Proton pump inhibitor use was associated with a greater than 75% reduction in the risk of neoplastic progression in Barrett’s esophagus.
Indeed, despite the "considerable costs" of these drugs, "prolonged PPI use is ... justified and feasible in Barrett’s patients and should be strongly recommended, in particular in guidelines," concluded Dr. Florine Kastelein in the April 1 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2012.11.014).
In what they called "the first methodological[ly] sound prospective study which shows that PPIs strongly reduce the risk of neoplastic progression in BE," Dr. Kastelein of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues looked at 540 patients with known or newly diagnosed endoscopic Barrett’s esophagus (BE) confirmed by intestinal metaplasia.
Patients had a median age of 60.5 years at inclusion and were followed for a median of 5.2 years; 71% were male.
All patients were recruited from multiple academic and regional hospitals across the Netherlands, and patients were excluded if they had Barrett’s esophagus shorter than 2 cm, prior antireflux surgery, or a history of high-grade dysplasia or esophageal adenocarcinoma.
Patients with neoplastic progression found within the first 9 months after study inclusion also were ultimately excluded "since high-grade dysplasia or esophageal adenocarcinoma may be missed at index endoscopy in these patients," the investigators said.
Surveillance was performed according to the guidelines of the American College of Gastroenterology, such that patients without dysplasia underwent gastroscopy with biopsy sampling every 3 years and patients with low-grade dysplasia underwent it every year.
Overall, at inclusion in the study, 462 (85%) patients had used a PPI for a median duration of 4.0 years.
Dr. Kastelien and her associates found that, during follow-up, 28 patients developed high-grade dysplasia and another 12 developed esophageal adenocarcinoma, for a combined annual incidence of 1.6%.
"PPI use at inclusion was associated with a reduced risk of neoplastic progression (hazard ratio, 0.43; 95% confidence interval: 0.21-0.88) and remained associated with a trend toward a protective effect after adjusting for age, gender, time of BE diagnosis, BE length, esophagitis histology, and use of other medications (HR, 0.47; 95% CI: 0.19-1.18)," the researchers wrote.
Moreover, among the 99% of patients who used a PPI at any time during follow-up (median, 5.1 years), time-dependent analysis revealed that PPI use was associated with a reduced risk of neoplastic progression (HR, 0.15; 95% CI: 0.06-0.40) and remained so after adjusting for age, gender, BE length, histology, baseline PPI use, and use of other medications (HR, 0.21; 95% CI: 0.07-0.66).
The authors found no significant difference between neoplastic progression and the various PPIs assessed in this study (including esomeprazole and pantoprazole as well as omeprazole, rabeprazole, and lansoprazole).
According to Dr. Kastelein and her associates, the study is actually limited by the incredibly high rate of compliance among its population.
"Despite the large sample size, only eight (2%) patients never used a PPI and 18 (3%) patients used a PPI during [only] a part of their follow-up period," they wrote.
"Although this reflects clinical practice in Western countries and is representative for a disease in which patients seek to avoid reflux symptoms, it limits the options for investigating the effect of PPIs," they added.
However, "because not all patients used PPIs throughout their entire follow-up period, we were able to perform time-dependent analyses."