What are statins, and how do they work?
"Statins" is a class of drugs that lowers the level of low-density lipoprotein (LDL) cholesterol ("bad cholesterol") in the blood by reducing the production of cholesterol by the liver. (The other source of cholesterol in the blood is dietary cholesterol.)
How statins work
- 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.
What is cholesterol?
- 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 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 statins used for?
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
Statins' role in preventing other conditions
- 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?
Common side effects
The most common side effects are:
Serious side effects
- 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.
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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)
Other important interactions
- 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. 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).
What are the 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 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.
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Is Squid Rich in Cholesterol?
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How Dangerous Is High Cholesterol?
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High Cholesterol: Frequently Asked Questions
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What Are the Normal Cholesterol Levels By Age?
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What Are the Causes of High Cholesterol?
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- Statins May Reduce Heart Risks Linked to Sleep Apnea: Study
- Newer Blood Pressure Drugs as Good as Older Ones: Study
- Should You Be Taking Aspirin Daily?
- U.S. Task Force Backs Statins for Those 40 to 75 at Heightened Heart Risk
- People with Type 2 Diabetes May Be Overtested
- Negative News on Statins Tied to Dropped Prescriptions
- 1 in 8 American Adults Still Have High Cholesterol: CDC
- Angioplasty May Not Boost Survival for Some Heart Disease Patients
- Prescription Drug Use on the Rise in U.S.
- Statins May Dampen Protective Powers of Flu Vaccines
- No Need to Stop Taking Statins Before Surgery, Study Finds
- Heart Patients Worldwide Missing Out on Key Drugs
- Younger Women Less Likely to Take Meds After Heart Attack
- Knee, Hip Replacement Surgeries Linked to Heart Risks
- FDA Approves Second Drug in New Class of Cholesterol-Lowering Medications
- Sharp Spike Seen in Statin Use in Elderly Without Heart Disease
- Praluent Approved to Treat High Cholesterol
- FDA OKs First of New Class of Cholesterol Drugs
- Are We Taking Some Medicines for Too Long?
- Wider Use of Statin Drugs Could Save Thousands More Lives: Report
- Do Cholesterol Drugs Affect Aggression?
- Statins Might Reduce Complications After Major Lung Surgery
- Can U.S. Health-Care System Afford New, Improved Cholesterol Drugs?
- A New Way to Treat High Cholesterol?
- FDA Advisers Recommend Approval of First of 2 New Cholesterol Drugs
- Statins Pose No Greater Harm to Memory, Study Suggests
- Cholesterol Drugs May Boost Outcomes After Bypass
- Cholesterol Drugs May Lower Stroke Risk for Healthy Older Adults
- Statins May Slow Prostate Cancer Progression: Study
- Americans' Blood Triglyceride Levels Dropping: CDC
- Can Statins Help Lower Lung Cancer Death Risk?
- New Drug Class Slashes 'Bad' Cholesterol, Review Finds
- Statins Carry Some Risk for Seniors, Study Suggests
- New Guidelines Would Greatly Boost Number of Young People on Statins
- Terminally Ill Can Do Without Statins, Study Finds
- Stents Meant to Prevent Stroke May Actually Boost Risk
- Latest Diabetes Care Guidelines Focus on Individual Approach
- Experimental Drug Shows Promise in Lowering Cholesterol, Heart Attack Risk
- Statins May Help Improve Prostate Cancer Survival: Study
- Easing Depression May Boost Heart Health, Study Finds
- Statins Linked to Raised Risk of Type 2 Diabetes
- Poor Response to Statins May Mean Clogged Arteries
- 'Calculators' Doctors Use May Overestimate Heart Risks, Study Says
- Prolonged High Cholesterol in Middle Age Raises Heart Risk Later: Study
- Nearly All Diabetics Should Be on Cholesterol-Lowering Drugs: Experts
- Number of Americans Taking Statins Keeps Rising: CDC
- Daily Statin Might Raise Your Risk for Cataracts: Study
- Statins Won't Help Protect Bones, Study Finds
- Most Seniors Could Use Statins Under New Guidelines
- New Cholesterol-Lowering Drugs Show Promise
- Cholesterol Drug Vytorin Linked to Reduced Heart Attack Risk
- Experimental Cholesterol-Lowering Drug Effective, Study Reports
- Bed Position Matters for Stroke Patients, Report Shows
- Some Lung Patients Buy Cigarettes Along With Meds at Pharmacies: Study
- High Cholesterol Tied to Prostate Cancer's Return in Study
- Scientists Explain Why Statins Raise Diabetes Risk
- Cholesterol-Lowering Drugs May Help After Certain Strokes
- Heart Attack Patients Face Greater Death Risk if Any Treatment Step Missed: Study
- Older Patients More Likely to Fill Prescriptions for Generic Statins: Study
- Statins May Help Kids With Genetic Cholesterol Disorder
- Statins May Help Prevent Diabetes-Related Nerve Damage, Study Finds
- More Docs Wonder If Statins Are Worth the Risks
- Cholesterol Drugs' Benefits Far Outweigh Side Effects, Review Finds
- Statins May Aid Survival From Colon Cancer
- Cholesterol Drugs May Speed Healing After Surgery
- Is Obesity an Advantage After Heart Procedures?
- Niacin Doesn't Reduce Heart Problems, May Create Some, Research Finds
- Cholesterol Levels May Be Linked to Breast Cancer Risk
- People With Heart Disease, Diabetes May Be More Likely to Stay on Statins
- Heart Patients Without Artery Plaque Buildup Still Face Risks: Study
- Stopping Statins for Terminal Patients a Safe Option: Study
- 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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