Association of fenofibrate therapy with long-term cardiovascular risk in statin-treated patients with type 2 diabetes

Importance Patients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemiaand low high-density lipoproteincholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk. Objective To determine whether fenofibratereduces CVD risk in statin-treated patients with type 2 diabetes. Design, Setting, and Participants Posttrial follow-up of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study between July 2009 and October 2014; 5 years of follow-up were completed for a total of 9.7 years at general community and academic outpatient research clinics in the United States and Canada. Of the original 5518 ACCORD Lipid Trial participants, 4644 surviving participants were selected based on the presence of type 2 diabetes and either prevalent CVD or CVD risk factors and high-density lipoproteinlevels less than 50 mg/dL ( Interventions Passive follow-up of study participants previously treated with fenofibrateor masked placebo. Main Outcomes and Measures Occurrence of cardiovascular outcomes including primary composite outcome of fatal and nonfatal myocardial infarction and stroke in all participants and in prespecified subgroups. Results The 4644 follow-on study participants were broadly representative of the original ACCORD study population and included significant numbers of women (n = 1445; 31%), nonwhite individuals (n = 1094; 21%), and those with preexisting cardiovascular events (n = 1620; 35%). Only 4.3% of study participants continued treatment with fenofibratefollowing completion of ACCORD. High-density lipoproteinand triglyceride values rapidly equalized among participants originally randomized to fenofibrateor placebo. Over a median total postrandomization follow-up of 9.7 years, the hazard ratio (HR) for the primary study outcome among participants originally randomized to fenofibratevs placebo (HR, 0.93; 95% CI, 0.83-1.05; P  = .25) was comparable with that originally observed in ACCORD (HR, 0.92; 95% CI, 0.79-1,08; P  = .32). Despite these overall neutral results, we continued to find evidence that fenofibratetherapy effectively reduced CVD in study participants with dyslipidemia, defined as triglyceride levels greater than 204 mg/dL and high-density lipoproteincholesterol levels less than 34 mg/dL (HR, 0.73; 95% CI, 0.56-0.95). Conclusions and Relevance Extended follow-up of ACCORD-lipid trial participants confirms the original neutral effect of fenofibratein the overall study cohort. The continued observation of heterogeneity of treatment response by baseline lipids suggests that fenofibratetherapy may reduce CVD in patients with diabetes with hypertriglyceridemiaand low high-density lipoproteincholesterol. A definitive trial of fibratetherapy in this patient population is needed to confirm these findings. Trial Registration clinicaltrials.gov Identifier:NCT00000620.