Diabetes and Metabolism Effects of fenofibrate on cardiovascular events in patients with diabetes, with and without prior cardiovascular disease: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study Andrew Tonkin, MD, a,j,k David Hunt, MD, b,j,k Merryn Voysey, MBiostat, c,k Antero Kesäniemi, MD, d,k Andrew Hamer, FRACP, e,k Jonathon Waites, FRACP, f,k Leo Mahar, FRACP, g,k Stewart Mann, MD, h,k Paul Glasziou, PhD, i,k Peta Forder, MBiostat, c,k,l John Simes, MD, c,k and Anthony C. Keech, FRACP c,k Melbourne, Sydney, Coffs Harbour, Adelaide, and Gold Coast, Australia; Oulu, Finland; and Nelson, and Wellington, New Zealand Background In the FIELD study, comparison of the effect of fenofibrate on cardiovascular disease (CVD) between those with prior CVD and without was a prespecified subgroup analysis. Methods The effects of fenofibrate on total CVD events and its components in patients who did (n = 2,131) and did not (n = 7,664) have a history of CVD were computed by Cox proportional hazards modeling and compared by testing for treatment-by-subgroup interaction. The analyses were adjusted for commencement of statins, use of other CVD medications, and baseline covariates. Effects on other CVD end points were explored. Results Patients with prior CVD were more likely than those without to be male, to be older (by 3.3 years), to have had a history of diabetes for 2 years longer at baseline, and to have diabetic complications, hypertension, and higher rates of use of insulin and CVD medications. Discontinuation of fenofibrate was similar between the subgroups, but more patients with prior CVD than without, and also more placebo than fenofibrate-assigned patients, commenced statin therapy. The borderline difference in the effects of fenofibrate between those who did (hazard ratio [HR] 1.02, 95% CI 0.86-1.20) and did not have prior CVD (HR 0.81, 95% CI 0.70-0.94; heterogeneity P = .045) became nonsignificant after adjustment for baseline covariates and other CVD medications (HR 0.96, 95% CI 0.81-1.14 vs HR 0.78, 95% CI 0.67-0.90) (heterogeneity P = .06). Conclusions Our findings do not support treating patients with fenofibrate differently based on any history of CVD, in line with evidence from other trials. (Am Heart J 2012;163:508-14.) In people with diabetes, who are already at higher risk of cardiovascular disease (CVD), a prior CVD event more than doubles the risk of having a major CVD event and approximately triples the risk of cardiovascular death. 1 Cholesterol-lowering treatments may be used to modify the characteristic diabetic dyslipidemic pattern. 2 People with type 2 diabetes have low high-density lipoprotein (HDL) cholesterol levels and high triglyceride levels, 3,4 both of which are associated with higher risks of coronary heart disease (CHD). 5-7 Fibrates are more effective in reducing triglyceride levels and possibly raising HDL cholesterol levels than 3-hydroxy-3-methylglutaryl-coenzyme A (HMG- CoA) reductase inhibitors (statins) 8,9 and may reduce CVD in people with diabetes. 10-12 In the FIELD study, treatment with fenofibrate compared with placebo over an average of 5 years resulted in a nonsignificant 11% relative risk reduction (95% CI -5% to 25%) in the primary outcome, coronary From the a Department of Epidemiology and Preventive Medicine, Monash University, Melbourne,Vic,Australia, b Department ofCardiologyand UniversityofMelbourneDepartment of Medicine, Royal Melbourne Hospital, Melbourne, Vic, Australia, c NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia, d Institute of Clinical Medicine, Department of Internal Medicine and Biocenter Oulu, University of Oulu and Clinical Research Center,OuluUniversityHospital,Oulu,Finland, e NelsonHospital,Nelson,NewZealand, f Coffs Harbour Cardiovascular Clinic, Coffs Harbour, NSW, Australia, g Cardiology Clinical Trials Unit, Royal Adelaide Hospital, Adelaide, SA, Australia, h Department of Medicine, University of OtagoWellington,Wellington,NewZealand, i Centre for Research in Evidence-Based Practice, Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Qld, Australia. j Equal first authors. k On behalf of the FIELD Study Investigators. l Now at Priority Research Centre for Gender, Health and Ageing, University of Newcastle, NSW, Australia. Reg no. ISRCTN 64783481. Submitted July 28, 2011; accepted December 14, 2011. Reprint requests: Andrew Tonkin, MD, and Anthony C. Keech, FRACP, NHMRC Clinical Trials Centre, Building K25, 92–94 Parramatta Road, Camperdown NSW 2050, Australia. E-mail: tony@ctc.usyd.edu.au 0002-8703/$ - see front matter © 2012, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2011.12.004