Table 2.
Summary of clinical studies associating of gastric pre-malignant conditions with long-term use of proton pump inhibitors
| Author, year | Study design, country | Source of database | No. of PPI and control group | Information of PPI | Aims | Main outcomes |
| Kuipers et al[34], 1996 | Prospective cohort, Netherland/ Sweden | Reflux esophagitis cohort (fundoplication/ omeprazole) | 105 (PPI)/ 72 (fundoplication) | Type (omeprazole only), dose (20 and 40mg), duration (5 years) | Corpus gastritis, atrophic gastritis | Atrophic gastritis: 0/31 (fundoplication group) vs 18/59 (omeprazole group) with H. pylori infection at baseline (P < 0.001); 0/41 (fundoplication group) vs 2/46 (omeprazole group) without H. pylori infection at baseline (P = 0.62) |
| Lundell et al[35], 1999 | RCT, Sweden | RCT comparing the efficacy of omeprazole and ARS | 155 (PPI)/155 (ARS) | Type (omeprazole only), duration (3 years) | Gastric corpus glandular atrophy, intestinal metaplasia of corpus mucosa | No difference in glandular atrophy between H. pylori-infected omeprazole and ARS group (P = 0.57); No difference in intestinal metaplasia between H. pylori-infected omeprazole and ARS group. |
| Lundell et al[36], 2006 | RCT, Sweden | RCT comparing the efficacy of omeprazole and ARS | 117 (PPI)/98 (surgical arm) | Type (omeprazole only), duration (7 years) | Gastric corpus glandular atrophy | No significant change of gastric atrophy between H. pylori-negative omeprazole and ARS group; Two patients developed severe atrophy from none at baseline in H. pylori-infected omeprazole group, three patients developed mild atrophy from none at baseline in H. pylori-infected ARS group, no statistical difference. |
| Gental et al[37], 2003 | Two RCTs, United States | Maintenance trial (n = 519), Safety trial (n = 807) | Maintenance trial: 519 (PPI)/169 (placebo); Safety trial: 807/PPI | Type (esomeprazole only), duration (6 months: maintenance trial; 12 months: safety trial) | Atrophy (antrum and corpus), intestinal metaplasia (antrum and corpus) | In the maintenance studies, the majority of omeprazole group had no change in the extent of atrophy and intestinal metaplasia. In the safety study, > 98% of omeprazole had either no change or improved atrophy scores in antrum and corpus, and intestinal metaplasia scores remained unchanged or improved compared with those that worsened. |
PPI: Proton pump inhibitor; RCT: Randomized controlled trial; ARS: Anti-reflux surgery; H. pylori: Helicobacter pylori.