Cardiovascular Risk, Renal Status and Fenofibrate Safety in the FIELD Study

Background: Baseline renal function predicts cardiovascular disease (CVD). In the FIELD study, fenofibrate raised plasma creatinine. We examined the effect of renal status changes on CVD risk and the consequences of fenofibrate administration in moderate renal impairment. Methods: In FIELD, 9795 patients, 50–75 years with type 2 diabetes, were randomly assigned fenofibrate 200 mg daily or placebo over five years. The pre-specified outcome for subgroup analysis was total cardiovascular events. Renal status [eGFR (MDRD) and albuminuria (albumin:creatinine ratio)] was examined (baseline, year 2 and close-out). End-stage renal events were recorded. Analysis was by intention-to-treat. Results: CVD risk was strongly associated with baseline eGFR (inverse) and albuminuria; and was modified by renal status changes over the first two years. In those whose albuminuria status changed from normal to abnormal, risk significantly increased (p = 0.006) whereas it reduced when albuminuria resolved (p = 0.01). A similar pattern was observed for changing eGFR status between <60 and ≥60 ml/min/1.73 m2. Overall, fenofibrate reduced total cardiovascular events by 11% (p = 0.035), with comparable benefits seen in all eGFR subgroups (p-interaction = 0.2). The greatest absolute CVD risk reduction (7.5%) was observed with baseline eGFR 30–59 ml/min/1.73 m2 (HR 0.68, p = 0.035). End-stage renal disease events were no more common with fenofibrate. Conclusions: Improvements in eGFR and albuminuria over time are associated with lower CVD risk. Fenofibrate slows eGFR loss and does not cause renal injury in diabetes or reduce cardiovascular benefits when creatinine rises. There were large cardiovascular benefits and no renal issues when used in those with moderate renal impairment.