The combination of aspirin and a high-dose proton-pump inhibitor (PPI) improves outcomes in patients with Barrett's esophagus, according to results of the The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial (AspECT) Barrett's esophagus is a premalignant condition that often precedes esophageal adenocarcinoma. Studies to date that have explored chemoprophylaxis with PPIs, aspirin, nonsteroidal anti-inflammatory agents, or statins to prevent progression of dysplasia and esophageal adenocarcinoma have yielded mixed results, Dr. Janusz Jankowski from Morecambe Bay University Hospitals, in Lancaster, U.K., and colleagues explain in The Lancet, online July 26. In the prospective AspECT trial, 2,557 patients with newly confirmed Barrett's esophagus were randomly assigned to receive high-dose (80 mg daily) or low-dose (20 mg daily) of the PPI esomeprazole, with or without aspirin (300 mg per day in the U.K., 325 mg per day in Canada) for at least eight years. Median follow-up and treatment duration was 8.9 years, for a total of 20,095 follow-up years of data. High-dose PPI therapy prolonged time to the composite endpoint of all-cause mortality, esophageal adenocarcinoma, and high-grade dysplasia in patients with Barrett's esophagus compared with low-dose PPI (time ratio, 1.27; 95% confidence interval, 1.01 to 1.58; P=0.038). Aspirin also had an effect on these endpoints, but this was only significant when patients who received NSAIDs were censored from the analysis. Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (time ratio, 1.59; 95% CI, 1.4 to 2.23; P=0.0068), the researchers report. "It seems likely that the use of aspirin and PPI would improve survival in Barrett's oesophagus if given for at least 9 years," they write. Clinically significant side-effects were rare. Only 1% of participants reported a study-treatment-related serious adverse event of grade 3 to 5, "with little increase in adverse events when adding aspirin to high-dose PPI," they note. Limitations of the study included a limited number of women and a predominantly white population. In a commentary published with the study, Dr. Frederik Hvid-Jensen from Aarhus University Hospital and Dr. Asbjoern Mohr Drewes from Aalborg University Hospital, both in Denmark, say more data are needed to confirm the benefits of aspirin plus a PPI "before this approach should be recommended as an additional chemopreventive measure." "Whether combination therapy should be offered for patients with Barrett's oesophagus, or even whether prophylactic treatment should be provided for patients with gastro-oesophageal reflux disease to prevent Barrett's oesophagus and reduce the risk of oesophageal adenocarcinoma, is still open for debate," they write. "Treatment with PPIs is related to increased gastrin levels, which have been shown to potentially increase the long-term risk of gastric cancers. However, the risk reduction and dose-response relationship for PPI in the AspECT trial are rather convincing and probably outweigh these considerations. Future guidelines should consider whether the notion of the lowest possible dose to control symptoms still applies and whether high-dose PPIs should be used as prophylaxis in Barrett's oesophagus." The study was funded by Cancer Research UK with a grant and esomeprazole tablets provided by AstraZeneca at no cost. Two authors have received grants from AstraZeneca. Source
