Abstract: We identified six eligible trials including 16,135 individuals. The mean age of trial populations varied across trials; between 47.3 and 62.3 years. Four trials included individuals with diabetes mellitus type 2 only. The mean treatment duration and follow-up of participants across trials was 4.8 years. We judged the risks of selection and performance bias to be low; risks of detection bias, attrition bias, and reporting bias were unclear. Reporting of adverse effects by included trials was very limited; that is why we used discontinuation of therapy due to adverse effects as a proxy for adverse effects. Patients treated with fibrates had a reduced risk for the combined primary outcome of CVD death, non-fatal myocardial infarction, or non-fatal stroke compared to patients on placebo (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74 to 0.96; participants = 16,135; studies = 6; moderate-quality of evidence). For secondary outcomes we found RRs for fibrate therapy compared with placebo of 0.79 for combined coronary heart disease death or non-fatal myocardial infarction (95% CI 0.68 to 0.92; participants = 16,135; studies = 6; moderate-quality of evidence); 1.01 for overall mortality (95% CI 0.81 to 1.26; participants = 8471; studies = 5; low-quality of evidence); 1.01 for non-CVD mortality (95% CI 0.76 to 1.35; participants = 8471; studies = 5; low-quality of evidence); and 1.38 for discontinuation of therapy due to adverse effects (95% CI 0.71 to 2.68; participants = 4805; studies = 3; I2 = 74%; very low-quality of evidence). Data on quality of life were not available from any trial. Trials that evaluated fibrates in the background of statins (2 studies) showed no benefits in preventing cardiovascular events. 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.

Plain-language summary: 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. 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.