Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial

Abstract

SummaryBackgroundOesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.MethodsThe Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit 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) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FindingsBetween March 10, 2005, and March 1, 2009, 2557 patients were recruited. 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. Median follow-up and treatment duration was 8·9 years (IQR 8·2–9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. 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). 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). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01–1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14–2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.InterpretationHigh-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FundingCancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

Editorial: less acid, less cancer? Is this the question? Authors’ reply

“…Indeed, a recent publication from the Aspirin Esomeprazole Chemoprevention Trial (AsPECT) provides the best data to date. That study showed that high‐dose PPI, especially when taken with aspirin, reduces the risk of neoplastic progression and mortality in patients with Barrett's oesophagus …”

The Rationale and Efficacy of Primary and Secondary Prevention in Adenocarcinomas of the Upper Gastrointestinal Tract

“…A nested case-control study in more than 1,000 US Veterans confirmed this effect, which was even more obvious with higher doses of PPI (OR 0.11; 95% CI 0.04-0.36) [14]. Recently, the effect of PPI on the prevention of further progression of BO has been prospectively assessed in the AspECT trial [15]. A total of 2,557 patients were recruited in 84 UK centres and one in Canada before randomisation in a 2-by-2 factorial design to assess the long-term effect of Esomeprazole (20 vs. 40 mg) each with or without Aspirin (300 mg).…”

“…The use of Aspirin was beneficial only when patients with the use of further NSAIDs at inclusion were censored. The combination of high dose PPI plus Aspirin showed the best outcome regarding chemoprevention of BO and the complications mentioned above as included in the composite primary endpoint [15]. The number needed to treat to prevent a primary event was 34 for PPI and 43 for Aspirin.…”

Prevention of gastric cancer by Helicobacter pylori eradication: A review from Japan

“…The prevention effect on gastric cancer was more prominent in those who used aspirin daily or for 5 or more years. Furthermore, it has been reported that PPIs and aspirin combination therapy may prevent esophageal adenocarcinoma in Barrett's eosophagus . Concerning the relationship between aspirin and events of gastrointestinal bleeding, Garcia Rodriguez et al reported that concomitant use of PPIs and aspirin decreased upper gastrointestinal bleeding risks relative to aspirin monotherapy .…”