Statins can help prevent blood clots

Among other benefits, statins can help prevent blood clots

Harvard Health Letters

For a young physician just entering practice today, life before the statins must seem like the dark ages of cardiology. Since the first statin was approved in 1987, these important medications have improved the outlook for millions of Americans with heart disease or cardiac risk factors.

All in all, statins can reduce the risk of heart attacks and other major clinical manifestations of coronary artery disease (CAD) by up to 37 percent. And since heart disease is America's leading cause of death, it's no wonder that the seven statin drugs are the best-selling prescription medications in the United States.

TARGETING CHOLESTEROL

All seven statin drugs act in the same way, by inhibiting the activity of 5-hydroxy-3-methylglutaryl coenzyme A reductase, a liver enzyme that's better known by its short name HMG-CoA reductase. By either name, it's the key enzyme responsible for cholesterol production. When the enzyme is blocked, liver cells make less cholesterol, and blood levels of LDL ("bad") cholesterol fall. But these drugs have another benefit: as cholesterol production falls, the liver takes up more cholesterol from the blood, so blood levels fall even further.

The statins produce only small elevations in HDL ("good") cholesterol, and only atorvastatin and rosuvastatin lower triglycerides, another potentially "bad" lipid, to an important degree.

BEYOND CHOLESTEROL

While the statins' effects on blood cholesterol levels get (and deserve) most of the attention, these powerful medications have many other actions that may protect the heart. In round numbers, a 40-milligrams per deciliter drop in LDL cholesterol produces a 20 percent reduction in coronary deaths. But an exciting 2008 report found that statins may also protect cardiovascular cells directly by speeding DNA repair and slowing cell death. If similar effects occur in other cells as well, they might help explain the nonvascular benefits of statins.

The statins also have anti-inflammatory and antioxidant properties that may protect the arterial wall from being damaged by cholesterol. In addition, they improve vascular function, helping arteries widen to carry more blood to the heart muscle and other tissues. And the statin drugs stabilize cholesterol-laden arterial plaques, reducing the chance that they will rupture and trigger heart attacks.

By inhibiting platelets, the tiny blood cells that initiate blood clotting, statins also help to prevent artery-blocking blood clots. Finally, statin therapy appears to reduce blood viscosity, or "thickness," perhaps facilitating flow through partially blocked arteries.

TARGETING HEART DISEASE

Based on large randomized clinical trials and extensive clinical experience, the U.S. Food and Drug Administration has approved the statin drugs to lower high cholesterol (and in some cases, triglyceride) levels and to prevent cardiac events in patients with coronary artery disease or major cardiac risk factors, regardless of their initial cholesterol levels. Many practitioners also extend the use of statins to other patients with various forms of atherosclerosis.

Beyond the coronary arteries

Although the statins deserve their reputation as "heart drugs," they have the potential to affect many organs and tissues. That's no surprise, since every part of the body depends on arteries to supply oxygen-rich blood; every cell in the body is surrounded by a cholesterol-rich cell membrane; vitamin D and the steroid hormones (including cortisol and the male and female sex hormones) are built on a backbone of cholesterol; and the statins have so many actions beyond cholesterol itself.

The widespread actions of the statins also account for the negative effects that can impact many different functions. Fortunately, these adverse reactions are uncommon, and they are generally mild and reversible. Examples include intestinal distress, rashes, liver inflammation, muscle inflammation, aching joints, sleep disorders, headaches, and erectile dysfunction.

Only a small percentage of statin users experience significant side effects, but it's worth remembering that an eighth statin, cerivastatin (Baycol), was withdrawn in 2001 because of severe muscle damage.

If the statins can produce such diverse side effects, is it possible that they also have diverse "side benefits" unrelated to cholesterol and the coronary arteries? A large number of medical studies suggest the answer is yes, with statin drugs getting credit for reducing the risk of conditions ranging from cataracts and prostate cancer to gallstones and chronic lung disease. While these possibilities are intriguing, none has been proven. But before we review the research on noncoronary effects of statins, we should remember the limitations of these studies.

Some claims for possible benefits are based on laboratory experiments in which statin drugs are added to tissue cultures. These experiments show that diverse biological actions of statins are plausible, but they don't necessarily translate into clinical reality.

Some claims are based on animal studies. These, too, are interesting, but there is no assurance that people will react like mice.

Most claims are based on observational studies in which scientists compare the health status of patients taking statin drugs with similar individuals who are not on these medications. Observational studies can establish associations, but they can never prove causality; in other words, it's nice to know that people who take statins are less likely to develop vision-robbing age-related macular degeneration than people who don't take statins, but that doesn't necessarily mean that the statins are responsible for the apparent protection.

Observational studies may also be confounded by the "healthy user effect." For example, early studies linked taking vitamin E with a reduced risk of heart disease, but randomized clinical trials (the gold standard of methods for investigating drugs) subsequently proved that the supplements were not at all beneficial. Perhaps, then, the people who took supplements were also more diligent about eating well, exercising regularly, not smoking, drinking alcohol in moderation, and getting medical care.

Scientists do their best to account for these differences, but in observational studies, it's nearly impossible to entirely exclude the healthy user effect. Finally, many of the studies are small, brief, or otherwise preliminary.

Despite these limitations, studies of how statins might affect various diseases are of obvious interest to the many people who take these highly popular medications. And it's even possible that some of the studies actually underestimate possible benefits because they're too small or brief or don't discriminate between statin drugs that may behave differently. For example, while all statins inhibit HMG-CoA reductase in the liver, there are other differences between them that could impact each drug's actions.

The statins are complex drugs with many actions. They're of proven benefit for reducing the risk of heart attacks and cardiovascular deaths, and a large body of research suggests they may also have important benefits beyond the coronary arteries. - Harvard Men's Health Watch

STATIN DRUGS

1. Lovastatin (generic, Altoprev, Mevacor)

Introduced 1987

Tablet sizes: 10-60 mg

Typical decrease in LDL cholesterol: 20 percent-45 percent

2. Pravastatin (generic, Pravachol)

Introduced 1991

Tablet sizes: 10-80 mg

Typical decrease in LDL cholesterol: 30 percent-40 percent

3. Simvastatin (generic, Zocor)

Introduced 1992

Tablet sizes: 5-80 mg

Typical decrease in LDL cholesterol: 35 percent-50 percent

4. Fluvastatin (Lescol)

Introduced 1994

Tablet sizes: 20-80 mg

Typical decrease in LDL cholesterol: 20 percent-38 percent

5. Atorvastatin (Lipitor)

Introduced 1997

Tablet sizes: 10-80 mg

Typical decrease in LDL cholesterol: 35 percent-60 percent

6. Rosuvastatin (Crestor)

Introduced 2003

Tablet sizes: 5-40 mg

Typical decrease in LDL cholesterol: 45 percent-60 percent

7. Pitavastatin (Livalo)

Introduced 2010

Tablet sizes: 1-4 mg

Typical decrease in LDL cholesterol: 30 percent-45 percent

STATIN VS. STATIN

1. Origins

Natural: lovastatin, pravastatin, simvastatin

Synthetic: fluvastatin, atorvastatin, rosuvastatin, pitavastatin

2. Absorption

Lovastatin absorbed best with food

Pravastatin absorbed best on an empty stomach

3. Distribution

Fat-soluble, enters the brain: lovastatin, simvastatin, atorvastatin, pitavastatin

Water-soluble, doesn't enter the brain: pravastatin, fluvastatin, rosuvastatin

4. Elimination

Rapid; should be taken in the evening: lovastatin, pravastatin, simvastatin, fluvastatin

Slow; may be taken morning or night: atorvastatin, rosuvastatin, pitavastatin

5. Excretion by kidneys

High: pravastatin (reduce dose in kidney disease).

Moderate: lovastatin, simvastatin, rosuvastatin, pitavastatin (reduce dose in severe kidney disease).

Low: fluvastatin, atorvastatin (no dose adjustment for kidney function).

6. Effect on trigylcerides

Little change: lovastatin, pravastatin, simvastatin, fluvastatin

Moderate lowering: atorvastatin, rosuvastatin, pitavastatin

7. Interaction with other drugs

Few: pravastatin

Moderate: the other statins

8. Interactions with grapefruit juice

Levels boosted: pravastatin, rosuvastatin

Levels unchanged: lovastatin, simvastatin, fluvastatin, atorvastatin, pitavastatin

9. Metabolism in people of Asian descent

Higher blood levels: rosuvastatin

Normal blood levels: the other statins

 

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