NOVEMBER / DECEMBER 2004

AROUND HARVARD

This article originally appeared in the November 2004 Harvard Men’s Health Letter and is provided courtesy of Harvard Health Publications.

Medications for cholesterol: Which statin is best?

Until 1987, doctors had a hard time helping patients reduce high blood cholesterol levels. Diet, exercise, and weight control were the main techniques available. These therapies do work, and they remain the key to prevention today, but many patients don’t comply fully and many don’t respond completely. Cholesterol-lowering medications have been available for decades, but most were unpleasant to take or toxic, and few were dramatically effective. All that changed when lovastatin (Mevacor) burst on the scene. A runaway success, it rapidly became the drug of choice for most patients with high cholesterol.

Within 10 years, lovastatin was joined by five other drugs in the statin family (see Table 1). The drugs are similar, and doctors used them interchangeably until 2001, when cerivastatin (Baycol) was abruptly taken off the market because it was linked to 31 deaths from severe muscle damage (rhabdomyolysis). The other statin drugs have been carefully scrutinized, and they still appear safe and effective. But the cerivastatin tragedy is a reminder that there are differences among these drugs. If you need a statin, which is the best choice?

How statins work
Members of the statin family have more similarities than differences. All work in the same way: They inhibit the activity of 3-hydroxy-3-methylglutaryl-coenyzme A reductase. It’s the chief enzyme for cholesterol production; when it’s blocked, the liver manufactures less cholesterol and blood cholesterol levels fall. And statins share another important benefit: As cholesterol production falls, the liver takes up more cholesterol from the blood, so levels drop even further.

Pharmacology
There are some differences in how the body absorbs, distributes, and eliminates the statin drugs. Most of the distinctions are technical, but some can be important for certain patients.

• Origins. Lovastatin, pravastatin, and simvastatin are natural compounds, while fluvastatin, atorvastatin, and rosuvastatin are synthetic.

• Absorption. Although all the statins are absorbed well, fluvastatin enters the body best, with 98% of a dose getting into the bloodstream; for lovastatin, the least well absorbed, the figure is 30%. The percentages may matter only to scientists, but the effect of food will matter to you. Because lovastatin is better absorbed with food, it should be taken with meals. Pravastatin, however, is best absorbed if it’s taken on an empty stomach. Food does not appear to affect the other statins to a significant extent.

• Distribution. All the drugs are able to enter the liver, which is where they do their work. Three of the statins dissolve in fat, three in water. While it’s a technical distinction, it may have a practical aspect. Since only the fat-soluble statins — lovastatin, simvastatin, and atorvastatin —can enter the brain, patients who experience insomnia or other central nervous system side effects of one of these statins may have better luck with pravastatin, fluvastatin, or rosuvastatin, which do not cross into the brain.

• Elimination. It takes about 19 hours for the body to clear half a dose of rosuvastatin and 14 hours for atorvastatin; for the other drugs, it’s just 1–3 hours. The difference is important. Atorvastatin and rosuvastatin can be taken at any time of day, but the other statins should be taken in the evening so that levels in the liver are high in the dead of night, when the body produces most of its cholesterol.

All the statin drugs are eliminated by the liver and kidneys, but the proportions vary. Pravastatin depends on the kidneys more than the others, so patients with even moderate kidney disease should take reduced doses; patients with advanced kidney disease may need to lower their doses of lovastatin, simvastatin, or rosuvastatin.

Rosuvastatin produces higher blood levels in Asians than in other individuals. Asians should use the drug with caution and should probably not exceed 20 mg a day, half the maximum dose for non-Asians.

Interactions
In our medicated society, many patients who need a statin take other medications as well. Statins can interact with a wide range of drugs; various antibiotics and anti-seizure medications head the list. Depending on the drugs involved, blood levels of the statin or the other medications may be abnormally high or low. Your doctors and pharmacists can help you sort this out — or you can take pravastatin, which is metabolized differently and has far fewer drug interactions.

Grapefruit juice is not a drug, but it can boost the blood levels of many medications, including all the statins except pravastatin and rosuvastatin.

Potency
It’s the biggest difference among the statin drugs, and can require a surprising change in dosage when patients are switched from one statin drug to another (see Table 2).

All the statins take 4–6 weeks to achieve their maximum effect. In general, doctors should wait about two months before they adjust a statin dose or add other medications.

Triglycerides and HDL
Although their potency varies, all of the statins can do a good job of lowering the LDL (“bad”) cholesterol; it’s how they reduce the risk of heart attacks, cardiac deaths, and some types of strokes. Unfortunately, none of the drugs is very effective at boosting levels of HDL (“good”) cholesterol; the average is 5%–15%.

Triglycerides are another matter. Atorvastatin and rosuvastatin are the only members of the group that reduce triglyceride levels, by 30% or more. Even though doctors are not sure if lowering triglycerides will help prevent heart disease, these two statins are the best for patients with high triglycerides.

Side effects
With the exception of the now withdrawn cerivastatin, all the statins have similar side effects, and all are quite safe. The most important adverse reactions are liver inflammation and muscle damage. Doctors can use blood tests to check for both problems. Patients who experience fatigue, loss of appetite, nausea, abdominal distress, or muscle aches, fatigue, or cramps should stop taking their statin and get blood tests promptly. Fortunately, both side effects are uncommon, affecting only 1% or 2% of patients, and they almost always resolve quickly when the medication is stopped. Other even less common side effects include lack of concentration, insomnia or vivid dreams, rash, and nerve damage. Some men may develop breast enlargement or erectile dysfunction; like the other adverse reactions, though, they are reversible.

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