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Harvard Commentaries
35320
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School


Man to Man Man to Man
 

Your Guide to Statin Drugs


January 22, 2014

By Harvey B. Simon M.D.

Harvard Medical School

Heart disease is the #1 killer of American men. Most often, cholesterol-laden blockages in the coronary arteries pave the way to heart attacks and heart failure. But although heart disease is terribly common, it's not inevitable. You can help beat the rap with:

  • A healthy diet
  • Regular exercise 
  • A tobacco-free life
  • Good control of your blood pressure, blood sugar and cholesterol 

Doctors have been prescribing medication to lower cholesterol for the past 30 years. But in November 2013, the American Heart Association (AHA) and the American College of Cardiology (ACC) issued a game-changing report on cholesterol. 

While the new guidelines support the importance of lifestyle, they also call for doctors to treat abnormal cholesterol levels with a statin drug instead of the other medications approved for cholesterol. And as I reported in last month's column, the AHA-ACC experts identified four groups of people who are likely to benefit from statin therapy:

    1. People with clinical signs of atherosclerosis. This includes everyone who has had angina, a heart attack, a stroke or "mini-stroke" (transient ischemic attack, or TIA), or peripheral artery disease. These patients will benefit from a statin even if they have normal LDL ("bad" cholesterol) levels before treatment. In this group, statin therapy is a form of secondary prevention, meaning it's designed to reduce the likelihood of additional harm from a disease that is already present. In the other groups, though, statins are used for primary prevention, to reduce the odds that heart disease will develop in the first place.
    2. People with LDL cholesterol levels that are dangerously high, 190 mg/dL or above.
    3. People between the ages of 40 and 75 who have diabetes and LDL levels above 70 mg/dL.
    4. People between the ages of 40 and 75 who do not have diabetes or atherosclerosis, but who have LDL levels above 70 mg/dL and an estimated 10-year risk of heart disease of 7.5% or above.

Even if you're not in one of these categories now, you may get there soon. The statins are prescription drugs, so your doctor will help decide if treatment is right for you.  But you should share in this important decision. To help you do your part I'll try to answer your questions about these widely used medications.

What are the statins?

Seven statin medications are approved for use in the United States. They all work in the same way. And they all lower LDL cholesterol quite effectively, but some are more powerful than others (see "Meet the Statins"). They also differ considerably in price, with generic forms being much less expensive than their brand-name twins. 

The statins can reduce the risk of heart attacks and related risks by up to 37%. Men at greatest risk get the most benefit. All seven drugs are generally safe. But there are some subtle differences between them that may help your doctor choose the one that's best for you.

            Meet The Statins

Drug

Year Introduced

Doses (milligrams)

Typical decrease in LDL cholesterol

Lovastatin

(Mevacor, Altoprev, generic)

1987

10-60

20%-45%

Pravastatin

(Pravachol, generic)

1991

10-80

30%-40%

Simvastatin

(Zocor, generic)

1992

5-80

35%-50%

Fluvastatin
(Lescol, generic)

1994

20-80

20%-38%

Atorvastatin

(Lipitor, generic)

1997

10-80

35%-60%

Rosuvastatin (Crestor)

Pitavastatin  (Livalo)

 2003

2010

5-40

1-4

45%-60%

30%-45%

How do they work?

All seven statin drugs target a liver enzyme  known as HMG-CoA reductase. This key enzyme is responsible for cholesterol production. When the enzyme is blocked, liver cells make less cholesterol and blood levels of LDL ("bad") cholesterol fall. But the drugs have another benefit: As cholesterol production falls, the liver takes up more cholesterol from the blood, so blood levels drop even further. The statins produce only small rises in HDL ("good") cholesterol. And only atorvastatin and rosuvastatin lower triglycerides to an important degree.

Other drugs can lower cholesterol. Why are the statins so special?

Lowering cholesterol IS important. In round numbers, a statin that produces a 40 mg/dL drop in LDL cholesterol can reduce coronary deaths by 20%. But unlike other cholesterol-lowering medicines, the stains have other actions that appear to help the heart. They: 

  • May protect cardiovascular cells directly by speeding DNA repair and slowing cell death
  • Have anti-inflammatory and antioxidant properties that may protect the arterial wall from being damaged by cholesterol
  • Help arteries widen to carry more blood to the heart muscle and other tissues
  • Stabilize cholesterol-laden arterial plaques, reducing the chance that they will rupture and trigger heart attacks
  • Inhibit platelets, which helps to prevent artery-blocking blood clots
  • Can reduce blood viscosity or "thickness," perhaps easing blood flow through partially-blocked arteries

Are they safe?

All medications can have side effects, and the statins are no exception. Still, considering the millions of people who have been taking the 7 approved statins for up to 25 years, serious side effects have been remarkably uncommon. 

Muscle aches can develop, but lasting damage is rare. The same is true for the second most common side effect, liver inflammation. Rising blood sugar levels and diabetes is the third major concern, but the benefits for the heart far outweigh the risks of diabetes. 

While there have been occasional reports of mental changes from statins, significant effects on the nervous system appear truly rare. Other infrequent side effects include rashes, intestinal upsets, joint aches, sleep disorders and erectile dysfunction.  And when it comes to other effects, the statins may have helpful "side benefits." There is preliminary evidence that these drugs may help fight prostate cancer and some other tumors, along with stroke, memory loss, lung disease and certain infections.

Most side effects disappear when you stop taking the stain. In many cases, you can safely resume therapy with a lower dose or a different statin. And to minimize problems even further, the new AHA-ACC report asks doctors to maintain routine diabetes surveillance during statin therapy. They should also test levels of a muscle enzyme called CK, if muscle aches or weakness develops. The guidelines also suggest measuring a liver enzyme called ALT before statin therapy and repeating the test if liver symptoms develop.

No man should take a medicine he doesn't need. All men who take a statin should use it with care. With a few simple precautions, these important drugs are safe.  Only a few percent of patients have side effects serious enough to merit stopping therapy.

Which statin drug is best for me? And how long should I take it?

If you are doing well on a statin, you can expect to stay on it indefinitely. Your doctor can help you choose the best drug for you. The AHA-ACC guidelines help by suggesting intensive therapy for people at high risk and moderate-intensity therapy for those at less risk. Intensive therapy requires higher doses and more powerful statins than moderate-intensity therapy. Intensive therapy aims for a reduction in LDL levels of at least 50%, while the goal for moderately-intensive therapy is a 30%-50% drop in LDL.

For the average guy, the decision to take a statin is more important than deciding which statin to take. But some men want to discuss the details of the choices with their doctors. The following information should help.

Type

  • Natural:  lovastatin, pravastatin, simvastatin
  • Synthetic: fluvastatin, atorvastatin, rosuvastatin, pitavastatin

Absorption

  • Best if taken with food: lovastatin
  • Best if taken on an empty stomach: pravastatin
  • Not affected by food: all the rest

Distribution

  • Fat soluble and enters the brain: lovastatin, simvastatin, atorvastatin, pitavastatin
  • Water soluble and doesn't enter the brain: pravastatin, fluvastatin, rosuvastatin

Elimination

  • Rapid: Take in the evening: lovastatin, pravastatin, simvastatin, fluvastatin
  • Slow: Take in the morning or at night: atorvastatin, rosuvastatin, pitavastatin

Excretion by the kidneys

  • High: pravastatin (reduce dose in a person with kidney disease)
  • Moderate: lovastatin, simvastatin, rosuvastatin, pitavastatin (reduce dose in a person with severe kidney disease)
  • Low: fluvastatin, atorvastatin (no dose adjustment needed for a person with kidney function)

Effect on triglycerides

  • Little change: lovastatin, pravastatin, simvastatin, fluvastatin, pitavastatin
  • Moderate lowering: atorvastatin, rosuvastatin

Interaction with other drugs

  • Few: pravastatin
  • Moderate: other statins

Interaction with grapfruit juice

  • Drug levels boosted: atorvastatin, simvastatin, lovastatin
  • Drug levels unchanged: fluvastatin,  pitavastatin, pravastatin, rosuvastatin

Metabolism in people of Asian descent

  • The standard dose of rosuvastatin results in high blood levels of the drug. Half the dose has the same cholesterol-lowering effect. 

If statins are so good, why don't all men take them?

Some doctors think that all men should take statins.  But most experts recommend statins only for people at risk. Unfortunately, in our overweight, sedentary, junk-food loving, high-stress society, millions of men stand to benefit from statins. If you're at risk, you're lucky to have these drugs on your side.  And if you're lucky enough to be at low risk, keep up the good work so you won't ever need a statin.

Back to top

 

Harvey B. Simon, M.D. is an Associate Professor of Medicine at Harvard Medical School and a member of the Health Sciences Technology Faculty at Massachusetts Institute of Technology. He is the founding editor of the Harvard Men's Health Watch newsletter and author of six consumer health books, including The Harvard Medical School Guide to Men's Health (Simon and Schuster, 2002) and The No Sweat Exercise Plan, Lose Weight, Get Healthy and Live Longer (McGraw-Hill, 2006). Dr. Simon practices at the Massachusetts General Hospital; he received the London Prize for Excellence in Teaching from Harvard and MIT.

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