Fibrates for patients without established cardiovascular disease

Cochrane: What are the benefits and harms of using fibrate treatment compared to placebo or usual care for preventing cardiovascular disease in people at increased risk of developing cardiovascular disease? Cardiovascular disease is the most common cause of death, illness, disability, and reduced quality of life in industrialised countries. One of the major risk factors for cardiovascular disease is elevated low-density lipoprotein cholesterol (LDL-C, 'bad' cholesterol). In addition, persons with elevated serum triglycerides and low levels of high-density lipoprotein cholesterol (HDL-C, 'good' cholesterol) are also at increased risk for cardiovascular disease events such as heart attacks or strokes. Fibrates lower serum triglycerides, modestly raise HDL-C, and modestly lower LDL-C.
Therefore, long-term therapy with fibrates may help prevent cardiovascular disease events, in particular in combination with statins, for which it has been shown that they substantially lower LDL-C and reduce the risk of heart attack, stroke, and overall mortality.
Study characteristics
The evidence is current to May 2016. We identified six eligible primary prevention trials including 16,135 individuals without established cardiovascular disease that compared fibrate therapy with placebo or usual care. The mean age of the trial populations varied between 47.3 and 62.3 years; the majority of included individuals had diabetes mellitus type 2. The mean treatment duration and follow-up of participants across trials was 4.8 years.
Key results and quality of the evidence
Moderate-quality evidence suggests a risk reduction of 16% with fibrate therapy for the combined outcome of death due to cardiovascular disease, heart attack, or stroke. In absolute terms, the risk for this combined outcome in patients with cardiovascular risk factors but without established cardiovascular disease was on average reduced from 5.0% to 4.3% over five years. Moderate-quality evidence also suggests a risk reduction for fatal and non-fatal heart attacks with fibrates, but there is low-quality evidence for no risk reduction for overall mortality or death from non-CVD with fibrates. Very-low quality evidence suggests that there is no increased risk for adverse effects with fibrate treatment. The reporting of adverse effects by identified trials was very limited. Data on quality of life were not available from any included study. Trials that evaluated fibrates in the background of statin treatment showed no benefits in preventing cardiovascular events.

Authors' conclusions: 

Moderate-quality evidence suggests that fibrates lower the risk for cardiovascular and coronary events in primary prevention, but the absolute treatment effects in the primary prevention setting are modest (absolute risk reductions < 1%). There is low-quality evidence that fibrates have no effect on overall or non-CVD mortality. Very low-quality evidence suggests that fibrates are not associated with increased risk for adverse effects.