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Dates: 2004 - To date
Funding: Pfizer
Collaborators: Diabetes Trial Unit (DTU), University of Oxford
Information: 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.