Larger Effects of Fenofibrate on CVD in Marked Diabetic Dyslipidemia Are Not Explained by Higher Use of Statin Therapy: The FIELD Study

Background: Many patients started statin therapy during the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial of fenofibrate 200 mg daily versus placebo in patients with type 2 diabetes. Objective: We explored whether use of statins may have accounted for larger-than-average observed benefits of fenofibrate on CVD events in those with marked dyslipidemia. Methods: Total CVD events was the prespecified outcome for all subgroup analyses. Marked dyslipidemia was defined as HDL-C levels <40 mg/dL for men or <50 mg/dL for women and triglyceride levels >200 mg/dL at baseline. Penalized Cox model analyses were used to determine the adjusted effect of fenofibrate, by applying evidence-based estimates of statin efficacy derived (from the Cholesterol Treatment Trialists’ Collaboration Study) to each patient who received statins in either treatment arm for the time taken, and then adjusted for full fenofibrate compliance using the discontinuation rates. Results: Among all 9795 study subjects, average on-study use of lipid-lowering therapy (mostly statins) was more common in the placebo group than in those allocated to fenofibrate (17 vs 8%, P<0.0001). Discontinuation (dropout) rates from trial treatment were low and nearly identical in both treatment arms (10 vs 10%, P=ns ). Corresponding rates among the marked dyslipidemia group were 24 vs 14% (P<0.0001) for use of statins and 11 vs 12% (P=ns) for dropouts. Conclusions: Higher than average co-administration of statins and similar fenofibrate discontinuation rates occurred among those with marked dyslipidemia. The effects of fenofibrate were greater after adjustment for statin uptake, overall, and in those with marked dyslipidemia, suggesting an underestimation in the original unadjusted analyses. However, neither differences in statin use nor dropout rates from fenofibrate accounted for the larger reported benefits of fenofibrate observed in the presence of marked dyslipidemia.