There are many patients worldwide on low-dose aspirin for a variety of conditions, yet few treatments available to treat the damage that can be caused to the lining of the stomach and upper intestine that can be caused by this damage. The FAMOUS trial, reported in an Article Online First and in an upcoming edition of The Lancet, shows that famotidine is effective in the prevention of stomach and upper intestinal ulcers, and damage to the gullet.
Low-dose aspirin (75mg-325mg) is one of the most widely used drugs in the world. Increasingly, it is being bought over the counter or prescribed for its anti-clotting activity in the heart and brain, and in patients with diabetes. Despite the benefits of aspirin use, its rise has been accompanied by a rise in gastrointestinal complications, such as peptic ulcer bleeding, perforation, and sometimes death. Proton-pump inhibitors (PPIs), such as omeprazole and Lansoprazole, can prevent such ulcers but there have been concerns about cost, safety, and risk of interaction with clopidogrel, another anti-clotting drug which is often prescribed with aspirin. In this phase III randomised, controlled trial (the FAMOUS study), Dr Ali S Taha, Crosshouse Hospital, Kilmarnock, UK and University of Glasgow, UK, and colleagues studied the effect famotidine, which has a different mechanism of action to proton-pump inhibitors and belongs to a group of drugs called H2-receptor antagonists. (is it possible to provide a lay explanation of different mechanisms of action?) It lowers acidity by binding to the histamine particles in the stomach, and is broken down by different enzymes in the liver. This explains its gentler action compared with proton-pump inhibitors, particularly in patients requiring the other anti-clotting drug, clopidogrel.
Adult patients from Crosshouse Hospital were eligible for the study if they were taking aspirin 75mg-325mg per day with or without cardioprotective drugs. Patients were given famotidine 20mg twice daily (204 patients) or placebo twice daily (200 patients). They were then given an endoscopic examination at 12 weeks.
The researchers found that stomach ulcers had developed in 3% of patients given famotidine compared with 15% given placebo. Upper-intestinal or duodenal ulcers were found in just one patient (0.5%) in the famotidine group compared with 17% of those given placebo. Gullet ulcers occurred in 4% of famotidine patients compared with 19% of placebo patients. There were fewer adverse events in the famotidine group (9 vs 15 placebo).
The authors conclude: "Famotidine is effective in the prevention of gastric and duodenal ulcers, and erosive oesophagitis in patients taking low-dose aspirin."
They add*: "There is little doubt that aspirin and other anti-clotting drugs are very useful in the prevention of heart, brain, and other vascular diseases, hence their increasing use world-wide. Patients on such drugs should continue using them as advised by their family doctors or hospital specialists. However, everybody should be aware that aspirin use can also be associated with a variety of gastrointestinal or digestive system problems, which sometimes can be serious. The results of this research widen the options for the prevention of such problems particularly when more than one clotting drug is required."
In an accompanying Comment, Dr Chris Hawkey, Nottingham Digestive Diseases Centre, University Hospital, Nottingham, UK, says: "Whilst NSAIDs cause ulcers that then bleed, aspirin may provokes bleeding from ulcers that arose by other means, principally H.pylori infection. Some, but not all, evidence suggests that H. pylori eradication may be sufficient to prevent ulcer bleeding in aspirin users. This simple manoeuvre is an important question that merits answer through an outcome study since there is the potential to make aspirin use safer. In the meantime, famotidine seems a good alternative to a PPI."
Dr Ali S Taha, Crosshouse Hosptial, Kilmarnock, UK and University of Glasgow, UK T) +44 (0) 1563 52 11 33 / +44 (0) 1563 82 72 80
E) ali.taha1@btinternet.com
Dr Chris Hawkey Nottingham Digestive Diseases Centre, University Hospital, Nottingham,UK T) +44 (0) 115 823 1033
E) Cj.hawkey@nottingham.ac.uk
For full Article and Comment, see: http://press.thelancet.com/famousstudy.pdf
Note to editors: *Quote direct from Dr Taha and not found in text of Article
Journal
The Lancet