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QUESTION: In patients with no history of coronary artery disease (CAD), does a lipid lowering drug (cholestyramine, gemfibrozil, pravastatin, or lovastatin) decrease the risk for CAD events, CAD mortality, or all cause mortality?
English language studies were identified by searching Medline (1994 to June 1999) with the Medical Subject Headings (MeSH) hyperlidemia and anti cholesterolemic agents and with MeSH or keywords identifying randomised controlled trials and individual drug names, the Cochrane Clinical Trials Registry, and bibliographies of systematic reviews and clinical practice guidelines.
Randomised controlled trials were selected if they had ≥1 year of duration and measured CAD events, CAD mortality, and all cause mortality. Exclusion criteria were studies of secondary prevention or studies published in abstract form only.
Data were extracted on each drug and its dosage, study duration, population characteristics and size, initial and mean reduction in cholesterol concentrations, CAD events, CAD mortality, and all cause mortality.
4 randomised controlled trials met the inclusion criteria. 21 087 patients (mean age 53 y, 95% men) received a lipid lowering drug (50%) or placebo (50%). Duration was 7 years (1 study) or 5 years (3 studies). The mean initial total cholesterol concentration was ≥7.0 mmol/l in 3 of the 4 trials. Mean reductions in cholesterol concentrations were 8.5% for cholestyramine, 10% for gemfibrozil, and 18% to 20% for high dose statins. Treatment decreased CAD events but not CAD mortality or all cause mortality (table). When analysis was limited to the 2 trials that used statins, the results were similar.
In patients with no history of coronary artery disease (CAD), lipid lowering drugs decrease the risk for CAD events but not CAD mortality or all cause mortality.
The meta-analysis by Pignone et al reinforces the first rule of primary prevention for CAD: absolute reduction in mortality is proportional to overall risk for CAD. Although the authors conclude that “treatment with lipid lowering drugs . . . reduces CHD [sic] events but not all cause mortality in people with no known cardiovascular disease,” they also point out that the West of Scotland Coronary Prevention Study,1 whose participants had a relatively high risk for CAD (8%), had a reduction in all cause mortality with pravastatin. Furthermore, a previous meta-analysis that did not include a trial whose participants were at very low risk also suggested that lipid lowering reduces all cause mortality.2
The meta-analysis by Pignone et al relies on high quality studies but does not give us reliable information on adverse event rates. The results of these studies may not be generalisable to other populations, particularly the elderly and women, because these demographic groups were underrepresented in the trials considered in the meta-analysis.
Lipid lowering was not shown to reduce all cause or CAD mortality in patients at low risk for CAD probably because it takes larger numbers of patients or longer trials to show small, statistically significant absolute reductions in mortality. We have no reason to believe that lipid lowering increases non-coronary mortality. Physicians should continue to consider lipid lowering for primary prevention. As pointed out by the authors, overall CAD risk should be calculated and used to select higher risk patients for treatment with lipid lowering drugs.3 For low risk patients, issues of cost effectiveness may predominate.
Source of funding: Agency for Healthcare Research and Quality.
For correspondence: Dr M Pignone, Division of General Internal Medicine, 5039 Old Clinic Building, University of North Carolina, Chapel Hill, NC 27599-7110, USA. Fax + 1 919 966 2274.