Proton pump inhibitors (PPIs) administered in high doses and aspirin chemoprevention therapy additively improve health outcomes in patients with Barrett esophagus, according to research published in The Lancet.

A team of investigators in the United Kingdom conducted a randomized factorial design trial to determine the effectiveness of high-dose esomeprazole and aspirin on outcomes in patients with Barrett esophagus.

The researchers invited patients with Barrett esophagus ≥1 cm to be randomly but not blindly administered high-dose esomeprazole 40 mg twice daily or low-dose esomeprazole 20 mg once daily), with or without aspirin 300 mg once daily for ≥8 years.

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Primary outcomes included effectiveness of high-dose PPI vs low-dose PPI and the effectiveness of aspirin vs no aspirin. First occurrence of all-cause mortality, esophageal adenocarcinoma, or high-grade dysplasia was the primary combined end point.

The secondary outcome measured the impact of time on patient primary combined end points, cause-specific mortality, and combined end point factored by sex.

A total 2557 patients aged ≥18 years from 84 centers in the United Kingdom and 1 center in Canada were included in the analysis over a median of 8.9 years.  Recruitment of women was limited to approximately 20% of the total enrollment in light of the lower risk of Barrett esophagus in this population. High-dose esomeprazole without aspirin was administered to 705 individuals and low-dose esomeprazole without aspirin was administered to 705; 577 received high-dose esomeprazole with aspirin, and 571 received low-dose esomeprazole with aspirin. Participants in Canada were administered aspirin 325 mg/d, while those in the United Kingdom received 300 mg/d.

There were 313 reported primary event occurrences: 139 events in 1270 patients receiving high-dose PPI and 174 events in 1265 patients receiving low-dose PPI. No significant difference was seen with aspirin vs no aspirin (127 events in 1138 patients vs 154 events in 1142 patients). Time ratios (TR) for high- and low-dose esomeprazole and presence and absence of aspirin were 1.27 and 1.24, respectively.

In contrast, censoring patients who used other nonsteroidal anti-inflammatory drugs at initial use suggest aspirin is significantly better than no aspirin (TR, 1.29). The strongest effect was observed in patients taking high-dose esomeprazole in combination with aspirin compared with patients taking low-dose esomeprazole without aspirin (TR, 1.59).

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“We have shown that high-dose PPI use protects against a composite endpoint of all-cause mortality, oesophageal adenocarcinoma, and high-grade dysplasia,” noted the investigators. “These data also raise the possibility that all patients needing long-term PPI to control reflux symptoms might benefit from the co-prescription of aspirin with acid suppression. PPI could reduce the upper gastrointestinal bleeding associated with aspirin whilst the benefits of aspirin remain. This hypothesis should be investigated in large population-based trials.”

Disclosure: This study was funded by Cancer Research UK, AstraZeneca, the Wellcome Trust, and the Health Technology Assessment.


Jankowski JAZ, de Caestecker J, Love SB, et al. Esomeprazole and aspirin in Barrett’s oesophagus (AspECT): a randomised factorial trial [published online July 26, 2018]. Lancet. doi: 10.1016/s0140-6736(18)31388-6