Jankowski J, et al. - Authors assessed the effectiveness of aspirin and high dose acid suppression for preventing esophageal adenocarcinoma (EA) in patients with Barrett’s esophagus (BE). In BE patients, this is the largest randomized controlled chemoprevention trial. A significant reduction in rates of death, EA or high-grade dysplasia (HGD) incidence was noted with high dose proton pump inhibitors (PPI) and aspirin chemoprevention therapy, especially in combination. This therapy was deemed to be safe.

Methods

• Researchers recruited patients with ≥ 1cm of BE and no HGD or EA at baseline in UK and Canadian hospitals.
• Patients were randomized by a central trials unit using a computer-generated schedule to hide distribution.
• They randomized the patients unblinded 1:1:1:1 in a 2X2 factorial design to high dose (40mg twice daily) or low dose (20mg once daily) esomeprazole PPI acid suppression, alone or in combination with low dose aspirin 300mg/day (330mg in Canada).
• Time to all-cause mortality or EA or HGD was the composite primary endpoint, analyzed using accelerated failure time modelling adjusting for minimization factors (age, length of Barrett’s esophagus and presence of intestinal metaplasia).

Results

• Experts recruited 2,563 BE patients, who were followed-up for a median of 8.9 years (interquartile range 8.2-9.8) with 20,095 years of follow up.
• Results demonstrated 313 events of the composite primary endpoint.
• As per data, a statistically significant superiority of high dose PPI to low dose PPI was noted (p=0.037, N = 2,535, time ratio (TR) 1.27, 95% CI = 1.01-1.58).
• A trend to benefit was demonstrated by the aspirin therapy, but it was not statistically significant (p=0.068, N = 2,280, TR = 1.24, 95% CI = 0.98 – 1.57).
• The strongest effect was noted with the combination of aspirin with high dose PPI vs low dose PPI with no aspirin (TR = 1.59, 95% CI = 1.14 to 2.23, p=0.007).
• Results demonstrated that there were few serious adverse events reported (1.0% of patients), with 99.9% data collected.