The n e w e ng l a n d j o u r na l of m e dic i n e

clinical practice

Gastroesophageal Reflux Disease

Peter J. Kahrilas, M.D.

This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the authors clinical recommendations.

A 53-year-old man, who is otherwise healthy and has a 20-year history of occasional
heartburn, reports having had worsening heartburn for the past 12 months, with
daily symptoms that disturb his sleep. He reports having had no dysphagia, gastroin-
testinal bleeding, or weight loss and in fact has recently gained 20 lb (9 kg). What
would you advise regarding his evaluation and treatment?

The Cl inic a l Probl em

From the Division of Gastroenterology, Gastroesophageal reflux disease is the most common gastrointestinal diagnosis re-
Feinberg School of Medicine, Chicago. Ad- corded during visits to outpatient clinics.1 In the United States, it is estimated that
dress reprint requests to Dr. Kahrilas at the
Feinberg School of Medicine, 676 St. Clair 14 to 20% of adults are affected, although such percentages are at best approxima-
St., Suite 1400, Chicago, IL 60611-2951, tions, given that the disease has a nebulous definition and that such estimates are
or at [email protected]. based on the prevalence of self-reported chronic heartburn.2 A current definition of
N Engl J Med 2008;359:1700-7. the disorder is a condition which develops when the reflux of stomach contents causes
Copyright 2008 Massachusetts Medical Society. troublesome symptoms (i.e., at least two heartburn episodes per week) and/or
complications.3 Several extraesophageal manifestations of the disease are well rec-
ognized, including laryngitis and cough (Table 1). With respect to the esophagus,
the spectrum of injury includes esophagitis (Fig. 1A), stricture (Fig. 1B), the devel-
opment of columnar metaplasia in place of the normal squamous epithelium (Bar-
retts esophagus) (Fig. 1C), and adenocarcinoma (Fig. 1D). Of particular concern is
the rising incidence of esophageal adenocarcinoma, an epidemiologic trend strongly
linked to the increasing incidence of this condition.4-6 There were about 8000 inci-
dent cases of esophageal adenocarcinoma in the United States in 2004,7 which repre-
sents an increase by a factor of 2 to 6 in disease burden during the past 20 years.8,9
Esophagitis occurs when excessive reflux of acid and pepsin results in necrosis
of surface layers of esophageal mucosa, causing erosions and ulcers. Impaired clear-
ance of the refluxed gastric juice from the esophagus also contributes to damage in
many patients. Whereas some gastroesophageal reflux is normal (and relates to the
ability to belch), several factors may predispose patients to pathologic reflux, includ-
ing hiatus hernia,10,11 lower esophageal sphincter hypotension, loss of esophageal
peristaltic function, abdominal obesity,11,12 increased compliance of the hiatal canal,13
gastric hypersecretory states,14 delayed gastric emptying, and overeating. Often mul-
tiple risk factors are present.
A consistent paradox in gastroesophageal reflux disease is the imperfect corre-
spondence between symptoms attributed to the condition and endoscopic features
of the disease. In a population-based endoscopy study in which 1000 northern Eu-
ropeans were randomly sampled,15 the prevalence of Barretts esophagus was 1.6%,
and that of esophagitis was 15.5%. However, only 40% of subjects who were found
to have Barretts esophagus and one third of those who were found to have esophagi-
tis reported having reflux symptoms. Conversely, two thirds of patients reporting
reflux symptoms had no esophagitis. Furthermore, although gastroesophageal reflux

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 clinical pr actice

is the most common cause of heartburn, other

Table 1. Symptoms and Conditions Associated with Gastroesophageal Reflux
disorders (e.g., achalasia and eosinophilic esopha Disease.
gitis) may also cause or contribute to heartburn.3
Esophageal syndromes

S t r ategie s a nd E v idence Injury (with or without esophageal symptoms)

Reflux esophagitis: necrosis of esophageal epithelium causing erosions or
Diagnosis ulcers at or immediately above the gastroesophageal junction
When symptoms of gastroesophageal reflux dis- Stricture: a persistent luminal narrowing of the esophagus caused by reflux-
ease are typical and the patient responds to ther- induced inflammation
apy, no diagnostic tests are necessary to verify the Barretts esophagus: endoscopically suspected and histologically confirmed
metaplasia in the distal esophagus, usually with the added stipulation
diagnosis.16-18 Rather, the usual reasons prompt- that it be specialized intestinal metaplasia
ing diagnostic testing are to avert misdiagnosis,
Esophageal adenocarcinoma
to identify any complications (including stricture,
Symptoms with or without esophageal injury
Barretts metaplasia, and adenocarcinoma), and to
evaluate treatment failures. Important alternative Common symptoms: heartburn, regurgitation, dysphagia, chest pain
diagnoses to consider include coronary artery dis- Less common symptoms: odynophagia (pain with swallowing), water brash
ease, gallbladder disease, gastric or esophageal (excessive salivation prompted by acid reflux), subxiphoid pain, nausea
cancer, peptic ulcer disease, esophageal motility Extraesophageal syndromes
disorders, and eosinophilic, infectious, or pill Association with gastroesophageal reflux disease established but good evi-
esophagitis. dence for causation only when accompanied by an esophageal syn-
drome
Endoscopy addresses many of these possibili-
ties with the caveat that evaluation for a potential Chronic cough
cardiac cause of the presenting symptoms should Laryngitis (hoarseness, throat clearing): reflux usually a cofactor along with
excessive use of the voice, environmental irritants, and smoking
always be prioritized. Furthermore, the endosco-
pist should have a low threshold for obtaining Asthma (reflux as a cofactor leading to poorly controlled disease)
specimens from esophageal or gastric biopsy to Erosion of dental enamel
detect alternative diagnoses, such as eosinophilic Proposed association with gastroesophageal reflux disease but neither associa-
esophagitis and Helicobacter pylori gastritis. Although tion nor causation established
endoscopy is the primary test in patients whose Pharyngitis
condition is resistant to empirical therapy, its yield Sinusitis
in this setting is low because of the poor correla- Recurrent otitis media
tion between symptoms of gastroesophageal re- Idiopathic pulmonary fibrosis
flux disease and esophagitis, the likelihood that
preexisting esophagitis may have resolved with
previous therapy, and the poor sensitivity for de- the adoption of behaviors to minimize reflux or
tecting motility disorders. Physiological testing is heartburn. Although trials of the clinical efficacy
not routinely needed but can be helpful in selected of dietary or behavioral changes are lacking,20
patients by identifying subtle motility disorders clinical experience suggests that particular pa-
(esophageal manometry), demonstrating abnormal tients may benefit from certain measures.17,18 For
exposure to esophageal acid in the absence of example, patients with sleep disturbance from
esophagitis (ambulatory pH monitoring), or most nighttime heartburn may benefit from elevation
recently, both quantifying exposure to esophageal of the head of the bed, but that recommendation
acid and identifying reflux events regardless of is probably superfluous for a patient without night-
acidic content to assess correlations with symp- time symptoms. Weight reduction should routine-
toms (combined impedancepH monitoring).19 ly be recommended in overweight patients, given
the strong association between an increased body-
Lifestyle Modifications mass index and the likelihood of symptoms.21
Many lifestyle modifications are recommended as
therapy for gastroesophageal reflux disease (Ta- Medication
ble 2). These include the avoidance of foods that Abundant data from randomized trials show ben-
reduce lower esophageal sphincter pressure and efits of inhibiting gastric acid secretion in patients
thus predispose to reflux, the limiting of exposure with gastroesophageal reflux disease (Table 3). Re-
to acidic foods that are inherently irritating, and ducing the acidity of gastric juice ameliorates re-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

clinical trials are lacking with respect to the effi-

A B cacy of double-dose proton-pump inhibitors as a
twice-daily regimen for refractory symptoms, as is
sometimes used in practice.
The response of heartburn to various therapeu-
tic agents is less predictable than that of esophagi-
tis.30 Although, as in the case of esophagitis, trials
suggest that proton-pump inhibitors are superior
to H2-blockers and that both are superior to
placebo for the treatment of heartburn, observed
efficacy rates are lower for heartburn than for
esophagitis and vary widely among studies. This
C D variation is probably due to the heterogeneity of
the study populations and the fact that the out-
come measure in most trials of proton-pump
inhibitors was a complete resolution of symptoms
rather than substantial improvement. The effec-
tiveness of proton-pump inhibitors, as compared
with placebo, for healing esophagitis (typically,
90% vs. 15%) is always greater than that for
complete resolution of heartburn in the same
trials (typically, 40% vs. 15%).
Reflux symptoms tend to be chronic with or
Figure 1. Spectrum of Esophageal Injury in Gastroesophageal Reflux without the presence of esophagitis. Data from
Disease. controlled trials lasting 6 to 12 months showed
Gastroesophageal
ICM
reflux is associated
AUTHOR: Kahrilas with esophagitis caused1stby erosions
RETAKE that continued use of proton-pump inhibitors pre-
of the distal esophageal 2nd
mucosa (Panel A, arrows), distal esophageal
REG F FIGURE: 1 of 1
3rd
stric- vented the recurrence of esophagitis and main-
ture as a consequence
CASE
of chronic erosive esophagitis (Panel
Revised
B, arrows), Bar- tained relief of symptoms (Table 4). An uncon-
retts esophagus with columnar metaplasia
Line of 4-C
the normal squamous epi-
EMail
ARTIST:and
thelium (Panel C, arrows), mst
esophageal
SIZE trolled observational study showed continued
H/T adenocarcinoma
H/T 22p3(Panel D,
Enon
Combo
arrow), shown here in a patient with Barretts esophagus (arrowheads). effectiveness of proton-pump inhibitors in main-
AUTHOR, PLEASE NOTE: taining healing of esophagitis for up to 11 years.31
Figure has been redrawn and type has been reset.
Please check carefully. Thus, a common management strategy is indefi-
flux symptoms and allows esophagitis to heal. nite treatment with proton-pump inhibitors or
Data
JOB: 35916 from several studies ISSUE:
indicate that the likeli-
10-16-08 H2-blockers as necessary to maintain symptom
hood of healing of esophagitis relates directly to control. Adding a dose of an H2-blocker before
the potency of a medications antisecretory effect bedtime to a twice-daily regimen of proton-pump
(Table 4).22-29 In a large meta-analysis of 136 ran- inhibitors has been advocated on the basis of a
domized, controlled trials involving 35,978 patients pharmacodynamic study suggesting additive in-
with esophagitis, the rate of healing among pa- hibition of nocturnal acid secretion.32 However,
tients who were treated with proton-pump inhibi- this practice has not been supported by studies
tors (83%) was greater than that with histamine2- using clinical end points, and other pharmacody-
receptor antagonists (H2-blockers) (52%), and both namic data have shown rapid tachyphylaxis of the
rates were higher than that with placebo (8%).22 effect of H2-blockers.19
In all the trials, antacids were used to treat break- The most common side effects of proton-pump
through symptoms. There were no major differ- inhibitors are headache, diarrhea, constipation,
ences in efficacy noted among various proton-pump and abdominal pain. Although in clinical trials
inhibitors when used in standard doses. The gain these symptoms were not significantly more com-
achieved in esophagitis healing by using twice the mon with proton-pump inhibitors than with pla-
standard dose of a proton-pump inhibitor (as a cebo, they have been confirmed in some patients
once-daily initial dose) was modest but significant: with a testretest strategy. Potential risks of long-
an estimated 25 patients would need to be treated term use of proton-pump inhibitors include sec-
with this regimen to benefit 1 patient.22 Data from ondary hypergastrinemia, malabsorption, and

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 clinical pr actice

hypochlorhydria.33 These risks are mainly theo-

Table 2. Dietary and Lifestyle Recommendations for the Treatment
retical, but large, population-based, epidemiologic of Gastroesophageal Reflux Disease.*
studies have suggested that long-term use of pro-
ton-pump inhibitors was associated with an in- Dietary avoidance
creased risk of hip fracture by a factor of 1.4 in Foods that are acidic or otherwise irritative
subjects over the age of 50 years (presumably at- Citrus fruits
tributable to calcium malabsorption),34 an increase Tomatoes
in the risk of infectious gastroenteritis by a factor Onions
of 1.5,35 and a doubling of the risk of Clostridium
Carbonated beverages
difficile colitis.36 Available agents are categorized
Spicy foods
as either category C (omeprazole) or category B
(H2-blockers and other proton-pump inhibitors) Foods that can cause gastric reflux
for use during pregnancy. Data on hundreds of Fatty or fried foods
accidental exposures to proton-pump inhibitors Coffee, tea, and caffeinated beverages
during pregnancy, as compared with matched con- Chocolate
trols, have shown no appreciable increase in the Mint
risk of birth defects.37 Lifestyle
Smoking cessation
Surgery
Weight reduction for patients who are overweight (BMI, 25.029.9) or obese
Surgery, most commonly Nissen fundoplication, in (BMI, 30.0) or whose onset of symptoms was concurrent with
which the proximal stomach is wrapped around weight gain within the normal range (BMI, 18.524.9)
the distal esophagus to create an antireflux barrier, Reduction in alcohol consumption
is an alternative management approach to chronic Nighttime symptoms
gastroesophageal reflux disease. After the adop-
Avoidance of eating within 3 hr before bedtime
tion of a laparoscopic technique in 1991, the num-
Elevation of head of bed
ber of fundoplications that were performed an-
nually in adults in the United States nearly tripled Postprandial symptoms
by 1999 (to more than 30,000 cases) but has Consumption of smaller and more frequent meals
steadily declined since then.38 Poorer-than-antic- Avoidance of lying down after meals
ipated outcomes, including patient dissatisfaction Abdominal obesity
in community practice, may partially explain this Avoidance of tight garments
trend.39,40
As with therapy with proton-pump inhibitors, * The rationales for proscribed foods and lifestyle modifications are based on
evidence supporting the effectiveness of fundopli- clinical experience or, in some instances, small physiological studies showing
a relevant effect, such as the reduction of lower esophageal sphincter pressure.
cation is stronger for treating esophagitis than for These recommendations should be advocated selectively on the basis of the
treating reflux symptoms. At the 7-year follow-up circumstances of a particular patient. BMI denotes body-mass index, which is cal-
in one study of patients with esophagitis who were culated as the weight in kilograms divided by the square of the height in meters.
randomly assigned to receive either continuous
omeprazole therapy (20 to 60 mg per day) or fun- flatulence,41 an inability to belch,41 and increased
doplication, rates of recurrent esophagitis were bowel symptoms (e.g., diarrhea, bloating, abdomi-
similar between the two groups (10.3% and 11.8%, nal pain, and constipation).44 Reported rates of
respectively).41 In studies in which the assessment reoperation because of disruption or complica-
of symptoms was restricted to the control of heart- tions are as high as 7% within 1 to 3 years.19 Up
burn and acid regurgitation in patients with to 60% of patients who had undergone such sur-
esophagitis, there was significantly improved con- gery continued to use medication for reflux symp-
trol with surgery, as compared with therapy with toms when they were assessed 10 to 12 years after
proton-pump inhibitors.41 However, potential ben- surgery.45 Follow-up of patients who have received
efits of surgery must be weighed against poten- medical therapy, as compared with surgery, have
tial deleterious effects.19,42 These include the in- shown no significant differences in the prevalence
herent risks associated with surgery and the of Barretts esophagus or in the incidence of ad-
frequent need for revision surgery, the risk of se- enocarcinoma (estimated at less than 0.01% per
vere dysphagia (about 6% overall),43 increased year).46-48

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 The n e w e ng l a n d j o u r na l of m e dic i n e

Table 3. Inhibitors of Gastric Acid Secretion Approved for Use by the Food and Drug Administration (FDA).*

Generic Name Brand Name Standard Dose Most Common Side Effects
Histamine2-receptor antagonist Headache, diarrhea, dizziness, fatigue, confusion
Cimetidine Tagamet 400 mg twice daily
Famotidine Pepcid 20 mg twice daily
Nizatidine Axid 150 mg twice daily
Ranitidine Zantac 150 mg twice daily
Proton-pump inhibitor Headache, diarrhea, constipation, abdominal pain
Omeprazole Prilosec 20 mg daily
Pantoprazole Protonix 40 mg daily
Esomeprazole Nexium 40 mg daily
Lansoprazole Prevacid 30 mg daily
Omeprazole with sodium Zegerid 40 mg daily
bicarbonate
Rabeprazole Aciphex 20 mg daily

* With respect to safety during pregnancy or lactation, omeprazole is a category C drug (no adequate studies or adverse
fetal effects in animals). All other drugs are category B drugs (animal studies demonstrate no risk; no human studies).
All doses are those commonly prescribed for histamine-2 receptor antagonists or approved by the FDA for proton-
pump inhibitors in the treatment of esophagitis.
All doses are those commonly prescribed for histamine-2 receptor antagonists or approved by the FDA for proton-
pump inhibitors in the treatment of esophagitis.
The most common side effects (per package inserts and clinical experience) are listed for each therapeutic class, although
none of these effects occurred significantly more frequently with drug than with placebo in controlled clinical trials.
This drug is available in a generic form.
This drug is available over the counter without a prescription.

A r e a s of Uncer ta in t y and adenocarcinoma, potentially allows for early

diagnosis of esophageal carcinoma or even preven-
The optimal criteria are unclear for the diagnosis tion of cancer by ablation of dysplastic lesions. Yet,
of gastroesophageal reflux disease and for the as- despite widespread use of endoscopy for screen-
sessment of whether extraesophageal symptoms, ing for Barretts esophagus, evidence that this
such as laryngitis and chronic cough, are attrib- strategy reduces the rate of death from esophageal
utable to reflux. In addition, there is uncertainty adenocarcinoma is lacking. For such a strategy to
regarding the riskbenefit profile of indefinitely significantly reduce mortality on a population ba-
continuing medication to suppress acid secretion sis, patients with Barretts esophagus must con-
and the optimal degree of acid inhibition. stitute a substantial fraction of those at risk for
Particularly controversial is the appropriate role cancer, reflux symptoms should be predictive of
of endoscopy in screening patients for Barretts finding Barretts esophagus on endoscopy, and the
esophagus and in surveillance of those with detection of Barretts esophagus should improve
known Barretts esophagus.49 The risk of esoph- the clinical outcome.7 However, the above-men-
ageal adenocarcinoma in patients with Barretts tioned population-based data indicate that the
esophagus is 0.50 to 0.75% per year,50 and survival presence of Barretts esophagus was poorly cor-
rates for esophageal adenocarcinoma are substan- related with reflux symptoms.15 Furthermore, in
tially greater among those whose cancers are de- a casecontrol study, more than 40% of patients
tected early (58% for tumors detected in situ, as with esophageal adenocarcinoma reported having
compared with 10% for tumors with regional no antecedent reflux symptoms.4 Similarly, in a
spread at 5 years).51 Thus, screening patients for Kaiser Permanente cohort study, 454 of 589 pa-
Barretts esophagus, followed by surveillance of tients with esophageal adenocarcinoma or adeno-
affected patients for the development of dysplasia carcinoma of the gastric cardia had no identifi-

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 clinical pr actice

able Barretts metaplasia evident in pathological

Table 4. Treatment Data on the Use of Proton-Pump Inhibitors and Histamine2-
specimens, and only 23 of 64 patients who had Receptor Antagonists (H2-Blockers).*
undergone endoscopy before cancer detection had
received the diagnosis of Barretts esophagus.52 Healing of esophagitis
Consistent with these observations, two large sur- Proton-pump inhibitor
veillance programs for Barretts esophagus con- Superior to placebo (83% vs. 18%) at 8 wk; NNTB, 1.722
cluded that even though a small number of inci- Superior to H2-blocker (83% vs. 18%)18; relative risk, 0.5122
dent esophageal adenocarcinomas were detected, Superior to H2-blocker (84% vs. 52%)17; relative risk, 0.512
there was no improvement in survival attributable
Significant doseresponse effect at 4 wk22
to surveillance.53,54 However, these management
Low dose vs. standard dose once daily: NNTB, 10
trials used esophagectomy as the treatment for
high-grade dysplasia or intramucosal cancer with- Standard dose vs. high dose once daily: NNTB, 25
in Barretts esophagus. Current management for H2-blocker
these lesions is shifting rapidly toward less mor- Superior to placebo (41% vs. 20%) at 6 wk; NNTB, 522
bid techniques, such as mucosal ablation and en- No significant doseresponse effect (standard dose vs. high dose twice
doscopic mucosal resection, potentially improving daily)22
outcomes.49 Resolution of heartburn
Esophagitis
Guidel ine s from Profe ssiona l Proton-pump inhibitor superior to placebo (56% vs. 8%) at 4 wk; NNTB,
So cie t ie s 2 to 323
Proton-pump inhibitor superior to H2-blocker (77% vs. 48%) at 4 to 12 wk24
Guidelines for the treatment of gastroesophageal
H2-blocker superior to placebo (56% vs. 45%) at 12 wk25
reflux disease in adults have been published by
the American College of Gastroenterology,16 the No significant doseresponse effect for proton-pump inhibitor at 4 wk22
Canadian Gastroenterology Association,17 and the Low dose vs. standard dose once daily: 75% vs. 79%
American Gastroenterological Association Insti- Standard dose vs. high dose once daily: 73% vs. 76%
tute.18 These guidelines agree closely in cases in Patients without known esophagitis
which the evidence is strongest, most notably in the Proton-pump inhibitor superior to placebo (36.7% vs. 9.5%); NNTB,
use of antisecretory medications to treat esophagi- 3 to 423
tis or heartburn, as summarized in Table 4. Sim- Proton-pump inhibitor superior to H2-blocker (61% vs. 40%); NNTB, 526
ilarly, the guidelines agree that dysphagia should H2-blocker superior to placebo (relative risk, 0.77; 95% CI, 0.60 to 0.99)27
be evaluated with endoscopy. The greatest discrep-
No significant doseresponse effect for H2-blocker at 8 wk
ancy among guidelines is in recommendations for
Standard dose vs. high dose twice daily: 45.8% vs. 44.8%28
or against endoscopy for chronic symptoms of gas-
troesophageal reflux disease with the goal of de- Maintenance therapy
tecting Barretts esophagus and thus reducing the Remission of esophagitis
risk of esophageal adenocarcinoma. The Canadian Proton-pump inhibitor superior to placebo (93% vs. 29%)29
guideline does not advocate screening endoscopy, Low dose of proton-pump inhibitor sufficient in 35 to 95% of patients18
noting that the procedure has not been shown
Remission of heartburn
to reduce mortality from esophageal adenocarci-
Acceptable symptom control with low-dose, intermittent therapy with pro-
noma. The position statement of the American ton-pump inhibitor in 83 to 92% of patients without esophagitis18
Gastroenterological Association Institute concluded
that there was insufficient evidence to recommend * Relative risk refers to the probability of treatment failure in the active-treatment
for or against endoscopy to screen for Barretts group. NNTB denotes number of patients needed to treat to benefit one patient.
Resolution of heartburn is generally defined as no symptoms for 7 days.
esophagus or to diminish the risk of esophageal The duration of maintenance therapy was 6 to 12 months.
adenocarcinoma. In contrast, the American Col-
lege of Gastroenterology recommends consider-
ation of endoscopy in patients with symptoms tient and physician feel early endoscopy to be ap-
suggesting complicated disease (dysphagia, odyn propriate conditions that might encompass
ophagia, bleeding, weight loss, or anemia), those the entire population of patients with gastroesoph-
at risk for Barretts esophagus, or when the pa- ageal reflux disease.

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 The n e w e ng l a n d j o u r na l of m e dic i n e

ma is reduced by any current medical or surgical

c onclusions a nd therapy.46 Patients whose heartburn has not ad-
R ec om mendat ions
equately responded to twice-daily therapy with a
The patient in the vignette reports a history of fre- proton-pump inhibitor should be referred for spe-
quent heartburn consistent with gastroesophageal cialist evaluation. If a patient has symptoms refrac-
reflux disease. Clinical experience suggests that tory to proton-pump inhibitors (especially those
dietary changes may be beneficial if there are ob- attributable to regurgitation) or cannot tolerate
vious dietary precipitants (coffee, chocolate, or fatty such therapy, antireflux surgery may be consid-
foods) and that lifestyle changes are warranted to ered; patients should understand that there are
reduce obesity, smoking, or excessive alcohol use associated risks and that medication is often still
if present. However, lifestyle modification alone needed after surgery.
is unlikely to eliminate his symptoms. It should be recognized that data are limited
I would also recommend therapy with a pro- to guide the use of endoscopy in patients with
ton-pump inhibitor and would anticipate the need gastroesophageal reflux disease. Consistent with
for maintenance therapy, given the patients long current guidelines,15-17 this procedure is routinely
history of symptoms. In this case, after 8 to 12 recommended for patients with odynophagia, gas-
weeks of a standard dose of a proton-pump in- trointestinal blood loss, anemia, or dysphagia.
hibitor, I would advise the patient to titrate the A patients anxiety and preference to undergo the
dose to find the lowest dose that provides satis- procedure may also be an indication. The ques-
factory control of heartburn. A reasonable target tion of whether to screen other patients remains
is 80% symptom relief; patients often continue to controversial, with various professional societies
have symptoms triggered by overindulgence. Oc- providing conflicting opinions. I do not routinely
casional breakthrough symptoms can be treated recommend endoscopy in patients without these
with antacids as necessary. Although proton-pump indications, given the low absolute risk of esoph-
inhibitors are more effective in general than H2- ageal cancer in patients with gastroesophageal
blockers, the latter will suffice for some patients, reflux disease and the lack of data to show that
and some will find as-needed therapy to be suf- endoscopic screening results in better outcomes.
ficient. Other patients will require twice-daily Supported by a grant (R01 DC00646) from the Public Health
therapy with a proton-pump inhibitor; in such Service.
Dr. Kahrilas reports receiving consulting fees from AstraZen-
cases, medication should be taken 30 to 60 min- eca, Procter & Gamble, and Xenoport. No other potential con-
utes before breakfast and dinner. There is no evi- flict of interest relevant to this article was reported.
dence that the risk of esophageal adenocarcino- An audio version of this article is available at www.nejm.org.

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