Statins: Marvelous medications for cholesterol

For a young physician just starting on his medical practice today, life before the statins must seem like the dark ages of medicine. Indeed, these powerful medications have revolutionized medical care and improved the outlook for millions of people with heart disease or cardiovascular risk factors.

It’s hard to imagine that all this progress has occurred in the short span since 1987, when the first statin drug was introduced. And despite all the scientific attention that has been lavished on these medications, doctors are still learning more about the ways they can help.

What Are The Statins?

All six currently available drugs (see table) act in the same way: They inhibit the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a liver enzyme that’s better known by its short name, HMG-CoA reductase. It’s the key enzyme responsible for cholesterol production. When it is blocked, less cholesterol is produced and blood cholesterol level falls. But the drugs have another benefit: As cholesterol production falls, the liver takes up more cholesterol from the blood, so blood levels fall 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 percent of a dose getting into the bloodstream; for lovastatin, the least well-absorbed, the figure is 30 percent. 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 one to three 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 evenings so that the 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 has been reported to produce higher blood levels in Asians than in other individuals. Asians, therefore, have been advised to use the drug with caution and generally not to exceed 20mg a day, half the maximum dose for non-Asians. A recent study reported in Malaysia, however, disputes this. The IPEP trial involving 1,417 patients in 215 centers showed that rosuvastatin was well-tolerated and safe among its Malaysian subjects.

Interactions

In our medicated society, many patients who need a statin also take other medications. 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 can help you sort this out – or you can take pravasatin, which is metabolized differently and has 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 four to six weeks to achieve their maximum effect. In general, doctors should wait about two months before they adjust a statin dose or add another medication.

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 statin drugs is very effective at boosting levels of HDL ("good") cholesterol; the average is only five to 15 percent.

Triglycerides are another matter; atorvastatin and rosurvastatin are the only members of the groups that reduce triglyceride levels, by 30 percent or more. Even though doctors are not sure if lowering triglycerides will help prevent heart decease, 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 one or two percent 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 irreversible.

Clinical Experience

By now, the first five statins have been used so widely that doctors are equally confident about each one’s efficacy and safety. Because rosuvastatin is much newer, there is less information about its safety and ability to reduce cardiac events, but it is very effective at lowering LDL cholesterol levels.

New research suggests that statins may have benefits beyond lowering cholesterol, perhaps fighting vascular inflammation and improving bone mineral density. Doctors are not sure if any of the statins will actually prove effective in these areas, and they still don’t know which member of the group will have the best non-cardiac effects.

The Bottom Line

Cost is by far the most common reason patients are not prescribed the drug or are switched from one statin to another. It makes good sense though to pick the least expensive drug that will do the job right.

But above all, remember that diet, exercise, and weight control are always the first step in preventing atherosclerosis. Like the statins, they lower cholesterol, and like the statins, they have many benefits beyond cholesterol. Even in the most optimistic trials, statin therapy reduces risk by no more than 40 percent, leaving plenty of room for diet and exercise to do their work, even when these marvelous drugs are on board.