Fenofibrate and Heart Failure Outcomes in Patients With Type 2 Diabetes: Analysis From ACCORD

Objectives: Patients with type 2 diabetes (T2D) have a high risk for developing heart failure (HF), which is associated with poor prognosis. Fenofibrate may reduce HF events through multiple mechanisms. To study the effect of fenofibrate (vs. placebo) in HF outcomes among patients with T2D receiving simvastatin enrolled in the ACCORD-Lipid trial.

Research design and Methods: Cox regression analysis with background glucose-lowering strategy as stratification variable. The median follow-up was 4.7 years.

Results: A total of 5518 patients were included. The median age was 62 years and 31% were women. A prior HF history was present in 5% of the patients. The composite outcome of HF hospitalization or cardiovascular death occurred in 190 (6.9%) patients in the fenofibrate group vs. 228 (8.3%) in the placebo group: HR 0.82, 95%CI 0.68-1.00, P =0.048. The beneficial effect of fenofibrate to reduce HF hospitalizations or cardiovascular death was present among patients receiving standard glucose-lowering strategy: HR 0.64, 95%CI 0.48-0.85, and not among patients receiving intensive glucose-lowering strategy: HR 1.02, 95%CI 0.79-1.33, interaction P =0.017. A similar pattern was observed for HF hospitalizations alone. The effect of fenofibrate on blood lipids was not influenced by background glucose-lowering therapy in a clinically important manner. Fenofibrate caused more transient worsening eGFR events but slowed the long-term eGFR decline.

Conclusion: In patients with T2D treated with simvastatin, fenofibrate reduced the composite of HF hospitalizations or cardiovascular mortality, an effect that was seen predominantly in patients with standard background glucose-lowering therapy.