Metabolic syndrome is a cluster of interrelated risk factors that leads to metabolic dysregulation and atherosclerotic cardiovascular diseases. In many clinical trials and observational studies, substantial cardiovascular risk persisted (residual cardiovascular risk) despite ongoing statin treatment. 

Kim et al (2019) set out to investigate whether fenofibrate as add-on to statin treatment reduce persistent cardiovascular risk in adults with metabolic syndrome in a real-world setting

Kim et al (2019) set out to investigate whether fenofibrate as add-on to statin treatment reduce 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. 

Conclusion  

In this propensity weighted cohort study of adults with metabolic syndrome, the risk of major cardiovascular events was significantly lower with fenofibrate as add-on to statin treatment than with statin treatment alone.  

What is already known on this topic? 

  • Randomised clinical trials of fenofibrate treatment have failed to show a reduction in risk of major cardiovascular events in people with diabetes, but a statistically significant cardiovascular risk reduction was observed in subgroups with atherogenic dyslipidaemia. 
  • Meta-analyses of fibrates also indicated that people with atherogenic dyslipidaemia would benefit from fibrates on cardiovascular events reduction. 
  • Realworld evidence was insufficient to prove the efficacy of fenofibrate in cardiovascular risk reduction especially in people of East Asian origin who are reported to be genetically susceptible to poor elimination of blood triglyceride. 

What this study adds 

  • The risk of major cardiovascular events was reduced in adults with metabolic syndrome using fenofibrate as add-on to statin treatment. 

REFERENCES:  

Kim N H, Han K H, Choi J, Lee J, Kim S G. Use of fenofibrate on cardiovascular outcomes in statin users with metabolic syndrome: propensity matched cohort study BMJ 2019; 366 :l5125 doi:10.1136/bmj.l5125