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

Abstract

Objective: 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. We sought to study the effect of fenofibrate (vs. placebo) in HF outcomes among patients with T2D receiving simvastatin enrolled in the Action to Control Cardiovascular Risk in Diabetes lipid trial (ACCORD Lipid).

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

Results: A total of 5,518 patients were included. Median age was 62 years, and 31% were women. 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 (Pinteraction = 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 estimated glomerular filtration rate (eGFR) events but slowed long-term eGFR decline.

Conclusions: 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.

Figure 1

Time to first events of the composite of HF hospitalization or cardiovascular death by subgroups of glucose-lowering strategies. HR 0.64, 95% CI 0.48–0.85, among patients randomized to a standard glucose-lowering strategy and HR 1.02, 95% CI 0.79–1.33, among patients randomized to an intensive glucose-lowering strategy (P_interaction = 0.017). Fibrate, fenofibrate.