Febuxostat in long-term gout treatment

Robert McLean, MD, is a rheumatologist and associate clinical professor of medicine at Yale School of Medicine, USA.

Should febuxostat be contraindicated in patients with cardiovascular disease? Can it be used as the drug of choice (instead of allopurinol) in long-term gout treatment?

Febuxostat came on the market about 15 years ago when it was realized that many people could not achieve adequate serum uric acid targets, which were felt to be around 6 mg/dL, I think, for people who have chronic gout. When febuxostat first came out, there was not as much data on allopurinol that it was safe in people who had chronic kidney disease (CKD), so people were very excited that we could use this new drug that was safer in kidney disease. And also it seemed to be a little bit more potent at higher doses.

However, over the years, some studies have suggested that maybe people who take febuxostat versus allopurinol have a slightly higher rate of cardiovascular outcomes. It’s really small when you look at the studies, but there are a couple meta-analyses that suggest that there’s a slightly higher cardiovascular risk. It’s really quite small, but there was enough suggestion that there was a difference that there are warnings now with febuxostat that if people have cardiovascular disease, you need to consider whether other agents are more appropriate. It’s not the first choice and it really shouldn’t be the first choice for anybody.

Allopurinol has been around longer. We know its safety profile well and it really should always be the first choice. If someone does not reach the target on allopurinol, or if in fact they’re allergic to allopurinol, I think febuxostat is perfectly appropriate. When looking at the guidelines and where febuxostat fits with people who have cardiovascular disease, it says that it’s conditionally okay but should be strongly considered to be used with low-dose aspirin or you just should have an appropriate conversation with the patient depending upon what their individual risks are. But it’s not an absolute contraindication.