https://diabetes.acponline.org/archives/2017/01/13/3.htm

Supplemental triglyceride-lowering therapy may lower CVD risk in statin-treated patients with diabetic dyslipidemia, study finds

The rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes was 27% lower in participants with dyslipidemia randomized to fenofibrate than among those randomized to placebo.


Adding triglyceride-lowering treatment (e.g., fenofibrate) to statin therapy may reduce cardiovascular disease (CVD) risk in patients with type 2 diabetes and dyslipidemia, a recent study found.

The study was an extended follow-up of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study, which randomized participants to either fenofibrate or placebo on a background of statin therapy and produced heterogeneous findings about the effect of fenofibrate on CVD outcomes. Results of the ACCORD Follow-On Study (ACCORDION) were published online on Dec. 28, 2016, by JAMA Cardiology.

A total of 4,644 ACCORD-Lipid participants agreed to five years of passive follow-up in ACCORDION. Only 144 participants (4.3%) continued treatment with fenofibrate after ACCORD. The prespecified primary outcome was the first postrandomization occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, or death from cardiovascular causes.

After a mean of 9.0 total years of follow-up, 508 primary endpoint events occurred in the fenofibrate group, compared to 539 in the placebo group (P=0.25).These neutral results essentially mirrored the original findings of the ACCORD study (P=0.32). However, researchers observed significant results in participants with dyslipidemia, defined as triglyceride levels greater than 204 mg/dL (2.3 mmol/L) and high-density lipoprotein cholesterol levels less than 34 mg/dL (0.88 mmol/L).

The rate of the primary outcome in participants with dyslipidemia randomized to fenofibrate was 27% lower than among those randomized to placebo, compared to only a 1% reduction in participants without dyslipidemia (hazard ratio [HR], 0.73 [95% CI, 0.56 to 0.95] vs. 0.99 [95% CI, 0.86 to 1.13]; P=0.05 for dyslipidemic vs. nondyslipidemic, respectively).

Researchers also found sex-based differences in fenofibrate response, which they had also observed in ACCORD. The primary outcome in the fenofibrate group was 16% lower for men but 30% higher for women (HR, 0.84 [95% CI, 0.73 to 0.96] vs. 1.30 [95% CI, 1.10 to 1.68]; P=0.003 for men vs. women, respectively). These differences are “both unexpected and unexplained” and may be a chance finding, the study authors wrote.

“Our findings support the hypothesis that patients with diabetic dyslipidemia may derive some benefit from add-on triglyceride-lowering therapy,” they concluded. In terms of the study's limitations, the authors noted that their prespecified subgroup analyses can only be considered hypothesis-generating and are based on a relatively small number of events in some cases. They added that randomized trials are needed to test the cardiovascular efficacy of fibrates and other triglyceride-lowering treatments in this patient population.