Cholesterol-lowering drugs
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Coromary heart disease (CHD) is the leading cause of death for men and women in the United States. There's a direct relationship
between cholesterol levels and the risk of death due to CHD. Statin medications inhibit cholesterol synthesis and reduce cholesterol
levels substantially. In controlled trials of patients who have heart disease, they have reduced mortality by 30% to 40%.
Lipitor, made by Pfizer, is the best-selling medicine in the world. According to NDCHealth, its 12-month U.S. sales reached
$8.1 billion.
Statin medications include:
- Altocor (lovastatin extended release)
- Crestor (rosuvastatin)
- Lescol (fluvastatin)
- Lipitor (atorvastatin)
- Mevacor (lovastatin)
- Pravachol (pravastatin)
- Zocor (simvastatin)
"Statins are the lipid-regulating drugs of first choice for most patients at risk for coronary and other atherosclerotic vascular
disease," says Mark Abramowicz, MD, editor of The Medical Letter on Drugs and Therapeutics. "Some studies indicate that high-risk patients, such as diabetics, may benefit from taking a statin even if they have no
lipid abnormalities."
Lifestyle changes such as lowering weight, eating less saturated fat, and exercising more are the first line of defense against
heart disease. Many MCOs offer disease management programs for those at high risk for heart disease, and these programs include
nutritional counseling and similar support services. When these measures have been tried, but cholesterol levels remain high,
it's time to turn to medications.
Statins generally have few side effects. Patients who cannot tolerate one statin may tolerate another, so a formulary should
include a variety of options.
"Most MCOs do have two or more statins on their formulary," says Mark N. Brueckl, RPh, MBA, pharmacy affairs manager for the
Academy of Managed Care Pharmacy.
Side effects may include mild gastrointestinal problems, headaches or rashes. Muscle weakness can occur. On occasion, rhabdomyolysis
(muscle wasting) has been reported, which can lead to kidney failure. It is more common with higher doses of statins. In 2001,
Bayer removed its statin drug, Baycol, from the market because it had unacceptable levels of rhabdomyolysis, resulting in
31 reported deaths.
CHANGING GUIDELINES In July 2004, the National Cholesterol Education Program released new guidelines for people at highest risk (those who've
already had a heart attack). Until now, the treatment goal for these patients was an LDL level of 100; the new guidelines
suggest reducing LDL down to 70. In addition, for people at moderately high risk (10% to 20% chance of a heart attack in the
next 10 years), medication use to lower LDL below 100 should be seriously considered. This means statins, which are the most
commonly used type of cholesterol lowering medication, are now recommended for several million people who haven't been taking
them, and higher doses are recommended for many of those who are already taking them.
However, the new guidelines have generated questions and opposition. The Center for Science in the Public Interest as well
as a number of influential physicians say there isn't enough evidence to justify the new guidelines, and that guideline authors
appear to have undisclosed conflicts of interest.
COMBINATION DRUGS When patients still have high lipid levels even after statin treatment, it makes sense to add a second drug with a different
mechanism. Zetia (ezetimibe) is a cholesterol absorption inhibitor. Vytorin, recently approved by the FDA, combines Zetia
and Zocor in a formulation that costs less than taking the two drugs separately. "When you use two drugs with two different
mechanisms, you may avoid the dose-related side effects of both," Dr. Abramowicz says. "However, statins have other effects
in addition to lowering cholesterol; in particular, they have an anti-inflammatory effect. Even when Vytorin reduces cholesterol
levels, it's not clear whether it will improve clinical outcomes as much as a similar reduction achieved through statins alone.
This is a crucial question, and expert opinion differs on this point." Merck and Schering-Plough recently announced a new
clinical trial which will follow 10,000 people for two years, to find out whether Vytorin does improve clinical outcomes.
ON THE HORIZON One generic statin, lovastatin, is already on the market. In addition, Pravachol, from Bristol-Myers Squibb, will probably
go off patent in April 2006. Zocor, from Merck, is scheduled to go off patent in June 2006.
Last summer, Johnson & Johnson/ Merck began selling a 10 milligram version of Zocor over the counter in the United Kingdom,
the first country to allow non-prescription sales of statins. Other countries will be watching closely. Potential benefit:
wider use. Potential risk: People may take the drug who don't really need it, or who would be better off trying diet and
exercise first. In an editorial in the Sept. 15 issue of the American Journal of Cardiology, Antonio M. Gotto, Jr., MD, dean of Weill Cornell Medical College, writes that "OTC availability of low-dose statin therapy
may be a viable complement to therapeutic lifestyle changes in certain intermediate-risk, primary-prevention patients ...
The United Kingdom's decision to permit OTC statins makes the debate a timely and important one for the United States."
This article is based on information supplied by The Medical Letter, (www.medicalletter.org) a nonprofit organization that publishes newsletters offering critical appraisals of new drugs and comparative reviews of older
drugs. The Medical Letter is completely independent of the pharmaceutical industry. It is supported entirely by subscription
sales and accepts no advertising, grants or donations. Institutional site license inquiries can be sent to info@medicalletter.org
.
