Famotidine reduces peptic ulcer risk in patients receiving low-dose aspirin
A controlled trial found that over the short-term, famotidine, a histamine-H2 receptor blocker, was effective in reducing new gastric and duodenal ulceration in patients taking low-dose aspirin.
The incidence of upper-gastrointestinal complications associated with low-dose aspirin has increased along with its wider use, however there is debate over the most effective prophylaxis because effective drugs and clinical trials are few. Proton-pump inhibitors (PPI) are widely used, but may be costly and recent studies suggest a possible adverse interaction between PPI and clopidogrel – often co-prescribed with aspirin. The authors of this study aimed to determine whether a histamine-H2 blocker, famotidine, was effective in reducing peptic ulceration and erosive oesophagitis in patients taking low-does aspirin.
Participants were adult patients of the cardiovascular, cerebrovascular, and diabetes clinics of one UK hospital, who were eligible for low-dose aspirin treatment that was likely to last at least 12 weeks (the intended study duration). Other anti-platelet treatment was not a criterion for exclusion.
Potential study patients had a baseline endoscopy and those with active serious upper gastro-intestinal disease excluded: those eligible were randomised to receive famotidine 20mg twice daily or matching placebo. They had a further endoscopy at 12 weeks after randomisation, and the primary outcome was development of new peptic ulcers or erosive oesophagitis at this point.
The study was stopped early before the planned full recruitment (700 patients) because interim analysis indicated overwhelming evidence of benefit. At this point, 14,515 had been assessed for eligibility and 404 randomised (famotidine n=204, placebo n=200). The main reason for exclusion was ineligibility (n=9,085). There were 90 withdrawals (famotidine n=37, placebo n=53), the most common reasons being withdrawal of consent (n=29) and loss to follow-up (n=17).
In the intention to treat analysis, peptic ulcers and erosive oesophagitis were less frequent in the famotidine group compared to the placebo group: any endpoint component developed in 5.4% vs. 32.5%, with an odds ratio (OR) of 0.12 (95% CI, 0.06 to 0.23; p<0.0001).
In terms of individual components, gastric ulcers were found in 3.4% vs. 15.0% (OR, 0.20; 95% CI, 0.09 to 0.47; p=0.0002), duodenal ulcers in 0.5% vs. 8.5% (OR 0.05%; 95% CI, 0.01 to 0.40; p=0.0045), and erosive oesophagitis in 4.4% vs. 19.0% (OR, 0.20; 95% CI, 0.09 to 0.42; p<0.0001). There were 24 reported adverse events (famotidine n=9, placebo n=15), none of which were considered to be related to the study treatment. There was no indication of any interaction with clopidogrel, nor were patients taking famotidine more likely to have a cardiac event.
The authors conclude that famotidine is effective in prevention of peptic ulcers and erosive oesophagitis in patients taking low-dose aspirin. It may therefore offer an alternative option to PPI in such patients.
An accompanying Comment discusses the study, including the observation that famotidine was more effective in patients with H. pylori infection.
The incidence of upper-gastrointestinal complications associated with low-dose aspirin has increased along with its wider use, however there is debate over the most effective prophylaxis because effective drugs and clinical trials are few. Proton-pump inhibitors (PPI) are widely used, but may be costly and recent studies suggest a possible adverse interaction between PPI and clopidogrel – often co-prescribed with aspirin. The authors of this study aimed to determine whether a histamine-H2 blocker, famotidine, was effective in reducing peptic ulceration and erosive oesophagitis in patients taking low-does aspirin.
Participants were adult patients of the cardiovascular, cerebrovascular, and diabetes clinics of one UK hospital, who were eligible for low-dose aspirin treatment that was likely to last at least 12 weeks (the intended study duration). Other anti-platelet treatment was not a criterion for exclusion.
Potential study patients had a baseline endoscopy and those with active serious upper gastro-intestinal disease excluded: those eligible were randomised to receive famotidine 20mg twice daily or matching placebo. They had a further endoscopy at 12 weeks after randomisation, and the primary outcome was development of new peptic ulcers or erosive oesophagitis at this point.
The study was stopped early before the planned full recruitment (700 patients) because interim analysis indicated overwhelming evidence of benefit. At this point, 14,515 had been assessed for eligibility and 404 randomised (famotidine n=204, placebo n=200). The main reason for exclusion was ineligibility (n=9,085). There were 90 withdrawals (famotidine n=37, placebo n=53), the most common reasons being withdrawal of consent (n=29) and loss to follow-up (n=17).
In the intention to treat analysis, peptic ulcers and erosive oesophagitis were less frequent in the famotidine group compared to the placebo group: any endpoint component developed in 5.4% vs. 32.5%, with an odds ratio (OR) of 0.12 (95% CI, 0.06 to 0.23; p<0.0001).
In terms of individual components, gastric ulcers were found in 3.4% vs. 15.0% (OR, 0.20; 95% CI, 0.09 to 0.47; p=0.0002), duodenal ulcers in 0.5% vs. 8.5% (OR 0.05%; 95% CI, 0.01 to 0.40; p=0.0045), and erosive oesophagitis in 4.4% vs. 19.0% (OR, 0.20; 95% CI, 0.09 to 0.42; p<0.0001). There were 24 reported adverse events (famotidine n=9, placebo n=15), none of which were considered to be related to the study treatment. There was no indication of any interaction with clopidogrel, nor were patients taking famotidine more likely to have a cardiac event.
The authors conclude that famotidine is effective in prevention of peptic ulcers and erosive oesophagitis in patients taking low-dose aspirin. It may therefore offer an alternative option to PPI in such patients.
An accompanying Comment discusses the study, including the observation that famotidine was more effective in patients with H. pylori infection.
Lancet, published early online 6 July 2009; doi:10.1016/S0140-6736(09)61246-0 (link to abstract); Lancet, published early online 6 July 2009; doi:10.1016/S0140-6736(09)61245-9 (Comment, link to full text; subscription required for access)
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