G E R I AT R I C T H E R A P E U T I C S

Editors: Dr Michael Woodward, Director of Aged Care Services, Dr Margaret Bird, Consultant Geriatrician,
Ms Sarah McKernin, Clinical Pharmacist, Austin & Repatriation Medical Centre, Vic.; Ms Helen Lourens,
Director of Pharmacy, Coffs Harbour Hospital, NSW; Mrs Robyn Saunders, Clinical Services Consultant,
Slade Pharmacy, Vic.

Management of Peptic Ulcer Disease

in Older People
Gregory J Lockrey

ABSTRACT

more common in patients diagnosed with gastric ulcer, and in those presenting with bleeding ulcers (gastric or duodenal).1 Various authors have reported that
the incidence of both gastropathy (ulcers or erosions)
and death is 3 to 10 times higher in NSAID users
than in non-users. In two large studies of NSAID
users, the prevalence of ulcer disease was around 20
to 30%. Gastric ulcers were twice as common as
duodenal.2,3

INTRODUCTION
Peptic ulcer disease has its greatest impact on older
people. The principal aetiological factors use of
aspirin or non-steroidal anti-inflammatory drugs, and
Helicobacter pylori infection are more common in
those aged over 60. Add to that a greater prevalence
of cardiovascular and respiratory disease, and it is
not surprising that the morbidity and mortality of
ulcer disease are highest in the elderly. The actual
management of ulcer disease changes little with the
age of an individual patient. But improved management of peptic ulcers, and their complications, should
be a priority in the older age groups, whose members have much to gain.

Helicobacter pylori
In Australia, the organism H. pylori infects approximately 38% of Anglo-Celtic adults. Prevalence increases with age, from 18% of 20-30-year-olds to
53% of those aged over 70. The organism is probably acquired in childhood, yet its associated diseases mostly present in adult life. Infection rates are
falling as living standards improve; high prevalence
rates in older persons reflect the infection rate when
they were children. This infection is more common
in men, smokers, and those with lower incomes.4
Rates of infection are higher in some population
groups. Over 95% of duodenal ulcers and 65-70%
of gastric ulcers are H. pylori positive.5 Eradication
of infection has been shown to alter the otherwise
chronic, relapsing nature of peptic ulcer disease; reinfection is an uncommon event.6
H. pylori infection can be diagnosed by a variety
of methods (Table 1).The particular method selected
in any individual will depend on whether ulcer disease has already been diagnosed, or ulcer healing
needs to be checked. It is important to remember

Peptic ulcer disease is common in older people, and

they bear much of the impact of its complications.
Improved understanding of the principal causes of ulcers Helicobacter pylori and non-steroidal anti-inflammatory drugs has recently led to significant advances
in drug treatment for ulcer disease. These new treatments offer the prospect of better symptom relief and
improved mortality in the elderly.
Aust J Hosp Pharm 1999; 29: 45-50.

AETIOLOGY
Non-Steroidal Anti-Inflammatory Drugs
(NSAIDs)
NSAID use by the elderly population is increasing
steadily. Close to half of all such drugs are used by
those aged over 60; approximately 15% of persons
over 60 take NSAIDs.1 Aspirin or NSAID use is
Gregory J Lockrey, MB BS (Melb), MPH, FRACP
Gastroenterology Unit
Austin & Repatriation Medical Centre
Heidelberg, Victoria

Address for correspondence:

Dr Gregory Lockrey
Austin Private Consulting Suite
226 Burgundy Street, Heidelberg Vic. 3084
E-mail: lockgj@internex.net.au

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45

Table 1. Methods of diagnosing Helicobacter pylori infection

Test

Advantages

Disadvantages

Endoscopic
(invasive)

Urease testing
Histology
Culture

Fast, accurate, cheap

Detects other diagnoses
Detects drug resistance

Expensive
Slow, difficult, expensive

Breath test
(non-invasive)

14
13

Accessible, accurate
Accurate, simple, no radiation,
'gold standard'

Radiation use
Limited availability

Blood test
(non-invasive)

Serology

Simple

Variability, cannot assess eradication

C-urea
C-urea

that both endoscopic and breath tests for H. pylori

may produce false negatives when performed within
four weeks of eradication therapy, other antibiotic
therapy, or treatment with bismuth or proton pump
inhibitors (PPIs).
Serological tests, while simple, are prone to be
very variable, and require validation in the particular
population being studied. Reports of false positive
antibody rates of around 30% in elderly people should
prompt caution in their use.7 Because it can take
months for antibody levels to fall, this method is
unsuitable for assessing eradication.
NSAIDs and H. pylori
The information available about whether these two
factors interact in causing ulcers is limited.The presence of H. pylori in patients with NSAID-associated
ulcers is (paradoxically) associated with a higher
healing rate with drugs which do not eradicate the
organism.3 Attempts to reduce ulcer incidence
amongst NSAID users by eradicating H. pylori prior
to anti-inflammatory use have not had consistent
results.3,8,9 A recent consensus conference viewed
NSAIDs and H. pylori as independent, though possibly additive, risk factors for the development of
ulcer disease.10
CLINICAL PRESENTATION AND
COMPLICATIONS
The overall incidence of peptic ulceration, and the
proportion of ulcers which are gastric, both increase
with increasing age.1,11 While older persons may describe epigastric pain related to meals, relieved by
eating or antacids, they often have an atypical history for ulcer disease: absent or trivial pain, weight
loss, anaemia.11 Bleeding is the most common complication; perforation is less common, with diagnosis often delayed by a paucity of abdominal signs;
obstruction is rare.
It is interesting to note that:
70% of persons hospitalised for ulcer complications are aged over 60;
80% of ulcer deaths occur in persons over 65 years,

with 74% of these deaths from gastric ulcers;

mortality is high in the elderly approximately
30% for complicated ulcers.1

MANAGEMENT PRINCIPLES
Uncomplicated Ulcers
Endoscopy is the preferred means of diagnosis, and
it permits the taking of biopsies, both to exclude
malignancy and for urease testing. Endoscopy is well
tolerated in older persons, and its use is preferable
to empirical therapy.
Drug therapy is aimed at ulcer healing, both for
symptom control, and to reduce complications. Other
issues to be addressed are whether to cease NSAIDs,
possibly substituting other analgesics, and when to
use co-therapy (to prevent NSAID-associated damage) or maintenance ulcer healing therapy (these issues are discussed in more detail below.)
Repeat endoscopy (possibly with biopsies) is
indicated to demonstrate ulcer healing of gastric ulcers, and to check for H. pylori eradication (when
appropriate). Verification of healing is not usually
advised for uncomplicated duodenal ulcers.
Complicated Ulcers
Admission to hospital is essential, for resuscitation
and investigation. Endoscopy provides an accurate
diagnosis, identifies those still bleeding or with a
higher probability of re-bleeding, and permits endoscopic therapy. Most bleeding ulcers stop spontaneously.12 Endoscopic therapy is effective in four out
of five actively bleeding ulcers, reducing the need for
urgent surgery.11,12 Surgery remains important for
dealing with continuing or recurrent bleeding resistant to endoscopic therapy, and is the preferred
treatment for perforation.
There is some evidence that high dose acid suppression may be effective in reducing re-bleeding,
and the need for surgery, in patients who have presented with bleeding ulcers.13,14 The precise role for
such therapy, in relation to endoscopic therapy, remains to be determined by appropriate trials.12 Until then, this area remains controversial.

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Table 2. Drugs used for ulcer healing

Duration

Efficacy

Comments

H2-antagonists
(full dose at night, or
half twice daily)
cimetidine 800 mg
famotidine 40 mg
nizatidine 300 mg
ranitidine 300 mg

6-12 weeks

Good healing;
high relapse rate if drug
ceased, or if H. pylori not
eradicated

Few interactions or adverse events

(although more common in those
aged over 70); gastric ulcers often
slower to heal; maintenance therapy
is an option

Proton pump inhibitors

(daily dose)
lansoprazole 30 mg
omeprazole 20 mg
pantoprazole 40 mg

4-8 weeks

More effective and

more rapid healing
than H2-antagonists

Particularly useful for NSAID ulcers

and for treatment failures with other
drugs

Prostaglandin agonist
misoprostol 800 g
(in 2-4 doses)

4-8 weeks

Similar efficacy to
H2-antagonists

Useful for NSAID ulcers (superior

to standard dose H2-antagonists for
NSAID gastric ulcers)

Cytoprotectants
colloidal bismuth subcitrate 108
mg four times daily (or 216 mg
twice a day)
sucralfate 1 g four times a day

4-8 weeks

Similar efficacy to
H2-antagonists

DRUGTHERAPY
NSAID Ulcers
Prevention of ulcers in NSAID users would be the
most logical approach to the problem in older persons. Misoprostol has been shown to be effective
therapy for prophylaxis of NSAID ulcers. Its major
limitation is associated abdominal cramping and/or
diarrhoea. A combination of misoprostol and
diclofenac (Arthrotec available in Australia through
the Repatriation, but not the general, Pharmaceutical Benefits Scheme) has been shown in several studies to produce fewer gastroduodenal ulcers than
diclofenac, piroxicam or naproxen alone.15 High dose
famotidine (40 mg twice daily) reduces the occurrence of NSAID-associated gastric ulcer, when compared with standard dose (20 mg twice daily) or placebo; either dose is effective prophylaxis for duodenal ulcer in NSAID recipients.16
When ulcers occur, the simplest approach is to:
stop the NSAID, substituting simple analgesics
and other non-drug means of management;
heal the ulcer with an appropriate drug (Table 2).
If the NSAID cannot be stopped, healing is slower.
Both H2-antagonists and proton pump inhibitors
have a very low incidence of side effects. Interactions with warfarin, benzodiazepines, and b-blockers
can be an issue when using cimetidine. Whether reported adverse effects, such as confusion in older
patients taking cimetidine, are due to the drugs, or
due to coexistent illness is not resolved.17
Two recent, double-blind, randomised trials compared omeprazole with misoprostol and ranitidine

Mostly used in triple therapy

regimens; maintenance therapy not
recommended
Not widely used

for healing NSAID ulcers and erosions when the

NSAID was continued (Table 3).2,3 In the first study,
for gastric ulcers, standard (but not high) dose
omeprazole was significantly better than misoprostol
200 mg four times daily. For duodenal ulcers, both
doses of omeprazole were significantly better.2 In the
second study, both omeprazole doses were significantly better than ranitidine 150 mg twice daily for
healing gastric ulcers; omeprazole 20 mg was significantly better than ranitidine for duodenal ulcers.3
Table 3. Healing rates at 8 weeks of NSAID ulcers
(while NSAID is continued)2,3
Ulcer type
Gastric
Duodenal

Omeprazole Omeprazole
20 mg
40 mg
87%
93%

80%
89%

Omeprazole Omeprazole
20 mg
40 mg
Gastric
Duodenal

84%
92%

87%
88%

Misoprostol
800 g
73%
77%
Ranitidine
300 mg
64%
81%

Omeprazole was the superior drug in both trials. However, the healing rates for misoprostol in
duodenal and gastric ulcer, and ranitidine in duodenal ulcer were not that different; it is possible that
such differences at eight weeks simply represented
more rapid healing with the more potent acid inhibitor, omeprazole.
Once NSAID-associated ulcers have been healed,
co-therapy with omeprazole 20 mg daily has been

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shown to be an effective way of preventing ulcer

recurrence in those who need to continue to use
NSAIDs.2,3 Misoprostol, 200 mg twice daily, was
about as effective as omeprazole in preventing gastric ulcers, but less so for duodenal (Table 4). Side
effects leading to cessation of therapy were more
common with misoprostol.2 Ranitidine, 150 mg twice
daily, was less effective than omeprazole as co-therapy;
this difference was more marked for gastric than for
duodenal ulcers.3 Other proton pump inhibitors may
prove in the future to have a similar effect to
omeprazole.
Table 4. Ulcer relapses at 6 months during co-therapy
(while NSAID is continued)2,3
Ulcer type
Gastric
Duodenal

Gastric
Duodenal

Omeprazole
20 mg

Misoprostol
400 g

Placebo

13%
3%

10%
10%

32%
12%

Omeprazole
20 mg

Ranitidine
300 mg

5.2%
0.5%

16.3%
4.2%

Co-therapy with misoprostol in NSAID users

has been shown to prevent ulcer complications; the
same cannot yet be said for co-therapy with
omeprazole. However, its greater efficacy is likely
to translate into reduced complication rates, for ulcer complications cannot occur if ulcers are not
present.2,3
H. pylori related ulcers
Successful eradication of the organism should lead
to ulcer healing, and a low incidence of gastric or
duodenal ulcer recurrence. Eradication is indicated
for H. pylori positive individuals with duodenal
or gastric ulcer, current or previously documented.
H. pylori eradication reduces complications from peptic ulcer disease.
Combinations of three drugs (triple therapy)
have been shown to be necessary to eradicate this
organism. Most combinations consist of either bismuth subcitrate, ranitidine bismuth subcitrate (RBC,
not available in Australia), or a PPI, plus two antibiotics out of amoxycillin, metronidazole, clarithromycin, or tetracycline. Clarithromycin is only
available through the Pharmaceutical Benefits
Scheme as part of a single-script combination (Losec
Hp7 or Klacid Hp7). Many commonly used regimens are reported to achieve eradication rates around
80 to 90%. However, the rates actually achieved may
be as low as 50 to 70% when metronidazole resist-

ant strains of H. pylori are present.18,19 Metronidazole resistance rates in Australia vary greatly, but
may be greater than 30%. The trend overseas has
been for metronidazole resistance rates to increase
over time.With resistant strains, the eradication rates
achieved by PPI-based therapies fall by 5-10%; with
bismuth-based regimens the eradication rate may
drop to around 50%. Combinations which include
clarithromycin are generally more effective (over
90%). Currently there is little evidence of
clarithromycin resistance in this country; it remains
to be seen whether it will increase.
Compliance is the other important factor in
achieving successful eradication.19 Side effects from
medication seem to be most common with metronidazole (nausea, a disulfiram-like reaction with alcohol) and bismuth (nausea, diarrhoea, blackened
tongue and stools). Clarithromycin may cause disturbed taste, and all the antibiotics may lead to candidiasis or, rarely, to pseudomembranous colitis.
Currently recommended therapies for use in the
Asia Pacific region are listed in Tables 5.10,19 Several
single-pack combinations are available in Australia
through the Pharmaceutical Benefits Scheme (Table 6). Small differences between the regimens relate to issues of drug availability, or to a two-week
course of therapy being marketed in Australia, when
many authors would recommend using the drugs for
one week. These differences probably do not alter
efficacy, but longer duration of therapy may worsen
compliance or increase side effects.
The management of treatment failure is more
complex, and there is insufficient evidence to make
firm recommendations. One approach, when metronidazole has been used in the first regimen, is to
repeat the triple therapy, replacing metronidazole
with amoxycillin. Some authors advocate giving a
second course of PPI-amoxycillin-clarithromycin. Alternatively, a one-week course of bismuth-metronidazole-tetracycline, with added proton pump inhibitor, has been proposed.10
With increasing use of eradication therapy, we
can expect to see fewer people requiring maintenance acid suppression for ulcer disease. Nevertheless, there remain some patients, often elderly, for
whom maintenance therapy, with an H2-antagonist
or an acid pump inhibitor, is reasonable where
eradication therapy has failed, or is contraindicated
because of drug side effects or likely interactions.
NSAIDs and H. pylori
In the absence of appropriate trials, it seems prudent
to eradicate H. pylori in those NSAID ulcer patients
who also have the organism.Whether H. pylori eradi-

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Table 5. Recommended therapies for Helicobacter pylori eradication10,19

Drug combination
Proton pump inhibitor,
metronidazole
OR amoxycillin,
clarithromycin
Ranitidine bismuth subcitrate,*
metronidazole
OR amoxycillin,
clarithromycin

Duration of treatment
(weeks)

Eradication
rate (%)

Standard dose (twice daily)

400 mg twice daily
1000 mg twice daily
500 mg twice daily

>90

400 mg twice daily

400 mg twice daily
1000 mg twice daily
500 mg twice daily

>90

Standard dose (twice daily)

400 mg twice daily
1000 mg twice daily

80-90

120 mg four times daily

400 mg twice daily
500 mg four times daily

80-90

Dose

If clarithromycin is not available, consider either of:

Proton pump inhibitor,
metronidazole,
amoxycillin
Colloidal bismuth subcitrate,
metronidazole,
tetracycline

*not currently available in Australia; colloidal bismuth subcitrate available in 108 mg strength in Australia
Table 6. Single-script Helicobacter pylori eradication therapies available through the Australian Pharmaceutical
Benefits Scheme
Product
Losec Helicopak (Astra)
omeprazole
metronidazole
amoxycillin
Helidac (Pharmacia Upjohn)
bismuth
metronidazole
tetracycline
Losec Hp7 (Astra)
Klacid Hp7 (Abbott)
omeprazole
amoxycillin
clarithromycin

Dose
20 mg twice daily
400 mg three times daily
500 mg three times daily
108 mg four times daily
200 mg three times daily, 400 mg at night
500 mg four times daily

Duration of treatment
(weeks)

Eradication
rate (%)

90

80-95

>90

20 mg twice daily
500 mg twice daily
500 mg twice daily

cation should be attempted before NSAID use, to

reduce the probability of ulcers arising, is controversial.The Asia Pacific Consensus group advocated
eradication therapy in persons with an ulcer history
who required NSAID therapy, but did not recommend routine testing for H. pylori prior to initiating
treatment with NSAIDs.10
FUTURE DIRECTIONS
The problem of drug resistance may change our
approach to H. pylori. A program monitoring antibiotic sensitivity patterns around Australia is now starting.18 The discovery, in animals, that immunisation
could cure existing infection promises to move the
focus away from drugs in eradication and prevention of H. pylori infection.20 Knowledge of the complete genome of H. pylori should aid the future development of genetically engineered therapeutic

vaccines using multiple bacterial antigens.21

NSAID ulcers may be more easily prevented, if
future research can predict which persons are at greatest risk, and enable targeted prophylaxis. Present
NSAIDs inhibit the enzyme cyclo-oxygenase (COX).
Different forms of this enzyme occur in different tissues: inhibition of the COX-1 form in gastric mucosa seems to explain how these drugs cause upper
gastrointestinal toxicity; inhibition of COX-2 in inflamed joints leads to the intended effect of the drugs.
NSAIDs in current use are not specific for the COX2 enzyme. If more selective anti-inflammatory drugs
with minimal or no COX-1 inhibition can be developed, gastroduodenal toxicity might be prevented.
CONCLUSION
Peptic ulcer disease has a disproportionate impact
on the health of older persons in our community.

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Guidelines adopted recently in the US, Europe and

Asia for management of H. pylori all recommend
eradication of the organism whenever it is present in
ulcer disease, regardless of NSAID involvement.
Effective means are available for the treatment of
NSAID ulcers when the drug cannot be stopped,
and for prevention of ulcer recurrence thereafter.2,3
These approaches offer the prospect of preventing
ulcer complications.
Neither H. pylori eradication regimens, nor therapies to treat or prevent NSAID ulcer recurrence, are
perfect at present, but they have substantially advanced the management of peptic ulcers. Both should
improve the wellbeing of older persons with ulcers,
and contribute to improved morbidity and mortality.
References
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A, Swannell AJ, et al. Omeprazole compared with misoprostol
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3. Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, van
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