11 - statins

Statins are among the most commonly prescribed drugs in medicine. Clinical studies have shown that statins significantly reduce the risk of heart attack and death in patients with proven coronary artery disease (CAD), and can also reduce cardiac events in patients with high cholesterol levels who are at increased risk for heart disease. While best known as drugs that lower cholesterol, statins have several other beneficial effects that may also improve cardiac risk, and that may turn out to be even more important than their cholesterol-reducing properties.

The Statin Drugs

• Lipitor (atorvastatin)
• Lescol (fluvastatin)
• Mevacor (lovastatin)
• Pravachol (pravastatin)
• Zocor (simvastatin)
• Crestor (rosuvastatin)

Lovastatin and simvastatin are also available as generic drugs. A seventh statin, Baycol (cerivastatin), was removed from the market in 2001 because of potentially serious side effects.

What are the benefits of statins?

Most people think of statins primarily as cholesterol-lowering drugs. Statins improve blood cholesterol levels primarily by inhibiting a liver enzyme called HMG Co-A reductase, thus reducing the liver's ability to make cholesterol. Statins cause a significant reduction in LDL "bad" cholesterol levels, a moderate reduction in triglyceride levels, and a small increase in levels of HDL cholesterol ("good" cholesterol).

In addition to lowering cholesterol, however, statins have several other effects that are helpful in patients known or likely to have CAD. These beneficial effects include:

• Reducing the size of plaques in the arteries.
• Stabilizing plaques, so they are less likely to rupture (and therefore less likely to cause acute heart attacks).
• Reducing inflammation (which is now thought to be an important component of plaque formation and rupture).
• Reducing CRP levels
• Decreasing blood clot formation (Blood clot formation at the site of plaque rupture is the cause of most heart attacks).
• Improving overall vascular function

In addition, studies have reported other possible benefits from statins, including a reduced incidence of Alzheimer's disease, particular benefits in diabetics, prevention of cataracts, and reducing blood pressure.

What are the side effects of statins?

The most common side effects of the statins are gastrointestinal -- nausea, gas, upset stomach. Less common are headache, dizziness, rash, and sleep disturbances.

Statins also cause elevations in liver enzymes in about 1 in 100 patients. While blood tests should be checked after a few weeks of treatment, there is little evidence that statins ever cause serious or permanent liver damage.

Statins cause a muscle disorder producing muscle weakness, and occasionally pain, in about 1 in 1,000 patients. In the large majority of cases, the symptoms resolve if the statin is stopped, or if the dose is reduced. Rarely, sufficient muscle damage can result in kidney failure or death.

There are some reports of statins occasionally producing cognitive effects (difficulty with concentration or thought), and some reports suggest a slight increase in the risk of cancer. (Notably, however, other studies have suggested a reduction in the risk of cancer with statins). Neither of these possibilities is widely accepted by experts.

Who should take statins?

Controversy has erupted over the question of how important it really is to reduce cholesterol levels, and it is likely to take quite some time before this controversy is fully resolved. In the meantime, however, we actually know a lot about reducing cardiac risk, and the role that statins play in reducing that risk. Whether the effect of statins turn out to be primarily through their cholesterol-lowering or through one or more of their other beneficial effects, statins clearly and substantially improve cardiac outcomes in certain individuals.

Here's where the statins fit in in improving your cardiac risk:

1) For everyone: take every available non-pharmacologic opportunity to reduce cardiac risk, including weight control, a good diet, plenty of exercise, not smoking, blood pressure control, and (admittedly controversial but reasonably well-documented) moderate alcohol (i.e., at least one drink per week, but no more than two drinks per day). These measures will reduce your cholesterol levels, but more importantly, they'll substantially reduce your risk despite your cholesterol levels.

2) For patients with established CAD: statin therapy. Note that here, statins are recommended for their risk-reduction effects essentially without regard to baseline cholesterol levels. Treat the risk, not the cholesterol.

3) For patients at high risk for CAD: aggressive risk factor control, and discuss the utility of statin therapy with your doctor. Note that the use of statins for primary prevention (i.e., in patients who do not have proven CAD) in women and in people 70 or older is less well established than in younger men.

4) For patients with LDL cholesterol levels currently recommended for treatment according to latest guidelines, and who do not have established CAD: first try non-prescription control, and if that fails discuss statin therapy with your doctor.

5) For patients who should be considered for statin therapy (see items 2 - 4) but who cannot tolerate statins: Consider alternate pharmacologic therapy to reduce cholesterol, keeping in mind that the scientific evidence for such therapy is less well established.