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Cox-2 inhibitors may interact with warfarin to substantially increase the risk of gastro-

intestinal bleeds.

A new study found the risk of taking cox-2s concomitantly with warfarin was around the same as with conventional NSAIDs, which were already known to interact with it.

GPs and researchers urged the use of gastroprotection with any NSAID, including a cox-2, if it had to be taken with warfarin.

Patients on warfarin were substantially more likely to be taking a conventional NSAID or a cox-2 if they were hospitalised with a GI bleed than if they had experienced no GI problems.

Hospitalised patients were 90 per cent more likely to be on conventional NSAIDs than those not hospitalised. They were 70 per cent more likely to be on celecoxib (Celebrex) and more than twice as likely to be on the now-withdrawn rofecoxib (Vioxx).

Study author Dr Marisa Battistella, of Toronto General Hospital in Canada, said: 'While the concomitant use of warfarin with NSAIDs is a recognised risk factor for GI haemorrhage, to our know-ledge our study is the first to examine the comparative safety of the cox-2 inhibitors celecoxib and rofecoxib in patients receiving warfarin.'

She said GPs should balance the risks and benefits of cox-2s in patients on warfarin and use proton pump inhibitors for gastroprotection.

Dr Battistella added that the study had shown no 'real difference' between NSAIDs and cox-2s in the extent of their interaction with warfarin.

Dr Richard Stevens, chair of the Primary Care Society for Gastroenterology and a GP in Oxford, said: 'The key message is that cox-2s are not

totally safe from a GI point of view. They are not quite as good as we thought they were in terms of GI protection.'

Dr Jamie Dalrymple, a GP with a special interest in gastroenterology in Norwich, said: 'The advice would be to use gastroprotection if a patient has a cox-2 inhibitor.'

Pfizer, manufacturer of Celebrex, said the study had not taken into account the fact that patients with high GI risk were often preferentially prescribed cox-2s.

The study of 98,821 elderly patients was published in the Archives of Internal Medicine.

Rofecoxib's 140,000 CHD toll

Two new studies provide contrasting pictures of the impact of use of cox-2 inhibitors on rates of cardiovascular disease.

Research in this week's Lancet suggests rofecoxib, which was withdrawn last September after being linked to heart problems, may have caused 140,000 cases of coronary heart disease in the USA since its launch in 1999.

Patients on the drug were 34 per cent more likely to develop coronary heart disease than those on other NSAIDs, according to the US Food and Drug Administration study.

But an observational study of 6,250 patients on cox-2s or non-naproxen NSAIDs found no significant difference in cardiovascular risk. The research, in the Archives of Internal Medicine, found a similar proportion of patients suffered at least one cardiovascular thrombotic event in the two groups.

By Nerys Hairon

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