Clinical Question: Does therapy aimed at raising the level of high-density lipoprotein (HDL) cholesterol provide a benefit in patients with heart disease?

Setting: Outpatient (any)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: The authors of this meta-analysis identified 83 randomized controlled trials enrolling more than 21,000 patients that evaluated the role of HDL-cholesterol–raising therapy with fibrates such as gemfibrozil, clofibrate, fenofibrate, or bezafibrate. The authors searched only MEDLINE and focused only on English-language journals. Unpublished data, review article citations, and other databases were not searched, all of which are now standard practice in meta-analysis. As a result, the authors may have missed studies that did not show a benefit to treatment. All randomized studies lasting at least three weeks were included.

Most of the studies lasted at least eight months and almost all of the outcomes data were from studies enrolling patients with preexisting coronary heart disease or type 2 diabetes. The authors combined all fibrates into one group. On average, treatment of men with a fibrate or niacin decreased the total cholesterol level by approximately 10 percent, increased the HDL cholesterol level by 10 to 16 percent, and reduced triglyceride levels by 20 to 36 percent. Fibrates, in general, decreased the likelihood of a major coronary event over four years (number needed to treat [NNT] = 33; 95 percent confidence interval [CI], 20 to 100) and the risk of coronary death (NNT = 100; 95 percent CI, zero to 100). Cardiovascular deaths and deaths from any cause were not affected by treatment. The authors did not comment on the homogeneity of their data.

Bottom Line: In men with pre-existing heart disease, drug therapy with fibrates aimed at increasing HDL cholesterol levels decreases the likelihood of a major coronary event and decreases the risk of coronary death. Despite being studied in many at-risk men, fibrate therapy has not been shown to decrease the number of overall deaths or cardiovascular deaths. Research evaluating the benefit of therapies aimed at lowering the levels of low-density lipoprotein (LDL) cholesterol and increasing the levels of HDL cholesterol is needed. Until then, physicians should focus on lowering LDL cholesterol levels, because that is where the greater benefit is evident. (Level of Evidence: 1a–)