The Use of Lipid-Lowering Drugs for Primary Prevention of Coronary Heart Disease
Abstract & commentary
Synopsis: Primary prevention using statin drugs reduces the incidence of coronary heart disease events but not all-cause mortality.
Source: Pignone M, et al. BMJ 2000;321:983-986.
The effectiveness of drug treatment for lipid disorders in patients with no history of coronary heart disease (CHD) has been controversial. Pignone and colleagues point out that a recent review of lipid-lowering treatment with statins found that CHD events and all-cause mortality were decreased in primary prevention populations.1 Also, new data from the large Air Force/Texas coronary artery prevention study, which examined women and men with poor ratios of total cholesterol (TC) to high-density cholesterol (HDL) and modest risk (0.5-1%), found that lovastatin reduced the risk of the first major coronary event.2
Pignone et al searched the Medline database from January 1994 to June 1999 for English language studies examining drug treatment for lipid disorders. The inclusion criteria were all randomized trials of at least one year’s duration that examined drug treatment for patients with no known CHD, cerebral vascular disease, or peripheral vascular disease, and measured all-cause mortality, CHD mortality, and nonfatal myocardial infarction.
Four studies met the criteria. Drug treatment reduced the odds of a CHD event by 30%, but not the odds of all-cause mortality. When statin drugs were considered alone, no substantial differences in the results were observed.
They concluded that treatment with lipid-lowering drugs lasting 5-7 years reduces CHD events but not allcause mortality.
Comment by Ralph R. Hall, MD, FACP
These studies are interesting for a number of reasons. The Airforce/Texas study supports the inclusion of HDL in the risk factor assessment by the National Cholesterol Education Program guidelines. A number of investigators have advocated the inclusion of HDL for some time. Also, all-cause mortality was not increased as it has been in some studies.
The long-term use of these drugs, as well as the use of fibrates, which have also been successful in patients with low HDL levels, is still of some concern.
Newspapers throughout the country have reported that the Food and Drug Administration rejected proposals by the manufacturers of lovastatin and pravastatin to make these drugs available over the counter.
As noted by Hulley and colleagues in an editorial, the arguments for allowing over-the-counter sales were that statins are effective, easy to take, relatively safe, and many people who should take the drugs are not doing so.3
The underuse of statins is most apparent in secondary prevention of patients with known heart disease. Only about one-third of the patients with elevated lipids are treated after they have had a myocardial infarction and many of those treated are not treated until the recommended goals for lipid lowering have been attained.
One note of caution is indicated for physicians who recommend long-term therapy with the statins—the potential for tachyphylaxis. A recent study of atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin demonstrated that LDL tachyphylaxis appeared to be a unique response to prolonged use of atorvastatin at the doses usually given.4
References
1. Hebert PR, et al. JAMA 1997;278:313-321.
2. Downs JR, et al. JAMA 1998;279:1615-1622.
3. Hulley SB, et al. BMJ 2000;321:971-972.
4. Cromwell WC, Ziajka PE. Am J Cardiol 2000;86:
1123-1127.
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