title: Association of Fenofibrate Therapy With Long-term Cardiovascular Risk in Statin-Treated Patients With Type 2 Diabetes.
abstract: Patients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemia and low high-density lipoprotein cholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk.
  
  
  
  To determine whether fenofibrate reduces CVD risk in statin-treated patients with type 2 diabetes.
  
  
  
  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 lipoprotein levels less than 50 mg/dL (<55 mg/dL for women and African American individuals).
  
  
  
  Passive follow-up of study participants previously treated with fenofibrate or masked placebo.
  
  
  
  Occurrence of cardiovascular outcomes including primary composite outcome of fatal and nonfatal myocardial infarction and stroke in all participants and in prespecified subgroups.
  
  
  
  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 fenofibrate following completion of ACCORD. High-density lipoprotein and triglyceride values rapidly equalized among participants originally randomized to fenofibrate or 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 fenofibrate vs 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 fenofibrate therapy effectively reduced CVD in study participants with dyslipidemia, defined as triglyceride levels greater than 204 mg/dL and high-density lipoprotein cholesterol levels less than 34 mg/dL (HR, 0.73; 95% CI, 0.56-0.95).
  
  
  
  Extended follow-up of ACCORD-lipid trial participants confirms the original neutral effect of fenofibrate in the overall study cohort. The continued observation of heterogeneity of treatment response by baseline lipids suggests that fenofibrate therapy may reduce CVD in patients with diabetes with hypertriglyceridemia and low high-density lipoprotein cholesterol. A definitive trial of fibrate therapy in this patient population is needed to confirm these findings.
  
  
  
  clinicaltrials.gov Identifier: NCT00000620.
authors.affiliation: Memphis Veterans Affairs Medical Center and University of Tennessee Health Sciences Center, Memphis.
authors.forename: Marshall B
authors.initials: MB
authors.lastname: Elam
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
authors.affiliation: Wake Forest School of Medicine, Wake Forest, North Carolina.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Lovato
authors.affiliation: University of Washington, Seattle.
authors.forename: Marshall
authors.initials: M
authors.lastname: Corson
authors.affiliation: University of North Carolina, Chapel Hill.
authors.forename: Joseph
authors.initials: J
authors.lastname: Largay
authors.affiliation: Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Ontario, Canada.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez
authors.affiliation: HealthPartners Institute, Minneapolis, Minnesota.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: O'Connor
authors.affiliation: Atlanta Veterans Affairs Medical Center, Atlanta, Georgia.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Sweeney
authors.affiliation: Diabetes Endocrine Nutrition Group, Mentor, Ohio.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weiss
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: William T
authors.initials: WT
authors.lastname: Friedewald
authors.affiliation: University of North Carolina, Chapel Hill.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: McMaster Medical Center, Hamilton, Ontario, Canada.
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.affiliation: University of Washington, Seattle.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Probstfield
authors.affiliation: Berman Center for Outcomes and Clinical Research, Minneapolis, Minnesota.
authors.forename: Richard
authors.initials: R
authors.lastname: Grimm
authors.affiliation: Cleveland Veterans Affairs Medical Center, Cleveland, Ohio.
authors.forename: Faramarz
authors.initials: F
authors.lastname: Ismail-Beigi
authors.affiliation: Colorado School of Public Health, Aurora, Colorado.
authors.forename: David C
authors.initials: DC
authors.lastname: Goff
authors.affiliation: National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences, Bethesda, Maryland.
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Fleg
authors.affiliation: National Heart, Lung, and Blood Institute, Division of Cardiovascular Sciences, Bethesda, Maryland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Rosenberg
authors.affiliation: Wake Forest School of Medicine, Wake Forest, North Carolina.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Byington
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D011345:Fenofibrate