Abundant evidence shows that lowering low-density lipoprotein (LDL) cholesterol concentrations with statins is the primary treatment option for minimising cardiovascular disease in people at risk, including those with atherogenic dyslipidaemia. In many clinical trials and observational studies, substantial cardiovascular risk persisted (residual cardiovascular risk) despite ongoing statin treatment.
Fenofibrate, a peroxisome proliferator-activated receptor-agonist, has been suggested as an important treatment option in the management of dyslipidaemia owing to its effects on hypertriglyceridaemia and low HDL cholesterol concentrations. Although large randomised clinical trials of fenofibrate, including the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial and the Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid trial failed to show a reduction in the primary outcome of major cardiovascular events in populations with diabetes but a statistically significant cardiovascular risk reduction was observed in subgroups with atherogenic dyslipidaemia. Two meta-analyses of fibrates also indicated that the associated reduction of cardiovascular events would benefit people with atherogenic dyslipidaemia.
Kim et al aimed to investigate whether fenofibrate as an add-on to statin treatment reduces persistent cardiovascular risk in adults with metabolic syndrome in a real-world setting.
Participants: 29 771 adults with metabolic syndrome (≥40 years) receiving statin treatment. 2156 participants receiving combined treatment (statin plus fenofibrate) were weighted based on propensity score in a 1:5 ratio with 8549 participants using statin only treatment.
Main outcome measure: Primary outcome was composite cardiovascular events including incident coronary heart disease, ischaemic stroke, and death from cardiovascular causes.
Results: The incidence rate per 1000 person-years of composite cardiovascular events was 17.7 (95% confidence interval 14.4 to 21.8) in the combined treatment group and 22.0 (20.1 to 24.1) in the statin group. The risk of composite cardiovascular events was significantly reduced in the combined treatment group compared with statin group (adjusted hazard ratio 0.74, 95% confidence interval 0.58 to 0.93; P=0.01). The significance was maintained in the on-treatment analysis (hazard ratio 0.63, 95% confidence interval 0.44 to 0.92; P=0.02). The risk of incident coronary heart disease, ischaemic stroke, and cardiovascular death was lower in the combined treatment group than statin group but was not significant. Participant characteristics did not appear to be associated with the low risk of composite cardiovascular events with combined treatment.
Kim NH, Han KH, Choi J et al. Use of fenofibrate on cardiovascular outcomes in statin users with metabolic syndrome: propensity-matched cohort study BMJ 2019;366:l5125.