Understanding Cholesterol-Lowering Medications

Cholesterol is a waxy, fatlike substance that your body needs to function normally. Cholesterol is naturally present in cell walls or membranes everywhere in the body, including the brain, nerves, muscles, skin, liver, intestines, and heart.

Your body uses cholesterol to produce many hormones, vitamin D, and the bile acids that help digest fat. The cholesterol in your blood comes from 2 sources: the foods you eat and your liver. However, your liver makes enough cholesterol to satisfy your body’s needs. It takes only a small amount of cholesterol in the blood to meet these needs. If you have too much cholesterol in your bloodstream, the excess may be deposited in arteries, including the coronary (heart) arteries, where it contributes to the narrowing and blockages that cause the signs and symptoms of heart disease.

What causes high cholesterol?

Several drugs and diseases can bring about high cholesterol, but for most people, a high-fat diet, obesity, a sedentary lifestyle, smoking, excessive alcohol consumption, or inherited risk factors are the main causes.

Risks of high cholesterol

If you have too much cholesterol in your bloodstream, the excess may be deposited in arteries, which leads to atherosclerosis (commonly called hardening of the arteries). Atherosclerosis may contribute to high blood pressure, heart attack, stroke, blood clots, or impotence.

If you have high cholesterol, your doctor will recommend the following lifestyle changes to help you lower your cholesterol levels.

• Low-saturated fat, low-cholesterol diet
  
  
• Increased physical activity
  
  
• Smoking cessation
  
  
• Weight loss

If these lifestyle changes do not lower your risk for developing coronary heart disease after about 3 months, your doctor may consider prescribing a cholesterol-lowering medication. These medications include statins, bile acid sequestrants, cholesterol absorption inhibitors, nicotinic acid agents, and fibrates. If your doctor prescribes one of these medications, you must still follow your cholesterol-lowering diet, be more physically active, lose weight if you are overweight, and control or stop all of your other heart disease risk factors (including high blood pressure, diabetes, and smoking).

Taking all these steps together may lessen the amount of medication you need or make the medication work better, which reduces your risks associated with high cholesterol.

Atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor, Altocor), pravastatin (Pravachol), simvastatin (Zocor), and rosuvastatin (Crestor) are commonly prescribed statins (cholesterol-lowering drugs).

• How do statins work? Statins inhibit the enzyme HMG-CoA reductase, which controls the rate of cholesterol production in the body. These drugs lower cholesterol 20-60% by slowing the production of cholesterol and by increasing the liver's ability to remove the “bad” cholesterol (low-density lipoprotein or LDL) already in the blood. Statins lower LDL cholesterol levels more effectively than other types of drugs. They also modestly increase “good” cholesterol (high-density lipoprotein or HDL) and decrease total cholesterol and triglycerides. Results are usually seen after 4-6 weeks of taking statins. Statins have been studied extensively and overall have been proven to decrease the risk of heart attack, stroke, and other coronary artery diseases that are related to high cholesterol levels.



• Who should not use these medications? You should not use statins if you fit any of the following situations:
  
  
  • You are allergic to statins or their ingredients.
  
  
  
  • You are pregnant or are planning a pregnancy.
  
  
  
  • You are breastfeeding.
  
  
  
  • You have active liver disease.
  
  
  
  • You excessively consume alcohol.
  
  
  
  • You have a history of myopathy (a type of muscle disease).
  
  
  
  • You have renal failure due to rhabdomyolysis.


• Use: Statins come in tablet or capsule forms and are usually taken with the evening meal or at bedtime.



• Children: Some statins are also indicated for children aged 10-17 years with heterozygous familial hypercholesterolemia (girls in this age range must have already begun menstruating). When used along with diet, statins reduce total cholesterol, LDL, and apo B levels in children with heterozygous familial hypercholesterolemia. After an adequate trial of diet therapy, statins may be considered for treatment in children if the following findings are present:



• • LDL-C remains greater than or equal to 190 mg/dL.
  
  
  
  • LDL-C remains greater than or equal to 160 mg/dL and one of the following exists:
  
  
  
  • • A positive family history of premature cardiovascular disease
    
    
    
    • Two or more other cardiovascular disease risk factors in the pediatric patient


• Drug or food interactions: Consuming large quantities of grapefruit juice, more than 1 quart per day, decreases the ability of the liver to metabolize some statins, such as atorvastatin, simvastatin, or lovastatin. Also, and possibly more importantly, statins and certain other medications can interact, causing serious side effects. Tell the doctor about any prescription and nonprescription medications you are taking, including the following:
  
  
  • Vitamins
  
  
  
  • Herbal supplements
  
  
  
  • Medication for your immune system, such as drugs prescribed following organ ransplantation
  
  
  
  • Other cholesterol medications, such as fibrates or nicotinic acid
  
  
  
  • Medication for infections, such as erythromycin, clarithromycin, itraconazole, or ketoconazole
  
  
  
  • Birth control pills
  
  
  
  • Medication for heart failure
  
  
  
  • Medication for HIV or AIDS
  
  
  
  • Warfarin (Coumadin) (Warfarin may have an increased effect when administered with some statins, such as rosuvastatin or simvastatin. The international normalized ratio [INR] must be closely monitored when warfarin is administered with statins.)


• Side Effects: Statins are well tolerated, and serious side effects are rare.
  
  
  • If you experience diffuse muscle soreness, pain, and weakness; vomiting; or stomach pain or if your urine is brown (a possible sign of muscle breakdown), contact your doctor immediately and stop taking the statin medication. You may need blood tests for possible muscle problems. Rarely, widespread muscle breakdown, known as rhabdomyolysis, can occur, usually in people who are taking other drugs that interfere with the breakdown of the statin and in people with advanced kidney problems. This is a medical emergency.
  
  
  
  • Some people experience an upset stomach, gas, constipation, and abdominal pain or cramps. These symptoms are usually mild to moderate and generally disappear as the body adjusts. Liver function is usually monitored in patients taking statins. Rare reports of neuropathy (numbness and tingling) affecting the hands, arms, feet, and legs have been described.

Cholestyramine (Questran, Questran Light, Prevalite, LoCholest), colestipol (Colestid), and colesevelam (WelChol) are commonly prescribed bile acid sequestrants.

• How do bile acid sequestrants work? These drugs bind with cholesterol-containing bile acids in the intestines and are then eliminated in the stool. The usual effect of bile acid sequestrants is to lower LDL cholesterol by about 10-20%. Small doses of sequestrants can produce useful reductions in LDL cholesterol. Bile acid sequestrants are sometimes prescribed with a statin to enhance cholesterol reduction. When these drugs are combined, their effects are added together to lower LDL cholesterol by more than 40%. These drugs are not effective for lowering triglycerides.
  
  
• Who should not use these medications? Individuals who are allergic to bile acid sequestrants or who have a medical history of bile obstruction should not use these agents. Patients with phenylketonuria should not take aspartame-containing bile acid sequestrants such as Questran Light.
  
  
• Use: Bile acid sequestrant powders must be mixed with water or fruit juice and are typically taken once or twice (rarely, 3 times) daily with meals. Tablets must be taken with large amounts of fluids to avoid stomach and intestinal problems.
  
  
• Drug or food interactions: Bile acid sequestrants decrease the ability of the body to absorb numerous drugs such as warfarin, thyroid hormone, amiodarone, sulindac, methotrexate, digoxin, glipizide, phenytoin, imipramine, niacin, methyldopa, tetracycline, clofibrate, hydrocortisone, ezetimibe, or penicillin. They also inhibit fat-soluble vitamins (vitamin A and E); thus, patients taking these agents for a long time may need vitamin supplementation. Take bile acid sequestrants 2 hours before or after antacids, since antacids may decrease their effectiveness. Talk to your doctor or pharmacist for the best time to take your medications.

• Side effects: Bile acid sequestrants are not absorbed from the gastrointestinal tract, and 30 years of experience with these drugs indicates that long-term use is safe. These agents may cause constipation, bloating, nausea, or gas.

Ezetimibe (Zetia) is a commonly prescribed cholesterol absorption inhibitor.

• How do cholesterol absorption inhibitors work? This new drug class was approved by the US Food and Drug Administration (FDA) in late 2002. Ezetimibe by itself reduces LDL cholesterol by 18-20% by selectively decreasing cholesterol absorption, and other drugs within this class are also effective in mildly lowering triglycerides. They are probably the most useful in people who cannot take statins or as an additional drug for people who take statins but notice side effects when the statin dose is increased. Adding ezetimibe to a statin increases the cholesterol-lowering effect by a 2- to 3-fold factor.
  
  
• Who should not use these medications? Individuals who are allergic to cholesterol absorption inhibitors should not take them.
  
  
• Use: These drugs are taken as a tablet once daily, with or without food. They are often combined with statins to increase effectiveness.
  
  
• Drug or food interactions: Take cholesterol absorption inhibitors at least 2 hours before or 4 hours after bile acid sequestrants. Fenofibrate, gemfibrozil, and cyclosporine increase the blood levels of ezetimibe.

• Side effects: Study findings indicate that the incidence of side effects in people taking ezetimibe is similar to that of people taking sugar pills. If administered with a statin, the cautions for statins should be observed.

Niacin, Niacor, and Slo-Niacin are commonly prescribed nicotinic acid agents.

• How do nicotinic acid agents work? Nicotinic acid (also called niacin), a water-soluble B vitamin, improves blood levels of all lipoproteins when given in doses well above the vitamin requirement. Nicotinic acid lowers total cholesterol, LDL cholesterol, and triglyceride levels, while raising HDL cholesterol levels. Nicotinic acid reduces LDL cholesterol levels by 10-20%, reduces triglycerides by 20-50%, and raises HDL cholesterol by 15-35%. Nicotinamide is a niacin by-product after it is broken down by the body. Nicotinamide does not lower cholesterol levels and should not be used in place of nicotinic acid.
  
  
• Who should not use these medications? Individuals who are allergic to nicotinic acid, and those who have liver disease, active peptic ulcer, or arterial bleeding, should not use nicotinic acid agents.
  
  
• Use: When niacin is started, the dose should be gradually increased to minimize side effects until the effective cholesterol-lowering dose is reached.
  
  
  • There are 2 types of nicotinic acid: immediate release and extended release. The immediate-release form of niacin is inexpensive and widely available without a prescription, but because of the potential side effects, it must not be used for cholesterol lowering without the monitoring of a doctor.
    
    
  • Extended-release niacin is often better tolerated than crystalline niacin. However, its potential to cause liver damage is probably greater. Therefore, the dose of extended-release niacin is usually limited to 2 grams per day.
    
    
• Drug or food interactions: The effect of high blood pressure medicines may also be increased while you are on niacin. If you are taking high blood pressure medication, it is important to set up a blood pressure monitoring system while you are getting used to your new niacin regimen.
  
  
• Side effects: A common and troublesome side effect of nicotinic acid is flushing or hot flashes, which are the result of blood vessels opening wide. Most people develop a tolerance to flushing, which can sometimes be decreased by taking the drug during or after meals or by the use of aspirin or other similar medications prescribed by your doctor 30 minutes prior to taking niacin. The extended-release form may cause less flushing than the other forms. A variety of gastrointestinal symptoms, including nausea, indigestion, gas, vomiting, diarrhea, and the activation of peptic ulcers, has been seen with the use of nicotinic acid. Three other major adverse effects include liver problems, gout, and high blood sugar. Risk of the latter 3 complications increases as the dose of nicotinic acid is increased. Because of the effect on your blood sugar level, your doctor may not prescribe this medicine for you if you have diabetes.

Gemfibrozil (Lopid) and fenofibrate (Tricor) are commonly prescribed fibrates.

• How do fibrates work? Fibrates are primarily effective in lowering triglycerides and, to a lesser extent, in increasing HDL cholesterol levels.
  
  
• Who should not use these medications? Individuals who are allergic to fibrates, or who have liver disease (including biliary cirrhosis or gallbladder disease) or severe kidney disease, should not take these agents.
  
  
• Use: Fibrates are typically ingested with the morning and/or evening meals.
  
  
• Drug or food interactions: When combined with statins, an increased risk of myopathy or rhabdomyolysis may occur. Fibrates increase the effect of warfarin and oral diabetic drugs (such as glyburide); therefore, closer monitoring of your bleeding time and blood sugar will be required. Patients taking cyclosporine may have decreased levels (your doctor will monitor you and determine if a dose adjustment is needed).
  
  
• Side effects: Fibrates may cause stomach or intestinal discomfort and may increase the likelihood of developing gallstones. Rarely, kidney function may decrease.
  
  

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American Heart Association, Cholesterol

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Author: Mary L Windle, Pharm D, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, .com, Inc.

Editors: Alan D Forker, MD, Program Director of Cardiovascular Fellowship, Professor of Medicine, Department of Internal Medicine, University of Missouri at Kansas City School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, ; Michael E Zevitz, MD, Clinical Assistant Professor, Department of Medicine, Rosalind Franklin University of Medicine and Science, Chicago.