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com       World J Gastroenterol 2009 February 28; 15(8): 990-995

wjg@wjgnet.com World Journal of Gastroenterology ISSN 1007-9327
doi:10.3748/wjg.15.990 © 2009 The WJG Press and Baishideng. All rights reserved.

BRIEF ARTICLES

Comparative study of omeprazole, lansoprazole,

pantoprazole and esomeprazole for symptom relief in
patients with reflux esophagitis

Ri-Nan Zheng

Ri-Nan Zheng, Hainan Medical College, 31 Longhua Road, Key words: Omeprazole; Pantoprazole; Lansoprazole;
Haikou 57102, Hainan Proince, China Esomeprazole; Reflux esophagitis; Symptom relief
Author contributions: Zheng RN wrote the paper.
Correspondence to: Ri-Nan Zheng, Hainan Medical College, Peer reviewer: Radha K Dhiman, Associate Professor,
31 Longhua Road, Haikou 57102, Hainan, Department of Hepatology, Postgraduate Institute of Medical
China. zhengrinan1964@yahoo.com.cn Education and Research, Chandigarh 160012, India
Telephone: +86-898-66528102
Received: November 17, 2008 Revised: December 25, 2008 Zheng RN. Comparative study of omeprazole, lansoprazole,
Accepted: December 31, 2008
pantoprazole and esomeprazole for symptom relief in pa-
Published online: February 28, 2009
tients with reflux esophagitis. World J Gastroenterol 2009;
15(8): 990-995 Available from: URL: http://www.wjgnet.
com/1007-9327/15/990.asp DOI: http://dx.doi.org/10.3748/
wjg.15.990
Abstract
AIM: To clarify whether there is any difference in the
symptom relief in patients with reflux esophagitis fol-
lowing the administration of four Proton pump inhibi- INTRODUCTION
tors (PPIs).
Gastroesophageal reflux disease (GERD) is a common
METHODS: Two hundred and seventy-four patients disorder with a high incidence rate of 10%-38% in the
with erosive reflux esophagitis were randomized to Western population occurring at least once a week[1,2].
receive 8 wk of 20 mg omeprazole (n = 68), 30 mg The prevalence of GERD has been increasing[3].
of lansoprazole (n = 69), 40 mg of pantoprazole (n The severity of GERD is directly correlated with the
= 69), 40 mg of esomeprazole (n = 68) once a day degree and duration of esophageal acid exposure and is
in the morning. Daily changes in heartburn and acid highly pH dependent[4-6]. Chronic exposure is associated
reflux symptoms in the first 7 d of administration were with serious complications including esophageal stricture
assessed using a six-point scale (0: none; 1: mild; 2: in 4%-20% of patients[4] and Barrett’s esophagus in up
mild-moderate; 3: moderate; 4: moderate-severe; 5: to 15% of patients with GERD[4-7].
severe). Healing of reflux esophagitis is directly correlated
with the intragastric pH > 4.0 [8,9] . The efficacy of
RESULTS: The mean heartburn score in patients antisecretory drugs in healing reflux esophagitis depends
treated with esomeprazole more rapidly decreased on the strength and duration of acid suppression within
than those receiving other PPIs. Complete resolution of a 24 h period, and the duration of the treatment [10].
heartburn was also more rapid in patients treated with Proton pump inhibitor (PPI) therapy is effective for
esomeprazole for 5 d compared with omeprazole (P = acid-related symptoms. A number of investigators
0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, have reported that earlier symptom relief and higher
respectively), lansoprazole (P = 0.0020, P = 0.0046, P
endoscopic healing rates have been obtained with PPI in
= 0.0037, P = 0.0016, P = 0.0076, respectively), and
comparison with H2-receptor antagonists (H2-RAs)[11,12].
pantoprazole (P = 0.0006, P = 0.0005, P = 0.0009, P =
The time period required to obtain maximal inhibition
0.0031, P = 0.0119, respectively). There were no sig-
nificant differences between the four groups in the rate
of gastric acid secretion is, however, reported to differ
of endoscopic healing of reflux esophagitis at week 8. between PPI [13-17]. The time taken for the resolution
of symptoms in patients with reflux esophagitis is,
CONCLUSION: Esomeprazole may be more effective therefore, unlikely to be uniform in all PPI. As the
than omeprazole, lansoprazole, and pantoprazole for quality of life (QOL) of patients with reflux esophagitis
the rapid relief of heartburn symptoms and acid reflux is decreased by heartburn symptoms[18,19], quick symptom
symptoms in patients with reflux esophagitis. relief is important to normalize their QOL. It has not
hitherto been fully determined whether differences in
© 2009 The WJG Press and Baishideng. All rights reserved. the onset of anti-secretary activity may affect the speed

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 Zheng RN. Drug therapy of gastroesophageal reflux disease   991

of symptom relief with different PPI. In this study, we (heartburn and acid reflux) were separately analyzed.
investigated the differences in symptom relief in the The primary endpoint of the present study was to clarify
first 7 d of administration of omeprazole, lansoprazole, whether rapid symptom relief in the first week of drug
pantoprazole, and esomeprazole in patients with reflux administration differed between the four kinds of PPI.
esophagitis.
Statistical analysis
Statistical analysis of inter-group data was performed
MATERIALS AND METHODS using the Microsoft Office Excel F-test. The Microsoft
Two h u n d r e d a n d s e ve n t y - f o u r p a t i e n t s w i t h Office Excel F-test was also used to compare the
endoscopically proven reflux esophagitis in the Affiliated complete disappearance of symptoms between the
Hospital of Yanbian University from January, 2006 to groups. In addition, sex, age, H pylori status and grading
September, 2007 and the Affiliated Hospital of Hainan of endoscopic esophagitis were analyzed by c2 test.
Medical College from October, 2007 to November, 2008
were included in the study. Ten of the patients were lost
to follow-up, who refused endoscopic examination after RESULTS
administration of PPI. Subjects with active peptic ulcer, There were no significant differences between the
upper gastrointestinal cancers, malignant diseases of groups in sex, age, H pylori status, the grade of reflux
other organs, severe cardiac, hepatic, or renal diseases, esophagitis, and the proportion of cases with heartburn
anemia (hemoglobin concentration < 10 g/dL), or and acid reflux symptoms before the administration of
who were pregnant and/or lactating, were excluded. the drugs (Table 1).
After written informed consent for enrollment in this No severe side effects related to PPI administration
study was obtained, one of four PPI (omeprazole, were reported in subjects participating in the present
lansoprazole, pantoprazole, or esomeprazole, which study. None of the patients needed to take antacids for
were contained in sealed envelopes) was administrated the relief of symptoms after PPI administration.
for 8 wk (Figure 1). The sealed envelopes containing one Figures 2 and 3 show the daily changes in the mean
of four PPI were randomly assigned for administration. symptom scores of heartburn and acid reflux in all
Each PPI was administered once in the morning, 20 mg patients with each PPI. Although there were no differ-
omeprazole, 40 mg pantoprazole, 30 mg lansoprazole, ences between the groups in the heartburn score before
and 40 mg esomeprazole. Subjects were not permitted to PPI administration, the heartburn score was signifi-
take H2-RAs or prokinetic drugs during the study period. cantly lower in subjects administered esomeprazole after
There were 135 men and 139 women (mean age 57.8 ± the first and second days than in those administered
13.5 years, range 36-85 years). omeprazole (P = 0.0031, P = 0.0092), lansoprazole (P =
All endoscopic examinations were perfor med 0.0039, P = 0.0088), and pantoprazole (P = 0.0009, P =
by one endoscopist, using a high-resolution upper 0.0036), respectively. This difference between subjects
gastrointestinal endoscope (GIF 260 series; Olympus, administered esomeprazole and the other PPI tended to
Tokyo, Japan) before and 8 wk after the administration disappear after 5 d of administration of the test drugs.
of PPI. Endoscopic diagnosis and the grading of No significant differences in acid reflux scores were seen
reflux esophagitis were based on the Los Angeles (LA) between the groups (Figure 3).
classification [20]. Helicobacter pylori (H pylori) infection When the analysis was limited to only the patients
status was also tested by measuring serum anti-H pylori who initially reported heartburn and acid reflux, the
immunoglobulin IgG antibodies, using an ELISA test heartburn score of those subjects administered esome-
(Institute of Immunology, Tokyo, Japan). prazole decreased more quickly than those administered
All patients were asked to keep a symptom diary, omeprazole, lansoprazole, and pantoprazole (Figure 4).
in which they recorded the severity of symptoms This difference also tended to disappear after 5 d of ad-
(heartburn and acid reflux) prior to and during the first ministration of the test drugs. Complete disappearance
7 d of PPI administration. The severity of symptoms of heartburn symptoms after administration of the test
was graded on a six-point scale (0: none; 1: mild; 2: drugs from 1 d to 5 d occurred more rapidly in subjects
mild-moderate; 3: moderate; 4: moderate-severe; 5: administered esomeprazole than in those administered
severe and/or intolerable) and was recorded daily. Mild omeprazole (P = 0.0018, P = 0.0098, P = 0.0027, P =
symptoms were defined as a heartburn/acid reflux 0.0137, P = 0.0069, respectively), pantoprazole (P =
that did not disturb the normal daily activity of the 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119,
patients. Moderate symptoms were defined as those respectively), and lansoprazole (P = 0.0020, P = 0.0046,
that bothered the daily activity, while the patients P = 0.0037, P = 0.0016, P = 0.0076, respectively). No
continued to work productively. Severe symptoms were significant differences in acid reflux scores were seen be-
defined as high-grade symptoms that stopped the daily tween the groups (Figure 5).
productive activity of the patients. The patients were Ten of the 274 subjects enrolled in the present study
instructed to record the severity of their symptoms as refused endoscopic examination after administration of
a whole previous day’s score in the following morning. PPI, so upper gastrointestinal endoscopy was performed
The daily changes in the severity of two symptoms in 264 patients at week 8 after the commencement of

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 992 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol  February 28, 2009 Volume 15 Number 8

Table 1 Characteristics of subjects

Omeprazole (n = 68) Lansoprazole (n = 69) pantoprazole (n = 69) Esomeprazole (n = 68) Statistical difference
Sex (male/female) 33/35 35/34 34/35 33/35 NS
Age (mean ± SD) (yr) 57.9 ± 14.1 58.1 ± 13.0 57.8 ± 13.2 57.4 ± 12.8 NS
H pylori (positive/negative) 29/39 31/38 30/39 29/39 NS
Endoscopic esophagitis
(Los Angeles classification)
A 20 20 20 20 NS
B 26 26 28 26 NS
C 20 21 20 20 NS
D 2 2 1 2 NS
Symptoms
Heartburn (%) 61 (89.7) 63 (91.3) 62 (89.9) 63 (92.6) NS
Acid reflux (%) 33 (48.5) 35 (50.7) 34 (49.3) 35 (51.5) NS
No symptom (%) 8 (11.8) 5 (7.2) 8 (11.5) 5 (7.4) NS

NS: Not significant.

Eligible patients with endoscopically

proven reflux esophagitis (n = 274)

Entry and randomization by envelope method (n = 274)

Omeprazole (n = 68) Lansoprazole (n = 69) Pantoprazole (n = 69) Esomeprazole (n = 68)

Lost to follow up (n = 0) Lost to follow up (n = 0) Lost to follow up (n = 0) Lost to follow up (n = 0)

Analysis of daily symptoms for Analysis of daily symptoms for Analysis of daily symptoms for Analysis of daily symptoms for
1 wk (n = 68) 1 wk (n = 69) 1 wk (n = 69) 1 wk (n = 68)

Lost to follow up (n = 3) Lost to follow up (n = 2) Lost to follow up (n = 2) Lost to follow up (n = 3)

Analysis of endoscopic healing Analysis of endoscopic healing Analysis of endoscopic healing Analysis of endoscopic healing
after 8 wk (n = 65) after 8 wk (n = 67) after 8 wk (n = 67) after 8 wk (n = 65)

Figure 1 Study protocol.

drugs. These patients had taken all of the PPI. The en- in the complete disappearance of heartburn between
doscopic healing rates for reflux esophagitis in subjects H pylori-positive and H pylori-negative patients (Figure 7).
administered omeprazole, lansoprazole, pantoprazole The daily changes in the acid reflux score during the
and esomeprazole were 87.7%, 89.6%, 91.1% and first week of administration of the test drugs also did
95.4%, respectively. Although the healing rate in subjects not differ between H pylori-positive and H pylori-negative
administered esomeprazole tended to be higher than in patients (data not shown).
those administered omeprazole, lansoprazole and panto-
prazole, the differences did not reach statistically signifi-
cant levels. DISCUSSION
When the patients were divided into H pylori positive Gastroesophageal reflux disease (GERD) is caused by
and negative groups, the healing rate for reflux esopha- acid reflux, which can be treated by suppressing gastric
gitis at week 8 in H pylori positive patients tended to be acid secretion[21,22]. The efficacy of antisecretory drugs
higher than that in negative subjects (92.4% vs 85.8%, in healing reflux esophagitis depends on the potency
P > 0.05, χ2 =2.95, by χ2 test). of acid suppression[12], and PPIs are considered to be
The daily changes in heartburn score during the first the most effective drugs for reflux esophagitis[23]. The
week of administration of the test drugs did not differ symptoms of reflux esophagitis, such as heartburn, have
between H pylori-positive and H pylori-negative patients been demonstrated to markedly impair QOL in these
by F-test (Figure 6). There was no significant difference patients[18,19]. Complete and rapid relief of symptoms

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 Zheng RN. Drug therapy of gastroesophageal reflux disease   993

3.5 4.00

3.0

3.00
2.5

2.0
Score

Score
2.00 ☆※◎ 1
●※○
1.5
☆※◎ 2
◇☆◎
1.0 ☆※◎ 3
1.00
☆※◎ 4 ☆※◎ 5
0.5

0.0 0.00
Before 1 2 3 4 5 6 7 d Before 1 2 3 4 5 6 7 d

After drug administration After drug administration

Figure 2 Daily changes in mean heartburn score for all subjects on each Figure 4 Daily changes in mean heartburn score for all subjects on each
proton pump inhibitor regimen. (◆) Subjects administered omeprazole proton pump inhibitor regimen, considering only subjects with symptoms
(n = 68), (■) Subjects administered lansoprazole (n = 69), (▲) Subjects prior to commencement of test-drug administration. ( ◆ ) Subjects
administered pantoprazole (n = 69), (●) Subjects administered esomeprazole administered omeprazole (n = 61), (■) Subjects administered lansoprazole
(n = 68). ◇☆◎ Significant difference between the omeprazole, lansoprazole, (n = 63), (▲) Subjects administered pantoprazole (n = 62), (●) Subjects
pantoprazole, and esomeprazole after 1 d drug administration (P = 0.0031, administered esomeprazole (n = 63). ☆※◎△ 1-5 significant difference between
0.0039, 0.0009, respectively). ●※○ significant difference between the the omeprazole, lansoprazole, pantoprazole and esomeprazole after 1-5 d drug
omeprazole, lansoprazole, pantoprazole and esomeprazole after 2 d drug administration, P = 0.0018, 0.0020, 0.0006, respectively, P = 0.0098, 0.0046,
administration (P = 0.0092, 0.0088, 0.0036, respectively). 0.0005, respectively, P = 0.0027, 0.0037, 0.0009, respectively, P = 0.0137,
0.0016, 0.0031, respectively, P = 0.0069, 0.0076, 0.0119, respectively.

1.5
3.0

2.5
1.0
2.0
Score

Score

1.5
0.5
1.0

0.5
0.0
Before 1 2 3 4 5 6 7 d 0.0
Before 1 2 3 4 5 6 7 d
After drug administration
After drug administration
Figure 3 Daily changes in mean acid regurgitation score for all subjects
on each proton pump inhibitor regimen. There were no significant Figure 5 Daily changes in mean acid regurgitation score for considering
differences between the (◆) omeprazole (n = 68), (■) lansoprazole (n = 69), only subjects with symptoms prior to commencement of test drug
(▲) pantoprazole (n = 69), and (●) esomeprazole (n = 68) groups after drug administration. There were no significant differences between the ( ◆ )
administration. omeprazole (n = 33), (■) lansoprazole (n = 35), (▲) pantoprazole (n = 34),
and (●) esomeprazole (n = 35) groups after drug administration.

is, therefore, of critical importance in the treatment of

patients with reflux disease. of heartburn symptoms during the first day and the first
In the present study, we compared with efficacy of 5 d after the commencement of administration.
omeprazole, pantoprazole, lansoprazole and esomeprazole In the present study, we demonstrated that esome-
for symptom relief in the first 7 d of treatment for reflux prazole gave faster symptom relief than pantoprazole,
esophagitis. The administration of esomeprazole was most lansoprazole and omeprazole. Because esomeprazole has
effective for symptom relief within 2 d compared with been shown to have a faster onset of antisecretory activity
omeprazole, lansoprazole and pantoprazole administration, than omeprazole, lansoprazole and pantoprazole[24,27],
this difference disappeared 5 d after commencement of esomeprazole rapidly increased the detectable intragastric
drug administration. The results of present study are pH > 4 on the first treatment day[26], and the first 5 d after
consistent with those of the study by Rohss et al[24-26] and commencement of administration of esomeprazole, and
Miner et al[27], who reported that esomeprazole 40 mg the intragastric pH > 4 maintained for a longer period of
daily was more effective than omeprazole 20 mg daily, time than lansoprazole, pantoprazole and omeprazole[25,27].
lansoprazole 30 mg, pantoprazole 40 mg daily in the relief A l t h o u g h t h e s y m p t o m r e l i e f wa s f a s t e r by

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 994 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol  February 28, 2009 Volume 15 Number 8

3 4

3
2
Score

Score
2

1
1

0 0
Before 1 2 3 4 5 6 7 d Before 1 2 3 4 5 6 7 d

After drug administration After drug administration

Figure 6 Daily changes in mean heartburn score in H pylori-positive and Figure 7 Daily changes in mean heartburn score in H pylori-positive and
-negative of all subjects with test drug administration. (●) H pylori-negative -negative subjects with heartburn prior to test drug administration. (▲)
subjects (n = 155), (■) H pylori-positive subjects (n = 119), There was no H pylori-negative subjects (n = 140), (●) H pylori-positive subjects (n = 109),
significant difference between H pylori-positive and H pylori-negative subjects There was no significant difference between H pylori-positive and H pylori-
after test drug administration. negative subjects after test drug administration.

administration of esomeprazole than by omeprazole, daily or lansoprazole 30 mg daily for the rapid relief of
pantoprazole or lansoprazole, the four kinds of PPI heartburn symptoms in patients with endoscopically
investigated in the present study were demonstrated to proven reflux esophagitis. Symptom relief after several
be effective for symptom relief within 1 wk in patients days of treatment and reflux esophagitis healing rates
with endoscopically proven esophagitis. Recently, PPI after 8 wk of treatment, were not different between
has been also used for the diagnosis of gastroesophageal patients treated with omeprazole, pantoprazole,
reflux, not only in the patients with non-erosive reflux lansoprazole, or esomeprazole.
disease (NERD)[28,29], but also in patients with atypical
gastroesophageal reflux symptoms [30,31]. The present
study suggests that the four kinds of PPI are effective COMMENTS
COMMENTS
for the diagnosis of the existence of gastroesophageal Background
acid reflux, and it may be worthwhile investigating In patients with gastroesophageal reflux disease (GERD), esomeprazole has
whether esomeprazole could shorten the time period demonstrated pharmacological and clinical benefits beyond those seen with the
other proton pump inhibitors (PPIs ). The efficacy of omeprazole, lansoprazole
necessary for diagnosis.
and esomeprazole for symptom relief in the first 7 d of treatment for reflux
The healing rate of reflux esophagitis after 8 wk of esophagitis was compared with endoscopic healing rates for reflux esophagitis
treatment tended to be higher in patients administered after 8 wk of treatment.
esomeprazole than in those administered omeprazole, Innovations and breakthroughs
lansoprazole or pantoprazole, although these differences Although many investigators have reported that esomeprazole can more rapidly
did not reach a statistically significant level. However, increase detectable intragastric pH > 4 on the first treatment day, and the first
these differences need to be confirmed by further large 5 d than the other PPIs, symptom relief after administration of the lansoprazole,
pantoprazole, omeprazole and esomeprazole has not been investigated.
comparative studies, which may have been caused by This paper showed for the first time that symptom relieved in patients with
variations in the proportion of H pylori positive patients GERD after administration of the lansoprazole, pantoprazole, omeprazole
between the four PPI regimen groups, because H pylori and esomeprazole. Esomeprazole more rapidly relieved heartburn after
infection has been reported to influence the healing of administration of the test drugs than the other PPIs.
reflux esophagitis by PPI[32]. The degree of symptom Peer review
relief was not, however, different during the first week This is a report designed to analyze a symptom relief for GERD subjects based
on presenting symptoms and endoscopic healing rate for reflux esophagitis in
of administration of PPI between H pylori positive and China. This clinical study was well designed and the manuscript is well written.
negative patients. The symptomatic response to PPI
treatment during the first week administration should
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