Not everyone responds to the same degree to the effects of a heart-healthy diet. Despite their benefits, these lifestyle measures don’t always lower LDL (”bad”) cholesterol sufficiently to significantly reduce the risk of a heart attack. When that is the case, cholesterol medicine is often recommended as well.

Many different cholesterol medicines have been developed in recent years. How cholesterol medicines works? Some reduce the amount of cholesterol the liver makes while others reduce the amount of dietary cholesterol that is absorbed from food.

The benefits of reducing total blood cholesterol and LDL cholesterol with cholesterol medicine have been clearly demonstrated by a number of well-designed studies. About 90% of the cholesterol-lowering medicines taken by Americans are in a class of medications known as statins. These cholesterol medicines lower cholesterol by at least 20% through the same basic action: They inhibit HMG-CoA reductase, a key enzyme that controls how much cholesterol is produced in the liver. The result is lower blood levels of LDL cholesterol. Statins also lower elevated triglycerides and raise HDL (“good”) cholesterol. Statins also reduce inflammation in arterial walls; relax blood vessels; improve blood flow to the heart; inhibit clotting; and stabilize and reduce the size of the fatty plaques that form in the walls of arteries. More research is needed to determine the clinical significance of these effects.

If you are one of the millions currently taking a statin drug or are a candidate for starting on one, you are probably aware that there is more than one statin. The first statin, lovastatin (brand name: Mevacor), was introduced 17 years ago, and a total of six such drugs are now on the market. The others include atorvastatin (Lipitor), fluvastatin (Lescol), pravastatin (Pravachol), simvastatin (Zocor), and rosuvastatin (Crestor), which is the most recent one (it was approved in August, 2003). Three statins - lovastatin, pravastatin, and simvastatin - are available in generic form. Some of the statins are now available in combination with other lipid-lowering drugs, and one of them (atorvastatin) is sold in combination with a blood pressure lowering drug (in a pill called Caduet). As the number of statins has increased, so have the efforts by drug companies to promote the advantages of their particular product. But is one statin “the best” - or are some statins better than others? Are there any side effects taking cholesterol medicine? Why should you be on atorvastatin when your friend is on pravastatin or simvastatin? What factors did your doctor consider in prescribing a specific statin for you? And should your preferences be taken into account?

Direct comparisons of the potency of the various statin formulations are limited. The Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin (STELLAR) trial, reported in 2003 in the American Journal of Cardiology, is the largest comparison to date. A randomized, controlled trial that involved more than 2,400 people, STELLAR compared the three most widely prescribed statins - atorvastatin, simvastatin, and pravastatin - with the newest, rosuvastatin, across a range of doses. After 6 weeks of treatment, rosuvastatin lowered LDL cholesterol by 46% to 55%, compared with 37% to 51% for atorvastatin, 28% to 46% for simvastatin, and 20% to 30% for pravastatin. Not surprisingly, more people taking rosuvastatin achieved their LDL cholesterol goals. Rosuvastatin and atorvastatin also lowered triglycerides by 20% to 28%, significantly more than pravastatin (8% to 13%) or simvastatin (12% to 18%). In addition, across dosage ranges, rosuvastatin produced a slightly greater rise in HDL cholesterol levels than the other statins - although the clinical benefit of such an increase is unknown.

In addition to potency, several other medical and nonmedical factors may influence you and your doctor’s choice of a statin. They include:

Cost. Statins vary widely in price. For example, the cost for 30 tablets of the 20-mg dose size ranges from about $25 for generic lovastatin to about $135 for brand-name simvastatin (Zocor).

When to take. All of the statins, except atorvastatin and rosuvastatin, should be taken in the evening or at bedtime to achieve their maximal effect (because cholesterol production is highest at night). Atorvastatin and rosuvastatin have a relatively long duration of action and may be taken any time during the day. Lovastatin should be taken with meals to increase absorption.

Drug interactions. Atorvastatin, simvastatin, and lovastatin may interact with certain drugs because they are metabolized by the same enzyme system in the liver (see chart). Pravastatin, rosuvastatin, and fluvastatin are metabolized differently and appear less prone to such interactions. However, safety data on rosuvastatin are more limited because the drug is so new.

Side effects. Myopathy, or muscle pain and weakness, is the most common side effect of all the statins. More dangerous is myositis, a severe muscle inflammation that can progress to rhabdomyolysis, a potentially fatal condition that can damage the kidneys. Rhabdomyolysis is rare when currently available statins are taken alone, but it can occur when they are combined with the triglyceride-lowering fibrates gemfibrozil (Lopid) or fenofibrate (Tricor, Lofibra). Fibrates, particularly gemfibrozil, may raise the concentration of statins and increase their potential for causing muscle inflammation.

An uncommon adverse effect of all statins is an increase in liver enzymes. As a precaution, people taking these drugs should have periodic blood tests (e.g., every 4 to 6 months) to monitor liver function. Any elevation in liver enzymes rapidly reverses when the statin is discontinued. No instances of permanent liver damage have been reported.

A statin’s ability to lower LDL cholesterol is the most important factor to consider when choosing a statin. If your initial cholesterol level is only mildly elevated, your doctor may opt for any of the statins. On the other hand, if you are at elevated risk for heart disease, your initial cholesterol level is very high and your triglyceride levels are also high, or you’ve failed to respond adequately to one of the other statins, a more potent formulation - like atorvastatin, rosuvastatin, or simvastatin - may be more appropriate. Once medical issues are addressed, other factors, such as cost and the time of day you prefer to take your medication, can be considered. No matter which drug is chosen, the standard approach is to start at a low dose and increase the dosage if a greater drop in LDL cholesterol levels is needed. (If you take a statin drug, you should be monitored by your doctor to be sure the cholesterol medicine is lowering your LDL cholesterol sufficiently and also for any side effects, especially liver toxicity and muscle inflammation, which are rare).