Health benefits of fibrate add-on detected postprandially

Adding fenofibrate to statin treatment significantly improves postprandial triglyceride (PPTG) response over statin treatment alone in individuals with diabetes, show findings from a US study.

Furthermore, in contrast to findings from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial in which only dyslipidemic individuals were shown to benefit from the add-on treatment, the present study showed a similar lipid-lowering effect in all participants compared with placebo.

However, in the ACCORD Lipid trial, fasting TG level was used as a predictive measure for cardiovascular disease (CVD), as opposed to the PPTG level used in the current study.

"Recent observations that nonfasting or PP TG levels may be better predictors of CVD risk suggested that examination of the effects of fenofibrate on PPL [postprandial lipids] might provide new insights regarding the outcomes in ACCORD Lipid," explain Henry Ginsberg (Columbia University Medical Center, New York) and colleagues.

In a study including 139 of the original trial participants, the team measured the incremental area under the curve (IAUC) for total plasma TG, apolipoprotein B (apoB) 48, and plasma apoC-III, at 3, 5, 7, and 10 hours after the individuals had consumed a high-fat beverage. The participants had been randomly allocated to receive 20 or 40 mg/day simvistatin plus either 145 mg/day fenofibrate or placebo for a period of at least 4 months prior to undergoing the assessment.

As reported in Diabetes Care, the fenofibrate group had a significant reduction in the IAUC for PPTG and apoB48 compared with the placebo group, at median levels of 572 versus 770 mg/dL per hour and 23.3 versus 35.3 µg/mL per hour, respectively. Plasma apoC-III levels did not differ significantly between the fenofibrate and placebo groups.

The team reports that fasting TG levels positively correlated with the IAUC for PPTG in both the fenofibrate and the placebo group.

However, after further analysis adjusting for fasting TG levels, the researchers still observed a significant effect of fenofibrate on the PPTG and apoB48 response.

Furthermore, the fenofibrate group had a lower IAUC for PPTG across the entire range of fasting TG levels. By contrast, the effect of fenofibrate on the response of apoB48 was significantly modified by fasting TG Level, with levels only reduced when fasting TG levels were increased.

"These results may have implications for interpretation of the overall ACCORD Lipid trial, which suggested benefit from FENO-S (fenofibrate plus simvistatin) only in dyslipidemic individuals," concludes the team.

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