Helicobacter pylori eradication and aspirin: a puzzle yet to be solved

We read with great interest the Article by Chris Hawkey and colleagues1 on the Helicobacter Eradication Aspirin Trial (HEAT). The authors should be commended for performing such a complex trial. Although the trial was conceived to evaluate the role of Helicobacter pylori eradication in older patients (aged ≥60 years) prescribed aspirin, the study was not planned to verify eradication. A breath retest was randomly performed in only 10% of patients, reporting H pylori eradication in 146 (90·7%) of 161 patients receiving active eradication therapy. Such high eradication is usually achieved only with quadruple therapies lasting 10 days or longer, but not with 7-day triple therapies.2, 3 Furthermore, H pylori eradication was unexpectedly observed in 41 (24·0%) of 171 patients in the placebo group. Although exposure to clarithromycin, which occurred in 13 (32%) of the 41 control patients with a negative repeat breath test, might theoretically support these results,4 there is no clear explanation for the remaining cases. These findings suggest that it would have been worthwhile to assess eradication in a new larger random sample in both groups. During the first 2·5 years of follow-up, prescriptions for aspirin decreased progressively in both study groups, while prescriptions for proton pump inhibitors increased in both groups. Even if analyses were adjusted for time-varying prescribed medications, this trend might have had consequences on the second part of follow-up with regard to the primary outcome, and a type two error cannot be excluded. HEAT is an important study showing that H pylori eradication confers some benefits in the primary prevention of ulcer bleeding. However, future trials should evaluate H pylori eradication in all enrolled patients, and adopt more rigorous criteria on the use of proton pump inhibitors to better clarify the effect of eradication on aspirin-associated ulcer bleeding.