Facts of Life

Facts of Life:
Issue Briefing for Health Reporters
Vol. 12, No. 2
February 2007

Statins: Still Going Strong

The Issue

The Facts

Sizing Up the Side Effects

Expert Sources

References

The Issue:

The cholesterol-lowering medications called statins transformed heart disease care almost two decades ago, but their use is now so widespread and the volume of direct-to-consumer advertising is so loud that consumers deserve a refresher on the advances, claims and side effects of these so-called wonder drugs.

Why So Wonderful?

Too much low-density lipoprotein cholesterol, or "bad cholesterol," in the blood can clog arteries, block blood flow and lead to heart disease and stroke. Statins prompt the liver to draw LDL from the blood, cutting the risk of cardiovascular problems.

Before statins, physicians had less effective tools, some with greater chances of adverse drug reactions. Niacin reduces cholesterol but has many side effects. Bile acid resins are chalky, inconvenient and hard to swallow. "You had to take them three times a day and it was like drinking Ocean City sand," said Simeon Margolis, an endocrinologist with the Johns Hopkins University School of Medicine.

Diligent attention to a healthy lifestyle can drive cholesterol levels down 10 percent to 15 percent. But Margolis said, "The latest statins can lower cholesterol by as much as 50 percent. So they are far, far more powerful and they have very few side effects."

Prevention? Maybe

The evidence is less certain, but mounting, that statins can also ward off heart disease and death in low-risk patients without cardiovascular disease. 1 For those patients, the physicians' first cholesterol-lowering prescription is usually a heart-healthy diet, regular exercise and weight control.

The Facts:

• For adults age 20 and over, a desirable total cholesterol level is less than 200 mg/dL, according to the National Heart, Lung, and Blood Institute of the National Institutes of Health. A level from 200 to 239 is borderline high. A high level is 240 and above.

• More than 11 millions Americans already take a statin and another 25 million people might benefit from treatment, according to federal health advisors. ²

• A 1990s study of more than 4,000 Scandinavian people with heart disease found that simvastatin reduced the rate of coronary heart disease and death. The study paved the way for widespread use of the statin drug class. ³

• According to a 2006 review of studies, mild muscle complaints are reported by 5 percent to 7 percent of patients who take statins. ⁴

• In 2003, London researcher Nicholas Wald suggested that a polypill -- including a statin, blood-pressure-lowering drugs, folic acid and aspirin -- could dramatically cut heart attacks and strokes worldwide. ⁵

• Emerging research suggests that statins benefit a string of conditions including colon cancer, Alzheimer's disease, osteoporosis and arthritis, but the evidence is not solid and is often conflicting. In regular practice, doctors do not use statins to treat or prevent those disorders. ^{6, 7, 8}

• Low-dose statins are available over the counter in the United Kingdom, but in 2005 the U.S. Food and Drug Administration rejected a proposal to make statins available without a prescription.

• A 2005 review of 14 randomized trials including more than 90,000 people found no evidence that statins increase the risk of cancer. ⁹

• In 2002, federal guidelines for cholesterol management lowered the bad-cholesterol threshold that prompts physicians to begin treating patients. The revised guidelines also urged doctors to set target cholesterol levels even lower than was recommended in the past. ²

• Doctors are now beginning to treat acute cardiovascular conditions, like heart attack, aggressively and immediately with high-dose statins to reduce inflammation and stabilize plaque in arteries. ¹⁰

Sizing Up the Side Effects

Muscle aches and liver damage are the side effects most often linked with statins. But physicians and experts say the likelihood of these troubles is very different.

" The liver problems are the ones people worry about most, but what's more common is that people get muscle aches," said Simeon Margolis, an endocrinologist and expert in preventive cardiology with the Johns Hopkins University School of Medicine.

" A lot of people do develop muscle aches that are troublesome, but not dangerous, except in the rare individuals where the muscles get so inflamed that they release proteins that damage the kidneys," he said. That condition, called rhabdomyolysis, is serious but extremely unusual.

"Because of this remote possibility, any responsible doctor is going to say to his patient, 'If you get muscle aches, you have to let me know,'" Margolis said.

High-quality studies show no difference in the muscle aches experienced by people taking a statin and the groups that received a placebo, Margolis said. But initial warnings from doctors may make patients hypervigilant for muscle aches, says cardiologist Philip Barter, director of The Heart Research Institute in Sydney, Australia. Steven Kayser, a clinical pharmacist with the University of California, San Francisco, says coincidence may also boost the number of muscle-ache complaints.

" When patients are started on statins they are simultaneously encouraged to improve their lifestyle and start exercising, so they begin exercising and get sore muscles because they are now performing exercises they haven't performed for many years," Kayser said. "The quick and understandable conclusion is that your new medication is causing the problem."

That assumption may be wrong, but patients should report any muscle problems to their doctor, who can determine if there is a real concern.

According to Barter, serious liver damage associated with statin use is so uncommon that it is difficult to link the problem directly to the drug.

Because statins work with the liver to lower cholesterol levels, doctors do periodic blood tests to monitor how well the liver is working. While true liver damage is unusual, Barter says elevated liver-function readings occur frequently. "It looks like those abnormal levels aren't necessarily due to damage to the liver; they're more likely due to the metabolism of the substances that are being measured," Barter said. Even when liver enzyme levels are boosted above normal levels, "there's no evidence of severe or permanent liver damage."

" Overall, this class of drugs is about as safe as any class of drugs that's ever been developed. Severe side effects are very rare and, alongside their benefits, pale in comparison," Barter said.

Expert Sources:

References

1. Thavendiranathan P, et al. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.

2. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-421.

3. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994 Nov 19;344(8934):1383-9.

4. Arora R, et al. Statin-induced myopathy: the two faces of Janus. J Cardiovasc Pharmacol Ther 2006 Jun;11(2):105-12.

5. Wald NJ, et al. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003 Jun 28;326(7404):1419.

6. Scott HD, et al. Statins for the prevention of Alzheimer’s disease. Cochrane Database Syst Rev 2001;(3):CD003160.

7. Yildirir A, et al. Non-lipid effects of statins: emerging new indications. Curr Vasc Pharmacol 2004 Oct;2(4):309-18.

8. Setoguchi S, et al. Statins and the risk of lung, breast, and colorectal cancer in the elderly. Circulation 2007 Jan 2;115(1):27-33. Epub 2006 Dec 18.

9. Baigent C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005 Oct 8;366(9493):1267-78. Epub 2005 Sep 27.

10. Ray KK, et al. Beyond lipid lowering: what have we learned about the benefits of statins from the acute coronary syndromes trials? Am J Cardiol 2006 Dec 4;98(11A):S18-25. Epub 2006 Sep 29.

The Center for the Advancement of Health is an independent nonprofit organization that promotes greater recognition of how psychological, social, behavioral, economic and environmental factors influence health and illness. The Center advocates the highest quality research and communicates it to the medical community and the public. The fundamental aim of the Center is to translate into policy and practice the growing body of evidence that can lead to the improvement and maintenance of the health of individuals and the public. The Center was founded by the John D. and Catherine T. MacArthur Foundation and the Nathan Cummings Foundation, which continue to provide core funding. Funding for this series was provided by the Robert Wood Johnson Foundation.

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Lisa Esposito
Editor, Health Behavior News Service
Center for the Advancement of Health
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