
Latest Cholesterol News
Daily Health News
Statins are a class of drugs prescribed to lower blood cholesterol. Statins also are prescribed for preventing and treating atherosclerosis. Common side effects of statins are headache, nausea, vomiting, constipation, and diarrhea. Serious side effects can occur. Review side effects, drug interactions, dosing, storage, and pregnancy safety information prior to taking this medication.
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Related Disease Conditions
Liver disease can be cause by a variety of things including infection (hepatitis), diseases, for example, gallstones, high cholesterol or triglycerides, blood flow obstruction to the liver, and toxins (medications and chemicals). Symptoms of liver disease depends upon the cause and may include nausea, vomiting, upper right abdominal pain, and jaundice. Treatment depends upon the cause of the liver disease.
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: weakness, numbness, double vision or vision loss, confusion, vertigo, 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.
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: Smoking High blood pressure High cholesterol Diabetes Family history Obesity 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.
Rhabdomyolysis is a rapid deterioration and destruction of skeletal muscle. Some of the causes of rhabdomyolysis include: severe burns, muscle trauma, coma, seizures, electrolyte imbalance, medications (statins), viruses, and bacteria. Treatment of rhabdomyolysis depends on the cause.
Angina is chest pain due to inadequate blood supply to the heart. Angina symptoms may include chest tightness, burning, squeezing, and aching. Coronary artery disease is the main cause of angina but there are other causes. Angina is diagnosed by taking the patient's medical history and performing tests such as an electrocardiogram (EKG), blood test, stress test, echocardiogram, cardiac CT scan, and heart catheterization. Treatment of angina usually includes lifestyle modification, medication, and sometimes, surgery. The risk of angina can be reduced by following a heart healthy lifestyle.
Heart Attack (Myocardial Infarction)
A heart attack happens when a blood clot completely obstructs a coronary artery supplying blood to the heart muscle. A heart attack can cause chest pain, heart failure, and electrical instability of the heart.
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.
Peripheral 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, shingles, vitamin or nutritional deficiencies, and illnesses like diabetes, syphilis, AIDS, and kidney failure. Peripheral neuropathy is diagnosed with exams and tests. Treatment for the condition depends on the cause. Usually, the prognosis for peripheral neuropathy is good if the cause can be successfully treated or prevented.
Cholesterol (Lowering Your Cholesterol)
High cholesterol and triglyceride levels increase the risk of cardiovascular disease. Getting your cholesterol and triglyceride levels in an optimal range will help protect your heart and blood vessels. Cholesterol management may include lifestyle interventions (diet and exercise) as well as medications to get your total cholesterol, LDL, HDL, and triglycerides in an optimal range.
Lower Cholesterol Levels with Diet and Medications
High-density lipoprotein (HDL) cholesterol is considered "good" cholesterol because it actually works to keep the LDL or "bad" cholesterol from building up in your arteries. Foods like extra lean meats, skim milk, and vegetable-based "butter-like" substitutes may help decrease LDL levels in the bloodstream.
Fatty Liver (NASH)
Nonalcoholic fatty liver disease or NASH 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. Treatment for fatty liver includes avoiding certain foods and alcohol. Exercise, weight loss, bariatric surgery, and liver transplantation are treatments for fatty liver disease.
Intermittent claudication, or pain and cramping in the lower leg is caused by inadequate blood flow to the leg muscles. This lack of blood flow causes a decrease in oxygen delivered to the muscles of the legs. Claudication is generally felt when walking and decreases with rest. In severe cases, claudication may be felt at rest. Narrowing of arteries cause claudication. Treatment includes exercise, medication, and in some cases surgery.
Omega-3 Fatty Acids
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Heart Attacks in Women
Heart disease, particularly coronary artery disease is the leading cause of heart attacks. Women are more likely to die from a heart attack than men. High cholesterol, high blood pressure, obesity, and high triglycerides are contributors to heart disease. Some of the common symptoms of a heart attack in women include chest pain, shortness of breath, nausea, feeling faint or woozy, and more. Heart disease can be prevented by lifestyle changes and controlling high blood pressure, cholesterol, weight, and diseases such as diabetes.
Heart Attack Treatment
A heart attack involves damage or death of part of the heart muscle due to a blood clot. The aim of heart attack treatment is to prevent or stop this damage to the heart muscle. Heart attack treatments included medications, procedures, and surgeries to protect the heart muscle against injury.
Heart Attack Pathology: Photo Essay
A heart attack is a layperson's term for a sudden blockage of a coronary artery. This photo essay includes graphics, pictures, and illustrations of diseased heart tissue and the mechanisms that lead to coronary artery disease, and possible heart attack. A coronary artery occlusion may be fatal, but most patients survive it. Death can occur when the occlusion leads to an abnormal heartbeat (severe arrhythmia) or death of heart muscle (extensive myocardial infarction).
Heart Disease in Women
Heart disease in women has somewhat different symptoms, risk factors, and treatment compared to heart disease in men. Many women and health professionals are not aware of the risk factors for heart disease in women and may delay diagnosis and treatment. Lifestyle factors such as diet, exercise, tobacco use, overweight/obesity, stress, alcohol consumption, and depression influence heart disease risk in women. High blood pressure, high cholesterol, and diabetes also increase women's risk of heart disease. Electrocardiogram (EKG or ECG), stress-ECG, endothelial testing, ankle-brachial index (ABI), echocardiogram, nuclear imaging, electron beam CT, and lab tests to assess blood lipids and biomarkers of inflammation are used to diagnose heart disease. Early diagnosis and treatment of heart disease in women saves lives. Heart disease can be prevented and reversed with lifestyle changes.
High Cholesterol: Frequently Asked Questions
Cholesterol occurs naturally in the body. High blood cholesterol levels increase a person's risk of developing heart disease, heart attacks, strokes, TIAs, and more. In addition to medication (fibrates, statins, bile acid sequestrants, and niacin), lifestyle changes can be made to lower blood cholesterol levels
Heart Attack Prevention
Heart disease and heart attacks can be prevented by leading a healthy lifestyle with diet, exercise, and stress management. Symptoms of heart attack in men and women include chest discomfort and pain in the shoulder, neck, jaw, stomach, or back.
Heart Disease Treatment in Women
Heart disease treatment in women should take into account female-specific guidelines that were developed by the American Heart Association. Risk factors and symptoms of heart disease in women differ from those in men. Treatment may include lifestyle modification (diet, exercise, weight management, smoking cessation, stress reduction), medications, percutaneous intervention procedure (PCI), and coronary artery bypass grafting (CABG). Heart disease is reversible with treatment.
Stroke is the third leading killer in the United States. Some of the warning signs of stroke include sudden confusion, trouble seeing with one or both eyes, dizziness, loss of balance, and more. Stroke prevention and reatable risk factors for stroke include lowering high blood pressure, quit smoking, heart disease, diabetes control and prevention.
Treatment & Diagnosis
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- More Americans Working to Control Blood Pressure, Cholesterol: CDC
- New Drug May Help Lower 'Bad' Cholesterol Beyond Statins
- Prescription Drug Use Continues to Climb in U.S.
- Statin Users Eating More Bad Food Than a Decade Ago, Study Shows
- Cholesterol-Lowering Drugs May Boost a Man's Sex Life: Study
- New Drug Lowers Cholesterol Beyond What Statins Can Do, Study Finds
- Many Kids May Have High Cholesterol, Regardless of Weight
- Almost 13 Million More Americans Could Take Statins Under New Guidelines
- Low-Dose Statins Good Option for Some Heart Patients: Study
- Minority Patients Less Likely to Stick With Heart Attack Meds: Study
- Design Flaws Plague Many Animal-Based Drug Studies, Researchers Say
- Statin Therapy May Prevent Delirium in Critically Ill Patients
- New Blood Pressure Guidelines Raise the Bar for Taking Medications
- Some Doctors Challenge New Statin Guidelines
- Could Vaccines Someday Improve Heart Health?
- Statins Not Linked to Memory Loss, Dementia, Review Suggests
- New Cholesterol Drug Guidelines: Q&A
- Heart Experts Warn Against 'Crash' Diets
- New Guidelines May Widen Use of Statins
- Can 'Good' Cholesterol Protect Against MS?
- Urine Test May Spot Heart, Kidney Risk in Kids With Type 1 Diabetes
- Metformin Won't Help Heart Patients Without Diabetes: Study
- Statin Use Linked to Lower Prostate Cancer Death Risk
- Some Improvement Seen in U.S. Cholesterol Levels: CDC
- Efforts to Improve Intensive-Care Outcomes Produce Mixed Results
- Cholesterol Drugs May Boost Your Gums' Health, Too
- New Cholesterol-Lowering Drug Shows Early Promise
- Statins May Not Harm Memory, Thinking After All
- Statins Linked to Raised Risk of Cataracts in Study
- Should Everyone Over 65 Take a Statin?
- High Cholesterol May Be Particularly Bad for Middle-Aged Men
- Statin Use May Reduce Parkinson's Risk, Study Says
- Drug for Pulmonary Hypertension Shows 'Modest' Benefit in Studies
- Most Statin Users Won't Have Major Side Effects
- Stronger Statins Don't Up Kidney Injury Risk, Study Finds
- Statins Plus Certain Antibiotics May Set Off Toxic Reaction: Study
- Pace of New Drug Advances May Be Slowing, Study Finds
- Cholesterol Drugs Linked to Muscle, Joint Problems: Study
- Statins May Hamper Workout Results
- Could Statins Raise Diabetes Risk?
- Cholesterol Drugs Might Boost Kidney Cancer Survival
- Statin Side Effects Often Manageable: Study
- Modest Cardiac Benefit From Chelation Therapy Not Enough to OK Use: Experts
- High-Dose Statins Linked to Acute Kidney Damage
- Niacin Won't Help, May Harm Heart Patients: Study
- Drug May Ease Angina in People With Type 2 Diabetes
- Study: Mega Vitamins Won't Help After Heart Attack, Chelation Treatment Might
- TV Ads for Statins May Drive Overtreatment
- Niacin-Statin Combo May Cause Side Effects for Heart Patients
- Healthy Diet May Prevent Additional Heart Trouble
- Statins Plus Exercise Best at Lowering Cholesterol, Study Finds
- New Drug to Lower 'Bad' Cholesterol Shows Promise
- Transcendental Meditation May Lower Heart Risk
- Statins Linked to Reduced Cancer Death
- New Drug May Help Those Who Can't Take Statins
- Many Older Heart Attack Survivors Don't Stick With Meds
- Cholesterol Levels Down Among U.S. Adults
- Statins Tied to Reduced Glaucoma Risk
- Many Heart Attacks May Go Unrecognized in Seniors
- Statin Use Tied to Possible Boost in Cataract Risk
- Statins Won't Hurt, Might Even Help, Your Pancreas: Study
- Statin Diabetes Risk Limited to Those at High Risk
- Fish Oil Doesn't Lower Heart Risk in Diabetics
- The Health Benefits, and Risks, of Alcohol
- Statins May Work Better in Men Than in Women
- Fish Oil Won't Save Diabetics' Hearts, Research Suggests
- Study: Statins May Be Linked to Fatigue
- Daily Low-Dose Aspirin Risks Seem to Outweigh Gains for Many: Study
- Some Cholesterol Drugs May Slow Prostate Growth
- Benefits of Widespread Statin Use Outweigh Risks: Study
- Statins May Help Prevent Irregular Heartbeat in Elderly
- Rate of Statin-Linked Muscle Woes Unclear, Study Suggests
- Cholesterol Levels in the U.S. on the Decline
- Role of Screening, Monitoring in Early Kidney Disease Unclear
- Rheumatoid Arthritis Patients Who Quit Statins May Face Raised Death Risk
- New Injection Might Lower Tough-to-Treat Cholesterol
- Biologic Drug Lowers LDL Cholesterol
- Showing Patients Images of Their Clogged Arteries a Powerful Wake-Up Call
- Low 'Bad' Cholesterol Levels May Be Linked to Cancer Risk
- Statin Alternative Looks Promising in Early Trials
- Test May Spot Heart Attacks Before They Happen
- Could Statins Help Prevent Pneumonia?
- Depression Tied to Earlier Death in Heart Patients
- Can Statins Prevent Parkinson's Disease?
- Statin Risks Outweighed by Statin Benefits
- Could a Statin Lower Your Risk for Depression?
- New Warnings on Cholesterol-Lowering Statins
- Heart Disease May Be Risk Factor for Prostate Cancer
- It's 'Buyer Beware' When Getting Statins Off the Internet
- Statins Equally Effective in Women and Men
- Statins May Stave Off Liver Cancer in People With Hepatitis B
- Statins May Raise Diabetes Risk in Older Women
- Cholesterol-Lowering Drugs Tied to Flu Survival
- Generic Lipitor FAQ
- Heart Attack Complications More Likely for Women Smokers
- Raising 'Good' Cholesterol May Cut Heart Risk in Diabetes Patients
- FDA Limits Highest Dose of Cholesterol Drug Statin (Includes Zocor, Vytorin, Simcor)
- Trial Stopped After Niacin Brings No Benefit to Heart Patients
- Many Heart Patients Aren't Taking Needed Drugs
- 'Mini-Strokes' May Increase Risk of Heart Attack
- Osteoporosis Drugs Linked to Lower Cancer Risk
- Where Do the Most Active People Live?
- New Debate on C-Reactive Protein Test and Statins
- Cholesterol-Lowering Drugs May Cut RA Risk
- Cholesterol Study: Low HDL May Not Be So Bad
- Stroke Patients Discharged Without Statins
- Statins May Lower Testosterone, Libido
- Should Healthy People Take Statins?
- FDA Warns of Zocor Risk to Muscles
- Statins May Be Linked to Diabetes Risk
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