Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

Diabetologia. 2009 Jan;52(1):50-9. doi: 10.1007/s00125-008-1179-5. Epub 2008 Nov 11.

Abstract

Aims/hypothesis: The aim of the study was to examine the impact of statin or omega-3-acid ethyl esters 90 (omega-3 EE90; omega-3-acid ethyl esters 90 refers to a mixture of ethyl esters of n-3 fatty acids) on estimated cardiovascular disease (CVD) risk in community-based people with type 2 diabetes but without known CVD and not taking lipid-lowering therapy.

Methods: A central computer randomised 800 patients in 59 UK general practices to atorvastatin (n = 401, 20 mg/day) or placebo (n = 399) and omega-3 EE90 (n = 397, 2 g/day) or placebo (n = 403) in a concealed factorial manner. Participants with LDL-cholesterol <2.6 mmol/l, triacylglycerol <1.5 mmol/l and estimated 10-year CVD risk <20% were compared at 4 months.

Results: Mean (SD) age was 63.5 (11.7) years, HbA(1c) 6.9 (1.1) % and known diabetes duration (median [interquartile range]) was 4 (2-8) years. Fifty-seven per cent were men, 90% white and 74% had an estimated 10-year CVD risk >or=20%. Of 732 patients with 4-month data, more allocated atorvastatin (n = 371) compared with placebo (n = 361) achieved LDL-cholesterol <2.6 mmol/l (91% vs 24%, p < 0.001) and had estimated 10-year CVD risks <20% (38% vs 26%, p < 0.001). No differences were seen between those allocated omega-3 EE90 (n = 371) compared with placebo (n = 361) for participants achieving triacylglycerol <1.5 mmol/l (65% vs 60%, p = 0.18) or estimated 10-year CVD risks <20% (34% vs 30%, p = 0.18). There were no side effects of note.

Conclusions/interpretation: Many community-based diabetic patients without known CVD remain at high CVD risk despite statin treatment and require additional risk-reduction strategies. The impact of omega-3 EE90 on CVD risk will remain uncertain until clinical endpoint trial results are available.

Trial registration: ISRCT no. 76737502.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Blood Pressure
  • Body Size
  • Cardiovascular Diseases / prevention & control
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / prevention & control
  • Female
  • Glycated Hemoglobin / analysis
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Patient Selection
  • Placebos
  • Pyrroles / therapeutic use*

Substances

  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Placebos
  • Pyrroles
  • Cholesterol
  • Atorvastatin

Associated data

  • ISRCTN/ISRCTN76737502