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Aliment Pharmacol Ther 1998; 12: 355±360.

Omeprazole and sucralfate in the treatment of NSAID-induced
gastric and duodenal ulcer
G. BIANCHI POR RO, M. LAZZARONI, G. MAN ZIONN A & M. PETRILLO
Gastrointestinal Unit, L Sacco University Hospital, Milan, Italy
Accepted for publication 4 December 1997

SUMMARY

Aim: To establish the healing ef®cacy of two drugs,
omeprazole and sucralfate, when given to patients who
had developed gastric or duodenal ulcer while
undergoing chronic treatment with non-steroidal antiin¯ammatory drugs (NSAIDs).
Methods: Ninety-eight patients with arthritis or arthrosis
and NSAID-related gastric or duodenal ulcer were
admitted to the endoscopic, single-blind study. They
were randomized to receive either omeprazole 20 mg
o.m. or sucralfate 2 g b.d. for 4±8 weeks. The patients
continued to receive the same NSAID during the trial.
Upper gastrointestinal endoscopy was performed at
entry and after 4 or 8 weeks.
Results: Eighty-eight patients completed the 4-week
study, but only 81 were available for ®nal analysis at
8 weeks. Omeprazole was signi®cantly superior to

INTRODUCTION

Gastroduodenal mucosal damage is known to be the
main undesirable side-effect of treatment with nonsteroidal anti-in¯ammatory drugs. Mucosal erosions or
ulcers have been reported in more than 30% of patients
taking NSAIDs while dyspepsia occurs in up to 60%.1, 2
The problem may sometimes be so serious as to call for
suspension of NSAID treatment,3 with negative effects
on the state of the underlying disease. Relatively few
and sometimes con¯icting data are available at present4±10 regarding the role of gastric mucosal cytopro-

Correspondence to: Prof. G. Bianchi Porro, Gastrointestinal Unit, L. Sacco
University Hospital, Via GB Grassi, 74, 20157 Milan, Italy.
Ó 1998 Blackwell Science Ltd

sucralfate in inducing gastric ulcer healing after both
4 (87 vs. 52%, P ˆ 0.007) and 8 weeks (100 vs. 82%,
P ˆ 0.04). No statistically signi®cant difference in
duodenal ulcer healing rates emerged between the two
groups either at 4 (79 vs. 55%) or 8 weeks (95 vs.
73%). The healing rates in patients with combined
gastric and duodenal ulcer were 67 vs. 33% after
4 weeks and 67 vs. 67% after 8 weeks of treatment. The
percentages of asymptomatic patients were similar in
the two treatment groups both at 4 (70 vs. 73%) and
8 weeks (70 vs. 75%). H. pylori infection did not
in¯uence healing rates, but signi®cantly more
H. pylori-positive patients healed with omeprazole.
Conclusions: The results of this study show that
omeprazole is superior to sucralfate in healing NSAIDinduced gastroduodenal ulcer in patients who continue
to take anti-in¯ammatory drugs. The good results
observed were unrelated to H. pylori status.

tective agents or antisecretory drugs in the treatment of
NSAID-related gastroduodenal ulcers.
The aim of our study was to evaluate the healing and
analgesic effect of omeprazole compared to a cytoprotective agent, sucralfate, in arthritic patients with
NSAID-induced gastroduodenal ulcers where it was
not possible to suspend the offending drug.
METHODS

Patients
During recent years, in collaboration with the Rheumatology Unit of our hospital, we have implemented a
programme of endoscopic evaluation of NSAID-induced
gastroduodenal lesions in patients suffering from
355

and prevalence of ulcer symptoms. Helicobacter pylori status A serum sample was obtained from each patient at entry for evaluation of IgG antibody to H. moderate or severe. according to a single-blind protocol. heartburn. and Student's t-test. All endoscopies were performed by the same physician (G. and these were graded as none. All patients were found to be completely normal at basal endoscopy. alcohol) during the treatment period. number of gastric or duodenal ulcers or both. Demographic and clinical characteristics of the patients entered into the trial (no signi®cant differences between groups) Omeprazole (n ˆ 50) Sucralfate (n ˆ 48) Age (years) (mean and range) Male/female Smoking Yes No 56. The study end-point was reached if complete reepithelialization of the ulcer crater occurred. In particular. Patients in both groups were comparable as to age. Table 1. pylori. nausea and vomiting.5 ‹ 22 years) were recruited for the trial. H. by means of a ¯uorescence enzyme-immunoassay test. were submitted to upper GI endoscopy. before starting NSAID treatment. but later presented gastric or duodenal ulcer or both during treatment with NSAIDs. where indicated. mean age 55.m. While continuing the offending drug at the same dosage. pylori infection was present in 35/59 (59%) of subjects with gastric ulcer. Study design All patients gave their informed consent and the study was approved by the local Ethical Committee. A past history of peptic ulcer was observed in 30% of the patients while H. or osteoarthritis. who were candidates for long-term treatment with NSAIDs. sex.7 (25±75) 9/39 11 37 Alcohol Yes No 22 28 24 24 Coffee Yes No Arthritis (number of patients) Arthrosis (number of patients) GU DU GU + DU Ulcer symptoms present/absent 41 9 43 7 27 20 3 29/21 41 7 37 11 32 13 3 25/23 Ó 1998 Blackwell Science Ltd. mild. Further endoscopic controls were repeated after 3 and 6 months in asymptomatic cases or sooner in the event of the onset of painful dyspepsia and/or complications. The endoscopist was unaware of the drugs being taken. Endoscopy was performed after 4 or 8 weeks or in the event of complications or antacid-resistant painful dyspepsia. 355±360 . to omeprazole 20 mg o. Table 2 lists the various NSAIDs used speci®cally for rheumatological treatment and the corresponding numbers of gastric or duodenal ulcers that were induced. An ulcer was de®ned as an excavated mucosal break of 5 mm or more in diameter. Aliment Pharmacol Ther 12. with the fully open spoon equivalent to 5 mm. smoking and drinking habits. Patients who had taken anti-ulcer drugs in the last 6 months or were taking anticoagulant or prednisone >10 mg/day were also excluded.P). Patients were invited not to change their usual dietary or other habits (smoking.3 (25±77) 14/36 9 41 54.B. rheumatoid arthritis.d. recent acute upper gastrointestinal bleeding and severe renal impairment. The size of the population entered in the study was calculated assuming that the healing rate after omeprazole is superior by at least 30% to that oberved with sucralfate and considering a signi®cant difference (a ˆ 0.01) with a power (b) of 75%. Patients were excluded if they had gastric surgery.356 G. (n ˆ 50) or sucralfate 2 g b. Statistical analysis The differences between the two treatment groups were compared statistically by means of the v2 test. Ulcer dimensions were measured using standard Olympus biopsy forceps. type of arthritic condition. 23 males. gastrointestinal malignancy. All patients. the patients were randomized. (n ˆ 48). and in none of the six patients with both gastric and duodenal ulcer. pylori infection was present in 56/98 (57%) of the cases. 95% con®dence intervals for the difference in the healing rate percentage were also calculated. Ninety-eight consecutive patients (75 females. Fisher's exact test. RESULTS Table 1 shows the demographic and clinical characteristics of the patients at entry. The following dyspeptic symptoms were evaluated at each visit: epigastric pain. BIANCHI PORRO et al. in 21/33 (64%) of those who developed a duodenal ulcer.

When gastric ulcers were considered separately. 355±360 The appearance of gastric or duodenal ulcer is a fairly frequent event during chronic NSAID therapy. we compared the . respectively) and after 8 weeks of treatment (70 vs. pylori status. Cumulative number of dropouts and medical reasons for withdrawal from the study. while ®ve failed to return for non-medical reasons. healing was observed in 20/23 (87%) of those treated with omeprazole compared to 15/29 (52%) of those treated with sucralfate (P ˆ 0. The clinical-endoscopic outcome according to treatment is reported in Table 3. No signi®cant differences were observed between the two groups as regards healing rates in DU patients (79 vs. the healing rates in the population as a whole rose to 96% (43/45 patients) in the omeprazole group vs. 78% (28/36 patients) in the sucralfate group (P ˆ 0. duodenal ulcers (DU) and combined gastric and duodenal ulcers (GU + DU). Type of NSAIDs received by patients participating in the study and number of peptic ulcers developed following administration of each drug GU DU GU + DU Aspirin Indomethacin Piroxicam Tenoxicam Ketoprofen Naproxen Sulindac Diclofenac Sulindac + diclofenac NSAIDs + steroids 1 5 7 2 2 12 2 11 2 15 Ð 7 4 Ð 1 5 2 4 Ð 10 Ð 1 1 Ð Ð 1 Ð 1 Ð 2 Total 59 33 6 Eighty-eight out of 98 patients completed the study at 4 weeks. Five patients in the omeprazole group and three in the sucralfate group were withdrawn for nonmedical reasons. after 4 weeks 37/45 patients (82%) in the omeprazole group were healed compared to 22/43 (51%) of those in the sucralfate group (P ˆ 0. SUC RALFATE FOR NSAID-INDUCED ULCERS Table 2. Table 4 shows the healing rates of combined gastric and duodenal ulcers according to H. 71%) only in H. omeprazole proved comparable to sucralfate in inducing symptom relief in healed patients. The healing rates in patients with both DU and GU were. Reports in the literature have already shown that it is possible to achieve healing of NSAID-induced ulcers whilst continuing anti-in¯ammatory treatment. 75%.004). The percentage of healing in both DU and GU patients was 67%. respectively. After 8 weeks.4±10 In the present controlled study. however. 73%. Ó 1998 Blackwell Science Ltd. such a policy is not always possible. While this practice may speed up the healing of mucosal lesions. pylori-positive patients. 55%). 81%. 67% and 33%. Aliment Pharmacol Ther 12. DISCUSSION Figure 1. the standard policy has been to interrupt anti-in¯ammatory therapy.04). when faced with NSAID-induced ulcers.007). two patients in the sucralfate group interrupted the anti-ulcer treatment due to the onset of vomiting. respectively).1.01) Omeprazole again proved signi®cantly superior to sucralfate in healing GU (100 vs. two patients in the sucralfate group stopped taking NSAIDs due to epigastric pain. After 8 weeks of treatment.OMEPRAZOLE VS. both at 4 weeks (70 vs. omeprazole proved signi®cantly more effective than sucralfate both at 4 (81 vs. 48% of patients healed) and 8 weeks (96 vs. Regarding the analgesic effect. whereas there was no statistically signi®cant difference between the two groups as regards DU (95 vs. 73%). 11 and so is the risk of serious complications. The 8-week study was thus completed by 81 patients: 45 in the omeprazole group and 36 in the sucralfate group (Figure 1). P ˆ 0. The two groups of treatment showed no difference in success percentages between infected and uninfected patients. Considering the total 357 population of gastric ulcers (GU).12±14 In clinical practice.

The role of cytoprotective drugs such as sucralfate15 is less well de®ned. IC95 58. gastric erosions were also included.18 Unlike that observed with standard doses of H2-antagonists.0 respective capacities of omeprazole and sucralfate to heal NSAID-induced ulcers in rheumatic patients continuing NSAIDs at the same dosage which initially caused the ulcer. 10 who showed that.2 + 45.05 CI95 + 4. CI95 ) 0. BIANCHI PORRO et al.9 & 32.5 compared sucralfate 1 g q. pylori status * P < 0.05.4 & 49.d..3) Healed DU 15/19 (79%) 6/11 (54.16 To the contrary. Manniche et al. with ranitidine 150 mg b.4 15/29 (52%) 1/3 (34%) 16/22 (73%) Healing at 4 weeks Healing at 8 weeks HP+ HP) HP+ HP) 22/27 (81%)* 12/25 (48%)* 15/18 (83%)  10/18 (56%)  26/27 (96%)à 15/21 (71%)à 17/18 (94%)§ 13/15 (87%)§ 2/3 (66%) 21/28 (75%) Table 4.04.6) Healed GU 20/23 (87%) ((P ˆ 0. There was no statistically signi®cant difference in ulcer healing rates in patients who stopped NSAID treatment compared with those who continued. in this experience.01. However. Per cent of healing according to type of treatment and H.5%) (P ˆ N.21 Ó 1998 Blackwell Science Ltd.9   N.S.004.7 a more potent acid inhibition obtained with proton pump inhibitors or with high doses of famotidine19 appears to overcome the negative interaction of NSAIDs with the proliferative responses at the ulcer margin and speed up the healing of both gastric and duodenal ulcers. Similar 9-week healing rates were reported with sucralfate (83%) and ranitidine (84%). in rheumatic patients with gastric or duodenal ulcers. CI95 + 9. the trend favouring the proton pump inhibitor is indicative. This observation was con®rmed by Hawkey and co-workers9.d. IC95 12. In the clinical setting the positive role of omeprazole was ®rst suggested by Walan et al. the proton pump inhibitor 20± 40 mg daily is better than misoprostol 800 lg daily for healing and prevention of duodenal ulcers and is superior to ranitidine 300 mg daily for healing and prevention of both gastric and duodenal ulcers.0) 23/23 (100%) 18/22 (82%) (P ˆ 0. for which recent experimental observations suggest a cause other than acid. This observation was con®rmed in another small study which showed an improvement in the gastric lesion score.4 + 28.5 à P < 0.1) 18/19 (95%) 8/11 (73%) (P ˆ N.s. but not statistically signi®cant.S. 355±360 . in NSAID users.2) Healed GU + DU Asymptomatic healed patients 2/3 (66%) 26/37 (70%) 2/3 (66%) 30/43 (70%) Omeprazole Sucralfate 12.9 + 56.7) 43/45 (96%) 28/36 (78%) (P ˆ 0. a controlled study in 60 patients receiving a ®xed daily dose of NSAIDs failed to show a difference between sucralfate and placebo17 in the healing of gastric mucosal lesions. IC95 2. IC95 ) 10. The cumulative healing rate after omeprazole 20 mg daily is satisfactory and in line with the data in the literature at 4 and 8 weeks in patients with NSAIDunrelated gastric or duodenal ulcer.5 § N.358 G.1 & 50. probably because of the small number of patients in our study.S.0 & 34.6 in a small subset of patients with gastric ulcer who received continuous treatment with NSAIDs. Endoscopic results and analgesic effects of omeprazole and sucralfate after 4 and 8 weeks of treatment (95% CI for the observed differences in percentage healing between treatment) 4 weeks of treatment Omeprazole 8 weeks of treatment Sucralfate Omeprazole Sucralfate Total healed ulcers 37/45 (82%) 22/43 (51%) (P ˆ 0.3 & 59. Our results show that omeprazole is signi®cantly more effective than sucralfate in inducing the healing of gastric ulcers.007.. Where DU patients are concerned. Table 3. Our data disagree with previous observations20 concerning the not well de®ned role of omeprazole in the prevention of NSAID-induced gastric lesions. IC95 2. CI95 ) 12.S.0 + 57. Aliment Pharmacol Ther 12. IC95 ) 6.

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