AFORRD: Atorvastatin and fish oil in diabetes
|Dates:||2004 - Ongoing|
|Collaborators:||Diabetes Trial Unit (DTU), University of Oxford|
Alastair Gray, Helen Dakin
AFORRD is a multicentre, randomised, double-blind placebo-controlled trial evaluating the impact of Atorvastatin in a Factorial design with Omega-3 fatty acids on cardiovascular Risk Reduction in patients with Type 2 Diabetes.
The trial recruited patients who were being treated for type 2 diabetes in general practice but who had no known cardiovascular disease (CVD) and who were not taking lipid-lowering medication.
The trial used a 2x2 factorial design, by which patients were randomised to receive:
• atorvastatin (20 mg/day) plus omega-3-acid ethyl esters 90 (which includes a mixture of ethyl esters of n-3 fatty acids derived from fish oil);
• atorvastatin alone (plus omega-3 placebo);
• omega-3-acid ethyl esters alone (plus atorvastatin placebo); or
• placebos for both omega-3 and atorvastatin
Those patients whose estimated 10-year risk of coronary heart disease was greater than 20% based on outcomes at 16 weeks received an additional tablet of 20 mg atorvastatin for the remainder of the one-year study period, while the remainder received an additional placebo tablet.
In addition to evaluating atorvastatin and omega-3 fatty acids, the study also evaluated interventions designed increase compliance, which were implemented at half of the participating centres.
A total of 800 patients were recruited from 59 GP practices across the UK. Patient follow-up was completed in late 2006.
The primary outcomes comprised the proportion of patients with LDL levels <2.6 mmol/L (<100 mg/dL) at 16 weeks and the proportion with triglycerides <1.5 mmol/L (<200 mg/dL) at 16 weeks. The EuroQol EQ-5D and the Medical Outcomes Study Short-Form 12-Item Health Survey (SF-12) were also administered to all patients at baseline and at 12 months. Data were collected on healthcare resource use, including: study medication, concomitant medications, community healthcare contacts and inpatient admissions.
Sixteen-week clinical results have recently been published in Diabetologia and show that:
• Significantly more patients allocated to 20 mg/day atorvastatin achieved LDL cholesterol <2.6 mmol/L at week 16 compared with those receiving placebo (91% vs 24%, p<0.001).
• Atorvastatin also significantly increased the proportion of patients with an estimated 10-year risk of CVD <20% (38% vs 26%, p<0.001).
• However, omega-3 fatty acids had no significant effect on triglyceride levels or estimated 10-year CVD risk (p=0.18).
• A high proportion of diabetic patients managed in the community remained at high CVD risk despite statin treatment.
Analysis of the 16-week clinical results is ongoing. HERC members are in the process of conducting the economic evaluation of the trial, which will extrapolate the number of life-years and quality adjusted life years (QALYs) gained through treatment over a lifetime using the UKPDS Diabetes Outcomes Model.
Related Publication: Holman, R. R., S. Paul, et al. (2009). "Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial." Diabetologia 52(1): 50-9.