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942
STOMACH
Mortality study of 18 000 patients treated with
omeprazole
D N Bateman, D Colin-Jones, S Hartz, M Langman, R F Logan, J Mant, M Murphy,
K R Paterson, R Rowsell, S Thomas, M Vessey, for the SURVEIL (Study of Undetected
Reactions. Vigilance Enquiry into Links) Group
Gut 2003;52:942-946
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.
See end of article for
authors’ affiliations
Correspondence to:
Professor M J S Langman,
Department of Medicine,
Queen Elizabeth Hospital,
Birmingham B15 2TH, UK;
M.J.S.Langman
@bham.ac.uk
Accepted for publication:
20 February 2002
Results: Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received fur-
ther 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, includ-
ing pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesopha-
geal adenocarcinoma in those without oesophageal mucosal damage recorded at registration.
The introduction of any new class of drugs, such as the
proton pump inhibitors (PPIs), where usage is likely to be
widespread and prolonged, requires that safety during
chronic treatment is assured. The need for such assessment is
emphasised by claims that omeprazole treatment might
adversely affect the management of upper gastrointestinal
cancer because amelioration of symptoms and re-
epithelialisation of the cancer might be promoted, so hinder-
ing disease recognition.1 It has also been suggested that raised
serum gastrin concentrations in response to reduced acidity
might act as growth promoters,2 or that treatment might
accelerate the onset of atrophic gastritis, so predisposing to
gastric cancer.3 Moreover, as omeprazole is commonly used to
treat gastro-oesophageal reflux disease, it is important to
determine whether treatment influences the frequency of
oesophageal adenocarcinoma, a tumour known to complicate
oesophageal metaplasia (Barrett’s disease), which occurs in
association with oesophageal reflux associated damage.
We examined mortality rates from any cause over a four
year period during or after treatment with omeprazole in six
cities in England and Scotland. Death rates were compared
with those expected nationally. Data have strength in relating
risks to those observed in the general population, as done pre-
viously by us for cimetidine.4-6
METHOD
We sought to register a cohort of 18 000 patients prescribed
omeprazole in the six UK conurbations of or surrounding Bir-
mingham, Glasgow, Newcastle, Nottingham, Oxford, and
Portsmouth. Using the computerised registers of cooperating
general practitioners, we identified takers of omeprazole in the
period 1993-1995. Records of patients who were still alive and
who had received at least one prescription for omeprazole
were examined and details taken of, inter alia, the patient’s
age, sex, and NHS number, prescription data, and the reasons
for any prescription, together with details of any prior diagno-
sis of malignant disease, any previous upper abdominal surgi-
cal procedures, and any other recorded antisecretory drug use
in the previous 12 months. We excluded from consideration all
those dying prior to the registration date.
Clinical diagnoses were those recorded in individual case
notes and were not re- interpreted, but details of investiga-
tions were recorded. Individual diagnoses of ulcer, oesoph-
agitis, Barrett’s oesophagus, hiatal hernia or reflux, and cancer
required specific mention of these following investigation.
Abbreviations: O/E, observed/expected; PPI, proton pump inhibitor;
NHSCR, National Health Service Central Register; ICD, International
Classification of Disease.
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