Mortality study of 18 000 patients treated with omeprazole

Abstract

Background:The long term safety of potent gastric acid suppressive therapy has yet to be established. Method: General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993-1995. Death rates were compared with general population rates. Results: Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34-1.55); p<0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 (95% CI 1.58-2.08); p<0.0001), circulatory diseases (1.27 (95% CI 1.13-1.43); p<0.0001), and respiratory diseases (1.37 (95% CI 1.12-1.64); p<0.001). Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87-3.43); p<0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 (95% CI 2.60-6.04); p<0.0001), colon and rectum (1.40 (95% CI 0.84-2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19-2.19); p<0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20-10.09) (p<0.0001) in year 1; 2.88 (95% CI 1.62-4.79) (p<0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett's disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 (95% CI 2.17-4.80)). Six deaths occurred in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37-2.22)) and five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25-1.80)). No relationships were detected with numbers of omeprazole scripts received. Conclusions: Increases in mortality associated with treatment are due to pre-existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration.

Proton pump inhibitors and risk of gastric cancer: a population-based cohort study

“…Earlier studies of acid-suppressive drugs and gastric cancer have also reported an increased risk of gastric cancer associated with PPI use beyond the first year of treatment (Bateman et al, 2003;Garcia Rodriguez et al, 2006). In a cohort of 18 000 British PPI users, a sevenfold increased risk of death from gastric cancer was found, which disappeared by the fourth year of follow-up, indicating that this was because of confounding by indication rather than a causal relationship with PPI use (Bateman et al, 2003).…”

“…In a cohort of 18 000 British PPI users, a sevenfold increased risk of death from gastric cancer was found, which disappeared by the fourth year of follow-up, indicating that this was because of confounding by indication rather than a causal relationship with PPI use (Bateman et al, 2003). A recent case -control study, based on the General Practice Research Database, reported that current PPI users with more than 3 years of use experienced a threefold increased risk (OR 3.0, 95% CI: 1.0 -9.0) of non-cardia gastric cancer, whereas current longterm users of H2RA had no excess risk (OR 0.9, 95% CI: 0.5 -1.8) (Garcia Rodriguez et al, 2006).…”

“…Two studies based on UK populations reported an increased risk of gastric cancer among users of PPI that was attributed to probable reverse causation or confounding by indication (Bateman et al, 2003;Garcia Rodriguez et al, 2006). Given the widespread use of PPI and the unresolved questions about their carcinogenic potential, we examined the association between PPI use and the risk of gastric cancer in a large population-based cohort of Danish PPI users.…”

Inflammation, atrophy, and gastric cancer

“…PPIs are one of the most commonly prescribed drugs and are generally perceived by most physicians as very effective and relatively safe. Indeed, in the largest mortality study, of 18,000 patients treated with omeprazole, there was no increased mortality that was not associated with preexisting illness (96). However, only 25% of the patients studied were on long-term therapy, and the length of follow-up might have been insufficient to detect an increase in gastric cancer.…”

Efeitos de drogas inibidoras da secreção ácida do estômago sobre as respostas hipotensoras do nitrito de sódio

“…Entretanto estudos recentes sugerem que o omeprazol afeta negativamente a função vascular, aumentando o risco de infarto agudo do miocárdio o que tem sido relacionado, pelo menos em parte, à atividade reduzida do NO (Bateman et al 2003;Shih et al 2014;Shah et al 2015).…”