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Atorvastatin in Factorial with Omega-3 Fatty Acids Risk Reduction in Diabetes (Completed)



Overview

The main objectives are to determine:

  1. The proportion of people with Type 2 diabetes in community care who require LDL cholesterol lowering therapy by current guidelines.
  2. To what extent 20 mg per day atorvastatin can reduce estimated ten-year CHD risk to less than 15%.
  3. The effect of doubling the atorvastatin dose in those whose estimated ten-year CHD risk remains more than 20% after 16 weeks of therapy.
  4. To what extent 2 g per day omega-3 fatty acids can reduce triglyceride levels.
  5. Whether therapy adherence can be improved by the use of simple patient-centred techniques designed to help people take their medication on a regular basis.

Background

People with Type 2 diabetes (T2DM) have a two to four fold increased risk of coronary heart disease (CHD) compared with the general population. Although statin therapy to lower LDL cholesterol (LDL-C) has been shown to reduce CHD risk substantially in T2DM, it remains uncertain whether:

Using naturally occurring omega-3 polyunsaturated fatty acids could provide an alternative triglyceride lowering approach in T2DM, rather than adding a fibrate to statin therapy with the small potential risk of myositis or rhabdomyolysis. Patient's concerns about being on medication, and difficulties they have in taking tablets regularly, remain significant barriers to delivering the full benefits of evidence-based treatments. Little is known about detailed predictors of medication non-adherence and the impact of simple interventions to support medication taking.

Aims

This one-year trial, based in primary care, will evaluate:

  1. What proportion of people with Type 2 diabetes who are in community care require LDL-C lowering therapy by current guidelines?
  2. To what extent will a fixed dose of atorvastatin (20 mg per day) reduce estimated ten-year CHD risk to less than 15%?
  3. In those whose estimated ten-year CHD risk remains more than 20% after 16 weeks, what is the effect of doubling the atorvastatin dose?
  4. To what extent will a fixed dose of omega-3 fatty acids (2 g per day) reduce triglyceride levels?
  5. Can therapy adherence be improved by the use of simple patient-centred techniques designed to help people take their tablets on a regular basis?

Methods

1,000 patients from 70 UK practices will be randomised in a two-by-two factorial design comparing fixed doses of atorvastatin (Lipitor 20 mg per day) with placebo and, simultaneously, omega-3 fatty acids (Omacor 2 g per day) with a comparator (olive oil). Ten-year CHD risk will be estimated using the UKPDS Risk Engine at entry, at four months and at one year. Patients whose estimated CHD risk remains greater than 20% at four months will receive an additional tablet containing 20 mg atorvastatin whilst the remainder will receive an additional placebo tablet, in double-blind fashion. Study medication will be dispensed in containers which record time and date of use. These data, in combination with questionnaires, blood tests and tablet counts, will allow detailed evaluation of response to problems encountered in taking medication regularly. Half of the participating practices will be randomised to receive additional brief interventions to help support adherence with the medication regimen


Main Inclusion / Exclusion Criteria

Two-by-Two Factorial Randomisation

1000 patients
in total

Atorvastatin arm

Omega-3 fatty
acids arm
250
atorvastatin
omega-3 fatty acids
250
placebo
omega-3 fatty acids
250
atorvastatin
comparator (olive oil)
250
placebo
comparator (olive oil)

The factorial design makes for a more efficient study which allows for separate assessment of the atorvastatin and omega-3 fatty acid interventions, with minimal effects on non-drug study costs and sample size requirements.

Outcome measures

Primary (at four months)


Secondary

Trial Organisation

The AFORRD trial has been designed and developed by the University of Oxford Diabetes Trials Unit in an academic collaboration with Pfizer UK. The data arising from the trial will be owned, independently analysed and published by the Diabetes Trials Unit. The study has been possible due to sponsorship from Pfizer who will be responsible for some of the operational aspects of the trial, particularly with respect to regulatory issues, routine site monitoring and drug accountability.