Reference: BMJ. 2019 Sep 27
Metabolic syndrome, a cluster of interrelated risk factors, is associated with an increased risk of cardiovascular disease (CVD), CVD mortality, stroke, and all-cause mortality (J Am Coll Cardiol. 2010 Sep 28). Statin therapy is part of standard care for risk reduction in many patients with cardiovascular risk factors. However, no large studies have been performed evaluating the benefit of adding fenofibrate to statin therapy for CVD risk reduction compared to statins alone. Prior studies evaluating fenofibrate, namely the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, concluded that fenofibrate may reduce risk from CVD in a subgroup of patients with atherogenic dyslipidemia (Am J Cardiol. 2007 Jun 18, Cardiovasc Diabetol. 2005 Aug 22). However, it remains uncertain whether fenofibrate can offer additional benefit to patients already on statin therapy in terms of cardiovascular morbidity and mortality.
This propensity-based cohort study evaluated whether fenofibrate as an add-on to statin treatment reduced major cardiovascular events in patients with metabolic syndrome. 29,771 adults aged ≥ 40 years (mean age 62 years) with metabolic syndrome and on statin therapy for ≥ 3 months (from the Korean National Health Insurance Service-Health Screening Cohort) were evaluated (BMJ. 2019 Sep 27). A propensity score for receiving fenofibrate plus statin was calculated for each patient based on demographic and clinical factors, such as blood pressure, alcohol consumption, physical activity, smoking status, pre-existing cardiovascular disease, and use of medications (such as antithrombotic agents and antihypertensives). The propensity score was used to select participants with similar baseline risk characteristics for comparison. A total of 2,156 adults receiving fenofibrate plus statin and 8,549 propensity-matched adults receiving statin-only treatment were included in the analysis. The primary outcome was composite cardiovascular events, including incident coronary heart disease, ischemic stroke, and death from cardiovascular causes.
The incidence of composite cardiovascular events per 1,000 person-years was 17.7 with combined fenofibrate plus statin vs. 22 with statin alone (adjusted hazard ratio 0.74 [95% CI 0.58 to 0.93]). Significance was maintained in the on-treatment analysis. Although the risk point estimate was lower in the combined treatment group for each of the individual components included in the composite cardiovascular events compared to the statin-only group, it did not reach statistical significance.
Although the combination treatment of fenofibrate plus statin was associated with reduced risk of composite cardiovascular events in this study, its clinical significance is unclear, as none of the individual components measured reached statistical significance. This study is also limited by lack of randomization, and therefore a causal relationship between treatment with a statin and fenofibrate and CV events cannot be established. Using a propensity score for matching can introduce bias by assuming there are no confounders after the groups have been matched, thus potentially overestimating the effect of the combined treatment group. Given these limitations, there currently is not enough evidence to routinely prescribe fenofibrate as an add-on to statin treatment for CVD risk reduction in patients with metabolic syndrome.
For more information, see the Metabolic Syndrome in Adults topic in DynaMed.
This Resident Focus was written by Molly Grover, a third year Family Medicine resident at the University of Virginia. She completed medical school at Virginia Commonwealth University and grew up in Virginia. Molly’s interests include women’s health, academic medicine, and refugee care.
Faculty contributions by Katharine DeGeorge, MD, MS.