Chemoprevention in Barrett’s oesophagus

High-dose proton pump inhibitors (PPI) and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett’s oesophagus, according to the findings of a major trial in the area, the results of which were relayed to the ISG Winter Meeting by one of the study’s key authors.

Oesophageal adenocarcinoma is the sixth-most common cause of cancer death worldwide (five-year survival is less than 10 per cent), and is on the rise, with Barrett’s oesophagus the biggest risk factor.

As aspirin reduces inflammation and PPIs reduce acid reflux, the Aspirin and Esomeprazole Chemoprevention in Barrett’s metaplasia Trial (AspECT) aimed to evaluate the efficacy of high-dose esomeprazole PPI and aspirin for improving outcomes in patients with Barrett’s oesophagus, explained lead author Prof Janusz Jankowski, Senior Consultant Physician, University Hospitals Morecambe Bay, UK. 

AspECT is the first randomised trial to evaluate PPI and aspirin chemoprevention in Barrett’s oesophagus and the largest randomised trial of Barrett’s oesophagus ever done, with 20,095 participant-years of follow-up in 2,557 patients. The trial was carried out at 84 centres in the UK and one in Canada. Patients with Barrett’s oesophagus of 1cm or more were randomised 1:1:1:1 to receive high-dose (40mg twice-daily) or low-dose (20mg once-daily) PPI, with or without aspirin (300mg per day in the UK, 325mg per day in Canada) for at least eight years, in an unblinded manner.

The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia.

Between 2005 and 2009, patients were recruited and median follow-up and treatment duration was 8.9 years.

High-dose PPI (139 events in 1,270 patients) was superior to low-dose PPI (174 events in 1,265 patients).

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 per cent) participants reported study-treatment-related serious adverse events.

Further work is needed and the AspECT Excel Trial aims to provide longer-term answers.

Speaking to the Medical Independent, Prof Jankowski said the idea of a ‘magic bullet’ is never going to happen, and it is about balancing benefits and risks in an appropriate way.

“Do I think you should be on life-long PPIs without anyone ever reviewing you? Categorically not; that would be insane. What we are saying is that for people with significant symptoms of reflux disease, not only do they show efficacy, but we think that long-term PPI use, at least until nine years, is relatively safe. There may be a low incidence of side-effects but we haven’t seen that, though it could change with another five-to-10 years of follow-up.

“Secondly, the combination of low-dose aspirin with PPIs is remarkably safe and there is evidence of increased efficacy there” [in terms of preventing side-effects from sudden death and aspiration and bronchopneumonia].

“The third aspect, and the jury is still out, is whether low-dose aspirin can actually prevent cancer. We didn’t actually show any cancers being prevented, but we’ve seen the ‘smoking gun’ in the sense that low-dose aspirin particularly seemed to have an effect on the premalignant lesions of high-grade dysplasia and we are reasonably confident that if there had been follow-up for another five or 10 years, we’d be able to see that breakthrough in preventing oesophageal adenocarcinoma.”