Jankowski JAZ, et al. - In patients with Barrett's esophagus, researchers assessed the effectiveness of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for outcome improvement. The findings from the present study suggested that high-dose PPI and aspirin chemoprevention therapy, particularly in combination, significantly and safely improved outcomes in patients with Barrett's esophagus.

Methods

• The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was performed at 84 centers in the UK and one in Canada.
• For this investigation, subjects with Barrett's esophagus of 1 cm or more were randomly allocated 1:1:1:1 via a computer-generated schedule to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada), unblinded, for at least 8 years.
• Reporting pathologists were masked to treatment allocation.
• In all patients in the intention-to-treat population, the primary composite endpoint was time to all-cause mortality, esophageal adenocarcinoma, or high-grade dysplasia, which was analyzed with accelerated failure time modelling adjusted for minimization factors like age, Barrett's esophagus length, intestinal metaplasia.

Results

• Two thousand, five hundred fifty-seven patients were selected between March 10, 2005, and March 1, 2009.
• Data showed 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin.
• Researchers observed that median follow-up and treatment duration was 8.9 years (IQR 8.2–9.8), and they assembled 20,095 follow-up years and 99.9% of planned data.
• They found 313 primary events.
• It was observed that high-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1.27, 95% CI 1.01–1.58, p=0.038).
• It was noted that aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1.24, 0.98–1.57, p=0.068).
• Aspirin was significantly superior to no aspirin (TR 1.29, 1.01–1.66, p=0.043; n=2236) if patients using non-steroidal anti-inflammatory drugs were censored at the time of first use.
• Data reported that combining high-dose PPI with aspirin had the strongest impact compared with low-dose PPI without aspirin (TR 1.59, 1.14–2.23, p=0.0068) and the numbers needed to treat were 34 for PPI and 43 for aspirin.
• According to the findings, only 28 (1%) participants reported study-treatment-related serious adverse events.