386 the red section
Treatment of GERD and Proton Pump Inhibitor
Use in the Elderly: Practical Approaches and
Frequently Asked Questions
Shannon Scholl, MD, MPH1, Evan S. Dellon, MD, MPH1 and Nicholas J. Shaheen, MD, MPH1
Am J Gastroenterol 2011;106:386–392; doi:10.1038/ajg.2010.409
The care of acid-related diseases such as
gastroesophageal reflux disease (GERD) in
the elderly patient presents challenges not
found in younger populations. Concurrent
comorbidities, medication interactions,
and the physiology of aging all conspire
to change the presentation and natural
history of these diseases in older patients.
Clinicians caring for geriatric patients
must therefore be aware of these changes
to provide optimal care for GERD and to
use acid-suppressive therapies to their best
advantage in the elderly population.
Below, we address several questions
that commonly occur in caring for acid-
related disease in the elderly population.
Although the recommendations proposed
below do not represent the only, or neces-
sarily the “best,” way to care for all elderly
patients, they are solutions supported
by evidence found in elderly cohorts to
produce satisfactory results. The United
Nations’ definition of “elderly” is those
aged 60 or older, but, given the average
life expectancy in the United States, the
discussion below is focused primarily on
those 70 years and older.
Does the clinical presentation of GERD
change as patients age?
In the elderly population, as in the general
population, more than 40% have occasional
symptoms of GERD and 20% have weekly
1
Center for Esophageal Diseases and Swallowing,
University of North Carolina at Chapel Hill, Chapel
Hill, North Carolina, USA. Correspondence:
Nicholas J. Shaheen, MD, MPH, Center for
Esophageal Diseases and Swallowing, University
of North Carolina School of Medicine, CB#7080,
Chapel Hill, North Carolina 27599-7080, USA.
E-mail: nshaheen@med.unc.edu
The American Journal of Gastroenterology
symptomatic GERD. But as patients age,
the severity of heartburn diminishes, while
its complications become more frequent
(1–3). In a study of 12,000 patients aged
18–75 with endoscopically documented
erosive esophagitis, severe heartburn was
seen in 30% of patients aged more than
70 years with erosive esophagitis (com-
pared with 47% of patients aged 31–40),
and severe esophagitis (defined as Los
Angeles grade C or D) was seen in 35% of
elderly patients vs. 25% of patients aged
31–40 among those with severe heartburn
(Figures 1 and 2) (4). Thus, while elderly
patients may have severe heartburn, severe
esophagitis may be present without the
hallmark accompanying symptoms. This is
probably due to several factors, including
decreased perception of mucosal damage.
Elderly patients without the typical symp-
tom of heartburn may instead complain of
more atypical symptoms, including respi-
ratory symptoms and vomiting (5). This
has important implications for patient
management. Aware clinicians should
have a low threshold for investigation and/
or empirical therapy in this patient popu-
lation. Upper endoscopy in the elderly
with GERD will demonstrate a higher
yield of Los Angeles grade C or D erosive
esophagitis, Barrett’s esophagitis, and ade-
nocarcinoma and, in most subjects, can be
done with a great degree of safety (6,7).
What are the most common side effects
of proton pump inhibitors?
Most mortality in GERD results from
esophageal adenocarcinoma. All data
suggesting that proton pump inhibitors
(PPIs) retard the development of dysplasia
nature publishing group
and/or cancer are retrospective and weak
(8–10). Therefore, for most subjects suf-
fering from GERD, the medication is used
primarily to address symptoms. Although
the decrement in quality of life associated
with GERD is substantial (11,12), the low
rate of morbidity and mortality means
that medications used to address GERD
must have excellent safety profiles to jus-
tify their use. Diarrhea, abdominal pain,
constipation, and headache are the most
common side effects of PPIs but are limit-
ing in relatively few patients and typically
respond to dose reduction or discontinu-
ation in those subjects. The risk of fundic
gland polyps (lesions with negligible, if
any, risk of dysplasia) may be increased
(13). No data support the cessation of PPI
use in subjects in whom they are other-
wise indicated on account of the develop-
ment of fundic gland polyps.
Serious complications of PPI use
appear to be rare and may result from
profound acid suppression and secondary
hypergastrinemia, hypochlorhydria, and
achlorhydria. The incidence of antibiotic-
associated Clostridium difficile colitis is
twice as high in PPI users. The putative
mechanism of this increased risk is that
hypochlorhydria prevents sterilization
of the upper gastrointestinal (GI) tract,
permitting colonization by pathogenic
species (14). By the same mechanism, the
risk of community-acquired pneumonia
is increased approximately twofold (15).
The same effect is seen, to a lesser degree,
in users of H2-receptor antagonists,
which supports the theory that reduc-
tion of the gastric acid barrier may be to
blame. However, studies investigating the
Volume 106 | march 2011 www.amjgastro.com

40
35 Patients (%)
30
25
20
15
10
0 0
<21 21−30 31−40 41−50
Figure 1.  Prevalence of severe esophagitis by age-decade cohort.
(Adapted from ref. 4.)
effect of PPIs on community-acquired
pneumonia have been confounded by the
diagnosis of GERD, and it is unknown
whether GERD itself or the PPI use is the
predisposing factor. Concerns regard-
ing hip fracture in the setting of PPI use
are addressed below. Additionally, recent
data suggest the potential for significant
medication interactions, which have
raised concerns about increased cardiac
events in subjects on PPIs. These issues
are also discussed below.
Given that both community-acquired
pneumonia and C. difficile infection are
more common and carry higher risks of
morbidity and mortality as patients age
(16), the associations described above
deserve special attention in the elderly
population. However, it should be noted
that the majority of data supporting these
more significant risks of PPI therapy are
derived from retrospective studies of large
databases, and such research is subject to
multiple forms of bias. Despite the weak-
ness of the data supporting these risks,
to minimize side effects, PPIs should be
applied only when clinically indicated, at
the minimum effective dose.
Is it appropriate to change the PPI dose
for elderly or obese patients?
There are no data to support the use
of reduced doses of PPIs on the basis
of age alone. Pharmacokinetic studies
of omeprazole and lansoprazole show
© 2011 by the American College of Gastroenterology
50
40
30
20
10
51−60 61−70 >70 <21 21−30
Figure 2.  Prevalence of severe heartburn by age-decade cohort.
(Adapted from ref. 4.)
reduced clearance (17,18) and increased
bioavailability (17) of these PPIs in
patients in the eighth and ninth decades
of life as compared with younger patients,
but, because of considerable overlap in the
pharmacokinetic profiles of the groups,
dose adjustment is not recommended.
There is no difference in the metabolism
of esomeprazole in elderly and middle-
aged patients with GERD (19).
PPI metabolism occurs via the cyto-
chrome P450 system in the liver (20).
Clinically significant abnormalities of PPI
metabolism are rare and do not increase
in a healthy aged population. In elderly
subjects with normal hepatic function,
dose adjustment is not recommended.
Obesity is an independent risk factor for
GERD and erosive esophagitis, so these
patients frequently require PPI therapy.
There are many reasons to suspect that
an altered dose of PPI might be required
for obese patientsthey may have more
severe symptoms or a larger volume of
distribution of drug, and they often have
comorbid liver disease in the form of
hepatic steatosis. However, to date, no
study has shown an altered pharmacoki-
netic profile in obese patients for either
PPIs or H2-receptor antagonists. In fact,
despite the increased severity of GERD
with increasing body mass index (21,22),
there is no difference in the response to
comparable PPI doses in obese compared
with lean patients.
the red section 387
Patients (%)
31−40 41−50 51−60 61−70 >70
Is there a significant interaction
between PPIs and clopidogrel?
Concerns about PPI use in the setting
of concurrent clopidogrel therapy were
heightened in 2009, when a study by Ho
et al. in JAMA showed a higher rate of
acute coronary syndrome and/or mortal-
ity in 8,205 veterans who used PPIs and
clopidogrel (29.8%) vs. clopidogrel alone
(20.8%) (23). This was a retrospective
cohort study and had several limitations
inherent to that design. However, there
is a plausible biological mechanism sup-
porting the interaction: ex vivo platelet
aggregation studies showed an interaction
between PPIs and clopidogrel due to inhi-
bition of the CYP enzyme subclass that
converts clopidogrel to its active metabo-
lite (24). Subsequent platelet aggregation
assays supported an interaction but did
not evaluate the clinical results of such an
interaction. Later in 2009, an analysis of
2,208 subjects enrolled in a French reg-
istry following acute coronary syndrome
failed to show a difference between clopi-
dogrel users taking PPIs and those taking
clopidogrel alone (25).
Two recent clinical studies and one in
vitro aggregometry study evaluated the
effect of pantoprazole, a weaker inhibi-
tor of the CYP2C19 enzyme, on the effect
of clopidogrel. All of them showed less
interaction with pantoprazole than with
omeprazole (26,27) or esomeprazole (27)
or in comparison with all other PPIs (28),
The American Journal of Gastroenterology
388 the red section
raising hopes that pantoprazole could
be safely used in these patients. How-
ever, a more recent retrospective study of
1,033 patients readmitted to the hospital
for acute myocardial infarction or stent
placement showed similar rates of rehos-
pitalization for users of pantoprazole vs.
other PPIs (29).
Results of an industry-sponsored study
evaluating the clinical significance of an
interaction between PPIs and clopidogrel
have recently been released in abstract
form. The COGENT (Clopidogrel and the
Optimization of Gastrointestinal Events)
study randomized subjects in need of
clopidogrel because of either recent acute
coronary syndrome or stent placement
into a clopidogrel and an omeprazole
plus clopidogrel group. All patients were
maintained on dual antiplatelet therapy
with aspirin. Deaths from cardiovascular
events were then assessed in both groups
over a median of 4 months. The resulting
survival curves for myocardial infarc-
tion, revascularization, and composite
cardiovascular events for the treatment
and placebo groups are superimposable,
providing striking evidence for a lack
of interaction between omeprazole and
clopidogrel. However, the survival curves
for composite GI events do show a pro-
tective effect of omeprazole (P = 0.007),
suggesting that PPI use can ameliorate the
GI effects of aspirin in this patient popula-
tion. These results from a large, random-
ized, well-controlled prospective trial
provide evidence that omeprazole is safe
when used with dual antiplatelet therapy
and provides important protection from
GI complications. However, the validity
of the trial was challenged because of its
premature terminationthe sponsor of
the trial declared bankruptcy, and all trial
proceedings immediately halted before
completion of the study (30).
Because of the unclear nature of the data
surrounding an interaction between PPIs
and clopidogrel, on 17 November 2009, the
US Food and Drug Administration (FDA)
issued a warning regarding the concomi-
tant use of clopidogrel and PPIs, stating,
“New data show that when clopidogrel and
omeprazole are taken together, the effec-
tiveness of clopidogrel is reduced. Patients
The American Journal of Gastroenterology
Table 1.  Risk categories for endoscopic procedures
High risk
Polypectomy
Biliary sphincterotomy
Pneumatic or bougie dilation
PEG placement
EUS with FNA
Laser ablation and coagulation
Treatment of varices
EGD, esophagogastroduodenoscopy; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endo-
scopic ultrasound; FNA, fine-needle aspiration; PEG, percutaneous endoscopic gastrostomy.
Adapted from ref. 43.
at risk for heart attacks or strokes who use
clopidogrel to prevent blood clots will not
get the full effect of this medicine if they
are also taking omeprazole” (31). Given
the divided nature of the data on this issue,
the need for the warning is unclear. An
alternative approach being used by some
physicians—dosing one medication in the
morning and the other at night—may be
ineffective. The most recent package insert
for clopidogrel reports an unreferenced
study of 72 patients that showed that split
dosing did not reduce the interaction. For
now, physicians should warn patients of
a potential interaction. When possible,
avoidance of coadministration of omepra-
zole and clopidogrel may be warranted
until the potential interaction is better
understood. In cases of patients who are
considered to be at high risk for GI bleed-
ing, the risk of reduced activity of clopi-
dogrel must be weighed against the risk of
GI bleeding, and decisions about treatment
must be made on a case-by-case basis.
What other medication interactions do
I need to consider when prescribing
PPIs?
Polypharmacy is common in elderly
populations, and therefore medication
interactions take on special importance
in older patient populations. Fortunately,
there have been very few significant med-
ication interactions associated with PPI
use. As noted above, metabolism by the
CYP450 superfamily of enzymes may lead
to rare inhibition or potentiation of simi-
Low risk
Diagnostic: EGD ± biopsy
Diagnostic: flexible sigmoidoscopy ± biopsy
Diagnostic: colonoscopy ± biopsy
ERCP without sphincterotomy
Biliary/pancreatic stent without sphincterotomy
EUS without FNA
Enteroscopy
larly metabolized drugs, such as warfarin,
diazepam, and phenytoin, but these occur
so rarely (less than one adverse event per
million prescriptions) that they are not
considered clinically significant (32–34).
PPIs are metabolized via the CYP2C19
subclass, a minor pathway for metabolism
of the weaker R-warfarin enantiomer of
warfarin, raising the levels of this minor
metabolite by up to 12% (35). Omeprazole
may be the most active in this regard (36).
Although not formally recommended, in
subjects who have had marked lability of
drug levels or in those with severe clini-
cal syndromes, the clinician may wish
to check for stability of the international
normalized ratio or phenytoin level after
a new PPI prescription is initiated.
Should PPIs be used to protect against
GI complications of low-dose aspirin?
Given the high prevalence of coronary
artery disease in the elderly, the use of
cardioprotective aspirin is frequent in
this population (37). Since the risk of
gastroduodenal ulceration also increases
with age, prophylaxis against the GI
complications of aspirin in the setting
of cardioprotection is a commonly faced
clinical issue in the elderly population.
Aspirin exerts its gastropathic effects by
direct epithelial damage and by inhibi-
tion of mucosal prostaglandin produc-
tion, which reduces mucosal defenses
including mucus and bicarbonate secre-
tion, reducing blood flow, and reducing
epithelial-cell turnover and repair (38).
Volume 106 | march 2011 www.amjgastro.com
 the red section 389

other NSAIDs do not increase the risk of

Table 2.  Summary of recommendations for anticoagulation cessation
significant bleeding with polypectomy and
Avoid cessation of antiplatelet therapies after PCI with stent placement when possible sphincterotomy (43,53–55), aspirin should
Avoid cessation of clopidogrel (even when aspirin is continued) within the first 30 days after PCI and be discontinued for colonoscopy or endo-
either DES or BMS when possible scopic retrograde cholangiopancreatog-
Defer elective endoscopic procedures—possibly for up to 12 months, if clinically acceptable, from the
raphy only if there is an additional strong
time of PCI and DES placement clinical indication to do so. Cessation of
clopidogrel alone beyond 30 days from
Perform high-risk endoscopic procedures 5–7 days after clopidogrel therapy and 3–5 days after
cilostazol cessation. Aspirin should be continued when possible bare-metal stent placement is common and
does not confer increased risk of thrombo-
Resume antiplatelet therapy after the procedure, once hemostasis has been achieved
sis over a short period of time. Similarly,
Continue clopidogrel and aspirin in patients undergoing elective low-risk endoscopic procedures short-term cessation of clopidogrel alone
BMS, bare-metal stent; DES, drug-eluting stent; PCI, percutaneous coronary intervention. beyond 6 months from drug-eluting stent
Adapted from ref. 45. placement does not confer significant
risk if aspirin is continued (46). But as a
general principle, for elective procedures
The risk of GI bleeding in patients using atography (without sphincterotomy), and that would require interruption of anti-
low-dose aspirin is approximately twice colonoscopy (without polypectomy) do not platelet therapy (such as routine screening
the rate with placebo and carries a 5% require cessation of anticoagulants. Biopsy colonoscopy with polypectomy), deferral
case-fatality rate when severe enough with forceps is considered a low-risk proce- until 12 months after percutaneous coro-
to require admission (39). The risk of dure. High-risk procedures (polypectomy, nary intervention with drug-eluting stent
bleeding is increased in those who have percutaneous endoscopic gastrostomy placement is preferable.
a history of prior GI events, are older, placement, fine-needle aspiration, sphinc- There is no evidence that bridging with
or use anticoagulants, corticosteroids, terotomy, and dilatation) do warrant cessa- heparin reduces the risk of thrombotic
or high-dose or multiple nonsteroidal tion of anticoagulation, which is typically events when antiplatelet therapy is dis-
anti-inflammatory drugs (NSAIDs). discontinued 3–5 days (cilostazol) or 5–7 continued (56,57). Table 2 summarizes
Cyclooxygenase-2-selective NSAIDs are days (aspirin, clopidogrel) before the pro- the recommendations for anticoagulation
less gastropathic, but use of low-dose cedure (Table 1) (43). cessation.
aspirin largely obviates their gastropro- Clopidogrel–aspirin dual therapy is
tective effects. PPIs have been found to used to prevent stent thrombosis following When is it appropriate to do screening
be superior to full-dose ranitidine and percutaneous coronary intervention, as upper endoscopy on the elderly patient
placebo for the healing of NSAID-asso- primary prevention of myocardial infarc- with chronic GERD?
ciated ulcers irrespective of Helicobacter tion in patients with unstable angina or Weekly heartburn symptoms are present
pylori status, in a dose-dependent man- nonintervenable coronary artery disease, in 20% of elderly patients and, as noted
ner (40–42). The lowest effective dose of and as secondary prevention of myocar- above, often portend more severe endo-
aspirin (and other NSAIDs) should be dial infarction and cerebrovascular acci- scopic disease than comparable symptoms
used, and risk factors for bleeding should dents and in those with a prior history of in younger patients. Increasing age is a risk
be assessed, with application of PPIs in the same (44,45). If clopidogrel alone must factor for Barrett’s esophagus and esopha-
high-risk groups, as noted above. be stopped within the first 30 days follow- geal adenocarcinoma. But the presence of
ing bare-metal stent or drug-eluting stent heartburn is not a reliable predictor for the
How should we manage patients placement, the risk of restenosis is low, presence of Barrett’s esophagus in this age
receiving antiplatelet therapy who need estimated at 1–4%, the highest risk being in group, because conversion to columnar
endoscopy? patients with longer stent lengths (suggest- epithelium may be associated with loss of
In considering an endoscopic procedure on ing more severe disease) and lower ejection symptomatic heartburn (58). Even when
an anticoagulated patient, the risk of ongo- fraction (46–51). Cessation of both aspirin present, symptomatic heartburn is not
ing or procedure-related bleeding must be and clopidogrel is associated with a higher a reliable risk factor for Barrett-related
weighed against the risk of thromboembo- risk of acute coronary syndrome and ST- cancer because 40% of those with a new
lic events such as cerebrovascular accident elevation myocardial infarction and also diagnosis of esophageal adenocarcinoma
or myocardial infarction following dis- confers a shorter time to stent thrombosis report an absence of prior weekly heart-
continuation of anticoagulation. Low-risk (7 days for those on no antiplatelet therapy burn. Clearly, any elderly patient with
procedures such as diagnostic esophago- vs. 122 days for patients still on aspirin) heartburn that is unresponsive to PPI and/
gastroduodenoscopy, endoscopic ultra- (52). As the current American Society for or with dysphagia should be considered for
sound (without fine-needle aspiration), Gastrointestinal Endoscopy guidelines endoscopy. But screening of patients with
endoscopic retrograde cholangiopancre- indicate that standard doses of aspirin and uncomplicated chronic heartburn of any

© 2011 by the American College of Gastroenterology The American Journal of Gastroenterology

390 the red section
age is controversial, because of the lack of
direct evidence demonstrating a mortality
benefit. As a result, the value of endoscopic
screening of subjects with chronic GERD
symptoms of any age for Barrett’s esopha-
gus is highly contested. Economic model-
ing suggests that screening of white men
aged more than 50 years with heartburn
symptoms for at least 5 years is probably
cost-effective (59). Moreover, regardless
of age, any patient with alarm symptoms
such as weight loss, anemia, dysphagia,
or GI bleeding should undergo screening
endoscopy.
When is it appropriate to stop
performing surveillance endoscopy
for elderly patients with Barrett’s
esophagus?
When Barrett’s esophagus is diagnosed,
surveillance for dysplasia and adenocarci-
noma is often performed. Approximately
5% of patients diagnosed with Barrett’s
will develop adenocarcinoma, and the risk
is greatest in patients aged 65–74 years
(60–62). However, the risk of cancer in any
given patient in a calendar year is small,
estimated at 0.5% per year. For this reason,
frequent surveillance of all patients with
nondysplastic Barrett’s is not cost-effec-
tive (59). Current guidelines recommend
repeating endoscopy with four-quadrant
biopsies within one year after the initial
diagnosis of Barrett’s to detect any preva-
lent dysplasia. Following that, decision-
analysis studies suggest that endoscopic
surveillance of persistent nondysplastic
Barrett’s could be performed every 5 years
(63). Surveillance should be ended when
the life expectancy is less than 1 year or the
patient could not be expected to tolerate
endoscopic or surgical therapy in the event
of a cancer diagnosis (64). Given the rise
of endoscopic therapy for dysplastic Bar-
rett’s esophagus (65,66), and the increasing
life expectancy of the elderly in the United
States, thinking about when to stop surveil-
lance is evolving. Given that most patients
who can tolerate surveillance endoscopy
can also tolerate some form of endoscopic
therapy, and that the onset of adenocarci-
noma of the esophagus is late in life, cli-
nicians should not use chronological age
alone as a reason to stop surveillance. Can-
The American Journal of Gastroenterology
cer death may be averted and life extended
in otherwise healthy subjects without life-
limiting comorbidity even late in life with
well-timed endoscopic intervention.
Does PPI use affect vitamin B12
absorption?
Vitamin B12 is liberated from protein
sources with the help of gastric acid. There
has been concern that PPI use would inter-
fere with this process, leading to B12 malab-
sorption and deficiency. Studies comparing
healthy controls with PPI users have had
conflicting results (67–69). There may be
a decline in B12 levels in long-term (>3-
year) users of PPI, but this has not been
shown to result in clinical disease (70).
The elderly are at risk for development of
pernicious anemia and should be screened
for B12 deficiency if macroblastic anemia is
detected. Otherwise, routine monitoring
of vitamin B12 or other vitamins in chronic
PPI users is not necessary.
Does PPI use increase the risk of hip
fracture in the elderly?
A 2006 article by Yang et al. (71) in JAMA
gained media attention by suggesting that
PPI use conferred an increased risk of hip
fracture in patients 50 years of age or older.
In this study, higher dose and duration of
PPI use conferred an odds ratio (OR) of
1.59 (95% confidence interval 1.39–1.80)
for use for more than 3 years. Two other
studies found similar results, with the larg-
est odds ratio being 1.92 (1.16–3.18) after
7 years of PPI use (72,73). All of the studies
were retrospective case-control designs (a
design that is subject to multiple forms of
bias), and none of the studies controlled for
vitamin D levels or fall risk. Importantly, a
recent study was unable to show an asso-
ciation of PPIs with increased fracture in
those without risk factors (74).
Reduced calcium absorption in the
hypochlorhydric stomach is a proposed
mechanism of increased fracture risk.
This concern originates from studies of
human subjects whose plasma calcium
and 24-hour urinary calcium levels were
reduced following concomitant calcium
carbonate and PPI administration (75).
A recent case–control study evaluated the
effect of PPIs on osteoporosis and bone
mineral density in a Manitoba registry of
21,933 patients (76). These investigators
found no relationship between PPI use and
osteoporosis or PPI use and loss of bone
mineral density over 5 years. These data
cast doubt on the hypothesis that PPIs pro-
mote bone loss. Regardless of the divided
nature of these data, on 25 May 2010, the
FDA issued a warning regarding the pos-
sible link between hip, wrist, and spine
fractures and PPI use. The FDA mandated
changes in the labels of all prescription
and over-the-counter PPI preparations
on the basis of these data and advised that
“healthcare professionals and users of pro-
ton pump inhibitors should be aware of the
possible increased risk of fractures of the
hip, wrist, and spine with the use of pro-
ton pump inhibitors, and weigh the known
benefits against the potential risks when
deciding to use them” (77).
In summary, studies evaluating PPIs
and fracture risk are methodologically
limited, and divided in their conclu-
sions. There is some suggestion of a small
increase in fracture risk with an odds
ratio less than 2. The mechanism of any
increase in fracture risk is unclear but may
not occur through reduction of bone den-
sity. PPIs should be used only for appro-
priate clinical indications at the lowest
effective dose, and the possible increased
risk of hip fracture should be disclosed
to patients. In those who require high-
dose, long-term PPIs, osteoporosis and
fall risk should be assessed and modified
as appropriate through the use of calcium
supplements and/or bisphosphonates.
Conclusion
In summary, elderly patients represent
a special population with respect to PPI
therapy and acid-peptic disease. They have
more severe esophagitis and are at the
highest risk for complications of GERD,
including Barrett’s esophagus and esopha-
geal adenocarcinoma. They often have
comorbidities that require NSAIDs or
antiplatelet therapy, which put them at risk
for GI bleeding and represent challenges
for management during endoscopic inter-
vention. And they are often on multiple
medications, raising concern regarding
medication interactions.
Volume 106 | march 2011 www.amjgastro.com

Fortunately, PPI use has a favorable side-
effect profile and few significant drug inter-
actions. Adverse effects of PPI therapy may
include an increased risk of C. difficile coli-
tis, community-acquired pneumonia, and
hip fracture. The latter is an area of active
research and current controversy. A com-
mon-sense approach to pharmacotherapy
should be applied: prescribe PPIs only to
patients for whom therapy is indicated, and
do so at the smallest effective dose.
The effect of PPIs on clopidogrel is an
area of active research. A recent large pro-
spective study showed no effect of PPIs on
myocardial infarction, but the FDA has
placed a warning on clopidogrel, citing this
interaction. The package insert does not
support split dosing as a means of avoiding
the interaction. For now, physicians should
dose PPIs judiciously in these patients and
warn them of the potential interaction.
In the setting of recent coronary stent
placement, prior stent thrombosis, or
prior cerebrovascular accident, clopi-
dogrel should be discontinued only if
necessary, and preferably not within the
first 30 days following stent placement,
when the risk of in-stent stenosis is high-
est. In all situations, aspirin should be
continued as monotherapy if possible,
even in high-risk procedures. A PPI is
recommended as gastroprotection in
elderly patients who require daily aspirin
or other NSAID therapy.
Physicians should have a low threshold
for prescribing PPIs for elderly patients
who have symptomatic GERD and should
be alert for atypical presentations. There is
no evidence for adjusting the dose of PPI
for elderly or obese patients. Chronologi-
cal age should not be used as a sole crite-
rion for discontinuing Barrett’s dysplasia
surveillance; virtually any patient who can
tolerate endoscopy can tolerate endoscopic
ablative therapies.
CONFLICT OF INTEREST
Guarantor of the article: Nicholas J.
Shaheen, MD, MPH.
Specific author contributions:
Shannon Scholl and Evan S. Dellon
authored the paper; Nicholas J. Shaheen
edited the paper.
Financial support: None.
© 2011 by the American College of Gastroenterology
Potential competing interests:
Dr Shaheen receives research funding from
Takeda Pharmaceuticals, AstraZeneca,
Procter & Gamble, BÂRRX Medical, CSA
Medical, and Oncoscope Inc. He is a con-
sultant for AstraZeneca, CSA Medical, and
Oncoscope Inc.
References
1. Zhu H, Pace F, Sangaletti O et al. Features of
symptomatic gastroesophageal reflux in elderly
patients. Scand J Gastroenterol 1993;28:235–8.
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