A controlled trial found that in a high-risk patient population taking low-dose aspirin, a proton-pump inhibitor (PPI, pantoprazole) was more effective in reducing the risk of subsequent dyspeptic symptoms and bleeding than high dose treatment with a histamine H2-blocker (famotidine).

Gastro-intestinal adverse effects are frequent during treatment with low-dose aspirin, and a proportion of patients will have serious events such as gastro-intestinal bleeding and perforated peptic ulcer. PPI have been shown to be effective, however there is little evidence on the place of H2-blockers. This study compared high-dose famotidine (40mg twice daily) with pantoprazole 20mg daily in patients taking low-dose aspirin who had gastric erosion or peptic ulcer on endoscopy. Those with H. pylori infection were treated with standard triple therapy. Patients were randomised to famotidine or pantoprazole, with evening placebo in the pantoprazole group to maintain blinding, and followed up for 48 weeks. Primary endpoint was recurrent dyspeptic symptoms or bleeding ulcers/erosions.

Over the study period (Aug 2004 to Nov 2008), 237 potentially eligible patients were identified: of these, 161 were randomised to study treatment. One withdrew consent without taking any study drug and was excluded from further assessment. Of the 160 study patients, 130 (81.1%) completed the full 48 weeks, 65 in each group. There were more patients in the famotidine group who had a study endpoint compared to those in the pantoprazole group: 13 vs. 0 (20.0% vs. 0%; 95% one-sided CI for the risk difference, 0.1184 to 1.0; p<0.0001). Gastro-intestinal bleeding occurred in 7.7% vs. 0%; 95% one-sided CI for the risk difference, 0.0226 to 1.0; P= 0.0289); bleeding was considered major in one patient and life-threatening in one.

The authors conclude that in this study population, pantoprazole was significantly more effective in reducing the risk of recurrent dyspepsia or peptic ulceration / gastro-intestinal bleeding than high-dose famotidine. They discuss the limited previous research on the topic, and potential limitations of their study.

An accompanying editorial discusses the study, and compares the results with those of the recently published comparison of famotidine vs. placebo in patients taking low-dose aspirin (Lancet 2009; 374: 119–25). The author notes that the conclusion was not necessarily foregone and that the available research is limited. He compares the study results with that of the famotidine vs. placebo study, noting that this recruited lower-risk patients. Finally, he notes that other strategies for reducing NSAID-associated gastro-intestinal bleeding are in development, and that there are still questions needing answers before the optimum strategy can be determined.