Glasgow, UK-The histamine H2-receptor antagonist famotidine (Pepcid, Johnson & Johnson/Merck), is effective in the prevention of peptic ulcers and erosive esophagitis in patients taking low-dose aspirin, a new study, Famotidine for the Prevention of Peptic Ulcers and Esophagitis in Patients Taking Low-Dose Aspirin (FAMOUS), has found [1].
Although proton-pump inhibitors (PPIs) are known to be effective in the treatment and prevention of ulcers related to aspirin, there have been concerns about their costs, safety, and risk of interaction with clopidogrel, which is frequently prescribed concurrently with aspirin, note Dr Ali S Taha (University of Glasgow, Scotland) and colleagues in their paper in the July 11, 2009 issue of the Lancet. Given these issues, famotidine represents a useful therapeutic alternative to PPIs for patients taking aspirin chronically for vascular protection, they say.
Gastroenterologist Dr Chris Hawkey (University Hospital, Nottingham, UK), who has written an editorial accompanying this study [2], told heartwire that this issue is important because up to 30% of the population are taking low-dose aspirin, "and they are at quite a high risk of a gastric bleed." And although from these study results "famotidine seems a good alternative to a PPI, the one thing this trial doesn't establish is which of these strategies is the most effective in preventing ulcers," he says. "That information is quite urgently needed if people are going to consider H2 antagonists like famotidine."
With regard to PPIs and their purported interaction with clopidogrel, he believes this is not a class effect: "Pantoprazole doesn't seem to interact, whereas omeprazole and esomeprazole do." And, he says, "Although no one has done a trial, you can probably handle this by taking one drug [PPI] in the morning and the other [clopidogrel] in the evening. So it's not such a big issue, but it is a genuine issue." This subject has recently been covered extensively in an article by heartwire.
Hawkey also has some interesting advice for cardiologists regarding continuing aspirin use in patients who do have bleeding ulcers on aspirin. "Everybody's instinct is to stop the aspirin, but what we know is that if people do stop the aspirin, they have a higher death rate, because they lose the protection on the heart and develop heart attacks and strokes." So he says, "Although it's counterintuitive, and the bleeding is worse if they stay on aspirin, we now recommend in gastroenterology that people should continue aspirin if they have a gastric bleed. So that makes it all the more important to protect them in advance with whatever strategy you choose."
80% reduction in gastric ulcers, esophagitis, with famotidine
FAMOUS is a phase 3, randomized, double-blind, placebo-controlled trial in patients from cardiovascular, cerebrovascular, and diabetes clinics at a UK hospital. Subjects were taking aspirin 75 to 325 mg per day with or without other cardioprotective drugs and had no ulcers or erosive esophagitis on endoscopy at baseline. They were randomized to receive famotidine 20 mg twice daily (n=204) or placebo twice daily (n=200).
The primary end point was the development of new ulcers in the stomach or duodenum or erosive esophagitis on final endoscopic examination at 12 weeks.
At this time point, gastric ulcers had developed in seven (3.4%) of the patients taking famotidine compared with 30 (15%) of those taking placebo (odds ratio 0.20, p=0.0002); duodenal ulcers were found in one (0.5%) patient on famotidine compared with 17 (8.5%) on placebo (OR 0.05, p=0.0045); and erosive esophagitis had developed in nine (4.4%) famotidine recipients compared with 38 (19%) of those taking placebo (OR 0.20, p<0.0001).
There were fewer adverse events in the famotidine group than in the placebo group (nine vs 15); four patients in the placebo group were admitted to the hospital with upper-gastrointestinal hemorrhage. The other most common adverse event was angina (affecting two patients taking famotidine and four on placebo). The researchers say they found no evidence of an interaction between famotidine and clopidogrel.
"Famotidine might be a useful alternative for PPIs in patients taking low-dose aspirin," Taha and colleagues conclude.
Is eradication of H pylori the way to go?
Another issue Hawkey addresses in his editorial is whether the eradication of Helicobacter pylori infection would be sufficient to prevent ulcer bleeding in aspirin users. "Nonsteroidal anti-inflammatory drugs [NSAIDs] cause ulcer bleeding by causing ulcers, no question about that," he said. "But aspirin may well cause bleeding, in at least some people, in ulcers that are formed for other reasons, such as H pylori."
"At the moment the evidence is mixed as to whether H pylori eradication is sufficient to protect people," he noted. But because people who have ulcer bleeds with coronary heart disease have more than a 10% mortality, it is imperative to establish whether or not H pylori eradication is effective, he says: "It's the key thing. If it has a bit of an effect but there is still risk, then it's no use as a strategy."
Hawkey himself is about to start a trial in 9000 patients to see whether eradicating H pylori infection before they begin aspirin therapy produces a clinically meaningful reduction in ulcer bleeds. In the meantime, "it's better to go with the belt-and-braces approach that we know," he concludes.
Sources
- Taha AS, McCloskey C, Prasad R, et al. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomized, double-blind, placebo-controlled trial. Lancet 2009; 374:119-125.
- Hawkey CJ. NSAIDS and aspirin: notorious or FAMOUS? Lancet 2009; 374:93-94.
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