Background: Fenofibrate increases renal clearance of uric acid (UA). Relationships between baseline and short-term changes in plasma UA with fenofibrate and subsequent cardiovascular risk in patients with type 2 diabetes (T2D) are unknown.
Method: Post hoc analyses of the FIELD trial explored the relationships between CVD events and 1) baseline UA level; and 2) short-term change in UA level over 6-week single-blind active fenofibrate run-in.
Results: The FIELD trial showed 11% fewer cardiovascular events in patients with T2D assigned to fenofibrate compared to placebo over 5 years (HR = 0.89, 95% CI: 0.80-0.99, p = 0.035). Baseline UA (n=9622) ranged between 0.11 to 0.79 mmol/L (mean = 0.33, SD = 0.078). Each 0.1 mmol/L higher baseline UA increased CVD events by 21% (HR = 1.21 95% CI: 1.13-1.29, p < 0.001; Fig. 1A), and remained after adjusting for other classic risk factors (HR = 1.12, 95% CI: 1.04-1.21, p = 0.002). Fall in UA level with fenofibrate run-in also predicted lower CVD risk, adjusted for baseline UA and irrespective of trial treatment allocation (HR = 0.86, 95% CI: 0.76-0.97, p = 0.015; Fig. 1B).
Discussion: Baseline and short-term fenofibrate-induced lowering of UA predict cardiovascular risk in patients with T2D, irrespective of long-term trial treatment allocation. The reduction in total CVD events with fenofibrate was not shown to be mediated through lowering of UA levels.
J.Y. Cao: None. B. Waldman: None. R.L. OConnell: None. D. Sullivan: None. V. Gebski: None. A.S. Januszewski: None. I. Marschner: None. R. Scott: None. M. Taskinen: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Akcea Therapeutics, Chiesi USA, Inc. Research Support; Self; Amgen Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; Amgen Inc. R. Simes: None. N. McGill: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.C. Keech: None.
