Association of fenofibrate therapy with cardiovascular events and mortality in diabetes patients with early-diagnosed hyperlipidemia

The age at hyperlipidemia diagnosis has been reported to be associated with cardiovascular disease and mortality. This exploratory post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial investigated whether the age at diagnosis of hyperlipidemia influences the effect of adding fenofibrate versus placebo to simvastatin on cardiovascular outcomes and all-cause mortality in diabetes patients. Participants (n = 3861) were stratified into early- (≤ 60 years old) and late-diagnosed (> 60 years old) hyperlipidemia group based on self-reported year of hyperlipidemia diagnosis. Fenofibrate significantly reduced all-cause mortality risk in the early-diagnosed group (HR = 0.57, 95% CI 0.41–0.79) but not in the late-diagnosed group (HR = 1.12, 95% CI 0.81–1.55; P for interaction = 0.006). Similarly, fenofibrate reduced major adverse cardiovascular events (MACEs) risk in the early-diagnosed group (HR = 0.69, 95%CI 0.55–0.88), with a non-significant trend in the late-diagnosed group (HR = 0.86, 95%CI 0.64–1.16; P for interaction = 0.256). Notably, the reduction in MACEs risk was driven primarily by a significant decrease in death from cardiovascular causes among early-diagnosed hyperlipidemia group (HR 0.47, 95% CI 0.30–0.74; P for interaction = 0.07), whereas no significant benefit was observed for nonfatal myocardial infarction or stroke. These findings suggest that fenofibrate use is associated with lower cardiovascular events and mortality risk specifically in diabetes patients with early-diagnosed hyperlipidemia.