Cardiovascular safety of febuxostat.

Gout affects approximately 1 in 40 people and causes sudden flares of severe joint pain and swelling, most commonly affecting the big toe joint. Many people with gout experience recurrent flares. Gout is caused by high levels of urate in the blood, a waste product formed from normal chemical processes in the body. Long-term treatment of gout involves taking medication to lower urate levels, which reduces the risk of future flares.

Two medications are available to reduce urate levels: allopurinol and febuxostat. Allopurinol has been used for more than 50 years, however it is often given at too low a dose, or not at all, and around 1 in 20 people can’t take allopurinol due to side effects. An alternative drug, febuxostat was authorised for use in 2008, and is potentially more effective for the treatment of gout. However, early research studies suggested febuxostat may increase the risk of heart attacks and strokes. One subsequent large trial found that febuxostat may increase the risk of death from heart disease compared with allopurinol, while another did not. Current prescribing guidance in the UK states that febuxostat should not be given to people with pre-existing heart disease or strokes.

This study will use a database called the Clinical Practice Research Datalink (CPRD), which contains anonymised electronic health records of patients from thousands of general practices across the UK, as well as linked hospital and death records. It will identify and follow patients with gout, who are given either febuxostat, allopurinol or nothing to find out:

• is the risk of heart attacks and strokes greater when people start taking febuxostat for gout than when they take allopurinol or no treatment?
• are people who have had a heart attack or stroke in the past, or those who have a high risk of them, at greater risk of heart attacks or strokes when taking febuxostat than with allopurinol or no treatment?

If successful, this research will benefit patients and the NHS by:

• providing new evidence about the safety of febuxostat when taken to treat gout
• informing guidelines on safe and appropriate prescribing of febuxostat
• ensuring people with gout and heart disease can make an informed choice about taking febuxostat

We will involve patients in this research to help us to:

• design the study and interpret findings
• publicise the study findings widely in an easily understandable way
• help us understand an acceptable level of risk

We will promote our findings through Keele’s press office, our website and social media feeds, and our existing links to professional bodies and guideline developers (European and UK), to ensure dissemination to patients, health care professionals, and NHS commissioners and services.

Amount awarded: £81,805