Chronic Non-steroidal Anti-inflammatory Drugs Users Research Articles

Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study

Background: The role of Helicobacter pylori infection and especially of the cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial. Methods: A case-control study was carried out including 191 consecutive chronic NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without signs of bleeding of similar age and gender to cases. Multivariate regression analysis was performed for further evaluation of the relationship between H. pylori, CagA status and other risk factors. Results:H. pylori infection was present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR) = 1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly more frequent in cases than in controls (65/106 versus 41/99 P = 0.008). Current smoking (OR = 2.65; 95% CI, 1.14-6.15; P = 0.02), CagA status (OR = 2.28; 95% CI, 1.24-4.19; P = 0.008), dyspepsia (OR = 6.89; 95% CI, 1.84-25.76; P = 0.004) and past history of peptic ulcer disease (OR = 3.15; 95% CI, 1.43-6.92; P = 0.004) were associated significantly with increased risk of bleeding peptic ulcer. Conclusions: The results suggest that CagA-positive H. pylori infection is associated with a more than 2-fold increased risk of bleeding peptic ulcer among chronic NSAIDs users.

The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs.

Although the administration of gastroprotective drugs may reduce the risk of gastrointestinal (GI) bleeding due to intake of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin during chronic treatment, no consensus exists as to whether such co-therapy is effective in short-term prevention, particularly in old age. The aim of our study was to evaluate the risk of bleeding associated with acute and chronic NSAID or aspirin therapy in elderly subjects, and the influence of gastroprotective treatment on such a risk. The study included 467 elderly NSAID or aspirin users and 1784 non-users, who consecutively underwent upper GI endoscopy. The use of NSAIDs and/or aspirin as well as gastroprotective drugs (misoprostol, H2-blockers, proton pump inhibitors) was evaluated during a structured interview. Upper GI tract bleeding was diagnosed on the basis of symptoms and endoscopic signs of recent hemorrhage. 54.2% of patients were acute and 45.8% chronic users of NSAIDs or aspirin. The risk of bleeding was higher in acute [odds ratio (OR) 4.14, 95% CI 2.97-5.78] than chronic users (OR 1.71, 95% CI 1.1-2.67). The risk of bleeding, adjusted for age, gender, Helicobacter (H) pylori infection, and gastroprotective drug use were 7.87 (CI 4.90-12.60) in acute users and 3.97 (95% CI 2.27-6.96) in chronic users of NSAIDs and/or aspirin. The risk of bleeding was significantly associated with acute but not chronic use of regular-dose aspirin (OR 5.53, 95% CI 2.29-13.3), diclofenac (OR 4.44, 95% CI 2.21-8.93), ketorolac (OR 4.81, 95% CI 2.13-10.9), naproxen (OR 14.9, 95% CI 4.23-52.4) or nimesulide (OR 4.06, 95% CI 1.2-13.8). Piroxicam increased the risk of bleeding in both acute (OR 5.36, 95% CI 1.94-14.8) and chronic therapy (OR 5.53, 95% CI 1.23-24.9). In acute users, concomitant therapy with proton pump inhibitors reduced the risk of bleeding compared with non-users (OR 1.05, 95% CI 0.19-5.65), whereas co-treatment with H2-blockers was associated with a significantly higher risk of bleeding than in non-users (OR 3.40, 95% CI 1.28-9.02). Chronic users of NSAIDs or aspirin co-treated with proton pump inhibitors had a lower risk of bleeding (OR 1.12, 95% CI 0.21-6.07) than those treated with misoprostol (OR 1.91, 95% CI 0.33-10.9) or H2 blockers (OR 2.26, 95% CI 0.81-6.36). The risk of upper GI bleeding is significantly higher in elderly acute vs chronic users of NSAIDs or regular-dose aspirin. In acute NSAID or aspirin users, co-treatment with proton pump inhibitors, but not with H2-blockers, may reduce the risk of bleeding compared with non-users.

Impact of NSAIDs prior authorization policy on patients' QoL.

In 1996, the West Virginia Medicaid program targeted nonsteroidal antiinflammatory drugs (NSAIDs) for prior authorization (PA) to ensure cost-effective and appropriate utilization. PA guidelines required that patients must have tried and failed treatment with 2 different classes of generic NSAIDs before a brand-name NSAID could be approved. To evaluate the impact of the requirement of PA for branded NSAIDs on the health-related quality of life (HRQoL) of patients who are chronic users of NSAIDs. Pre- and postintervention quasiexperimental design was used for this study. The sample consisted of continuously eligible Medicaid recipients who were <65 years old and who were diagnosed with rheumatoid arthritis, osteoarthritis, spondylitis, or chronic pain syndromes. Data were collected through a mail survey using the abbreviated version of the Arthritis Impact Measurement Scales. A total of 181 (37.1%) completed surveys were received, 110 (39.2%) from the branded-NSAID user group and 71 (32.7%) from the generic-NSAID user group. Patients who were restricted to generic NSAIDs did not report deterioration in any of the HRQoL domains measured, including mobility, walking and bending, hand and finger function, self care, household activities, social activities, and tension. The requirement of PA for the use of branded NSAIDs did not compromise patients' HRQoL at 8 weeks follow-up.

Management of gastroduodenal ulcers and gastrointestinal symptoms associated with nonsteroidal anti-inflammatory drug therapy: A summary of four comparative trials with omeprazole, ranitidine, misoprostol, and placebo

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of systemic diseases such as rheumatoid arthritis but are associated with a range of adverse gastrointestinal (GI) side effects, including dyspepsia, peptic ulcer, and ulcer complications. Several studies have compared the relative efficacy and tolerability of omeprazole, ranitidine, and misoprostol in the management of NSAID-associated GI adverse events. Objective: The purpose of this paper is to summarize and evaluate the results of 4 clinical studies that compared the efficacy and tolerability of omeprazole, misoprostol, and ranitidine in the acute and maintenance treatment of NSAID-associated gastroduodenal ulcers and GI symptoms. Methods: The 4 trials, which included 1822 patients being treated continuously with NSAIDs, studied omeprazole (20 and 40 mg once daily) as acute treatment for healing gastroduodenal ulcers and erosions and as prophylaxis (20 mg once daily) over 3 to 6 months. Comparators were misoprostol 200 μg 4 times daily or ranitidine 150 mg twice daily in the acute phases and misoprostol 200 μg twice daily, ranitidine 150 mg twice daily, or placebo in the prophylactic phases. Results: Gastric and duodenal ulcer healing rates were higher with omeprazole than with either misoprostol ( P = 0.004 for gastric ulcers; P < 0.001 for duodenal ulcers) or ranitidine ( P < 0.001 for gastric ulcers; P = 0.032 for duodenal ulcers). A significantly larger percentage of patients taking misoprostol had the number of gastric or duodenal erosions reduced from >10 to <5 compared with patients taking omeprazole ( P < 0.001), whereas a significantly larger percentage of patients taking omeprazole achieved the same reduction in number of erosions compared with patients taking ranitidine ( P = 0.008). More patients taking omeprazole remained in remission than patients taking misprostol ( P = 0.001), ranitidine ( P = 0.004), or placebo ( P < 0.001). More patients taking misoprostol (16.9%) or ranitidine (14.1%) discontinued treatment because of adverse events, lack of efficacy, or other reasons compared with patients taking omeprazole (9.9% and 10.2% in 2 studies). Conclusions: Omeprazole was more effective in healing and prophylaxis of NSAID-associated gastroduodenal ulceration and symptoms than misoprostol and ranitidine in chronic NSAID users, and was better tolerated than misoprostol.

Use of nonsteroidal anti-inflammatory drugs and gastroprotective agents before the advent of cyclooxygenase-2—selective inhibitors: analysis of a large United States claims database

Background: Previous studies have shown that 20% to 40% of patients requiring nonsteroidal anti-inflammatory drugs (NSAIDs) are concomitantly prescribed gastroprotective agents (GPAs) such as proton pump inhibitors (PPIs) and H 2-receptor antagonists. Objective: The purpose of this study was to examine NSAID prescription patterns and the concurrent use of GPAs in a large national sample of patients who were prescribed NSAIDs for the first time. Methods: Patterns of NSAID use, particularly chronic NSAID use, and of concomitant use of GPAs were examined using a large US-based prescription database. Patients with at least 1 NSAID prescription dispensed between May 1 and August 31, 1998, were identified. Persons with any NSAID prescription within 4 months prior to the first (index) prescription were excluded. The remaining patients were defined as new NSAID users and then classified as chronic users (≥30 days of supply of NSAIDs during the 120 days of follow-up after the first NSAID prescription) or acute users (<30 days of NSAID supply during the 120 days of follow-up). Concomitant GPA use was defined as receipt of any GPA prescription between the fill date of NSAID prescription and 125% of days of supply. NSAIDs included diclofenac/misoprostol (in a fixed combination), diclofenac, naproxen, nabumetone, ibuprofen, and “other” (comprising several less frequently prescribed agents). Patients were classified as users of a particular NSAID based on the first NSAID prescription they received. GPAs included PPIs, H 2-receptor antagonists, and misoprostol. Results: A total of 3,028,808 new NSAID users were identified. Chronic NSAID users (47.8% of the sample) were older than acute users. The percentage of new chronic users aged ≥65 years for each of the NSAIDs was 41.2% for diclofenac/misoprostol, 33.0% for nabumetone, 30.8% for diclofenac, 20.4% for naproxen, and 20.3% for ibuprofen. The percentage of women was higher among patients treated with diclofenac/misoprostol than among patients treated with all other NSAIDs ( P < 0.001). During the 120 days of follow-up, the percentages of NSAID users with concomitant GPA use were 22.7% for diclofenac/misoprostol, 16.3% for diclofenac, 11.5% for naproxen, 18.0% for nabumetone, 12.3% for ibuprofen, and 14.8% for other NSAIDs. Based on days of supply, the rates of concomitant GPA use were 31.1%, 23.6%, 17.6%, 27.3%, 18.8%, and 22.5% for diclofenac/misoprostol, diclofenac, naproxen, nabumetone, ibuprofen, and other NSAID users, respectively. Among those who were taking GPAs before the NSAID index prescription date, ∼89% continued GPA therapy. Conclusions: Approximately 22% of the days of NSAID supply were covered by GPAs. Prior GPA use was the strongest predictor of subsequent concomitant GPA/NSAID use. Differences in GPA use were observed among patients using different NSAIDs.

Helicobacter pylori infection and the use of NSAIDs

Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs) can each result in gastroduodenal ulcers and ulcer complications. Recent studies have suggested that there is an interaction between the two causes such that elimination of H. pylori before NSAID treatment decreases the occurrence of ulcers. This led to the conclusion of the Maastricht 2000 meeting that H. pylori eradication should be considered before embarking on long-term NSAID therapy. One of the main sources of confusion is related to the fact that prospective endoscopic studies testing various drugs for prevention of NSAID ulcers among chronic NSAID users are probably not directly applicable to problems of clinical ulcers and of ulcer complications. It has become clear that, to be interpretable clinically, such studies must provide separate analyses based on H. pylori status, history of ulcer, or an ulcer complication. Overall, the data strongly support the notion that eradication therapy is beneficial for primary prophylaxis. In contrast, one would expect little benefit when NSAIDs caused the clinical ulcer (secondary prevention) and, at best, H. pylori eradication has a modest effect on the prevention of recurrent ulcer bleeding in NSAID users who have suffered ulcer complications. The data support the notion that H. pylori eradication therapy should be given to all H. pylori -infected patients with peptic ulcers irrespective of whether or not they have used NSAIDs. Proton pump inhibitors are superior to placebo for the prevention of ulcer recurrence but are inferior to full-dose misoprostol for the prevention of ulcers among those with NSAID ulcers and no H. pylori infection. Selective COX-2 inhibitors appear to reduce markedly, but not eliminate, ulcer complications among chronic NSAID users.

Helicobacter pylori and NSAID gastropathy: an ambiguous association.

Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with adverse gastro- intestinal effects ranging from mild dyspepsia to serious complications such as bleeding peptic ulcer. However, controversy persists regarding the interaction between these two well-documented risk factors. Physiology studies reveal that H. pylori infection can protect the upper gastrointestinal tract by increasing prostaglandin levels. In contrast, clinical trial evidence suggests that eradication of H. pylori infection leads to a decreased risk for endoscopic ulcers in people taking NSAIDs. Given the rates of morbidity and mortality and costs attributable to NSAID-associated toxicity, preventive strategies to reduce NSAID side-effects remain important. Until controlled investigations definitively quantify the effect of H. pylori infection and eradication on clinically significant adverse events, a compelling argument can be made for H. pylori testing of chronic NSAID users at increased risk for ulcer disease and eradicating the organism if present.

Helicobacter pylori and nonsteroidal anti-inflammatory drugs: interaction with proton pump inhibitor therapy for prevention of nonsteroidal anti-inflammatory drug ulcers and ulcer complications—future research needs

Two recently reported studies of nonsteroidal anti-inflammatory drugs (NSAIDs), the Omeprazole versus Misoprostol for NSAID-induced Ulcer Management and the Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment studies, concluded that omeprazole was superior to a subtherapeutic misoprostol or an ineffective dose of ranitidine for the endpoint, prevention of gastroduodenal ulcers in chronic NSAID users. Helicobacter pyloristatus was collected prospectively but was not reported. We report separate analyses for patients with unequivocal NSAID ulcers ( H. pylori negative) and patients whose NSAID use was complicated by the presence of an active H. pylori infection. Omeprazole was superior to placebo for the prevention of ulcer recurrence in chronic NSAID users. However, omeprazole was not significantly better than a subtherapeutic dose of misoprostol for the prevention of gastroduodenal ulcers in chronic NSAID users. Misoprostol was superior to omeprazole for the prevention of gastric ulcers among those patients with unequivocal NSAID ulcers (8.2% vs 16.6%, respectively; P <0.05). Omeprazole was not statistically different from misoprostol for gastric ulcer prevention in those whose NSAID use was complicated by an active H. pylori infection. Ranitidine and omeprazole were also not statistically different for the prevention of unequivocal NSAID gastric ulcers (14.6% vs 11.6%, respectively; P = 0.56). That the Misoprostol Ulcer Complications Outcomes Safety Assessment (MUCOSA) trial found full-dose misoprostol to be more effective in ulcer prevention than it was in prevention of ulcer complications suggests that either many of the ulcer complications were related to H. pylori ulcers or that more antisecretory activity than can be provided with misoprostol is needed, or both. The question remains whether the combination of low-dose misoprostol plus an antisecretory drug (either an H 2-receptor antagonist or a proton pump inhibitor) would provide superior results compared with either alone. That omeprazole was not superior to one half the dose of misoprostol used in the ulcer complication prevention, or MUCOSA, study indicates that it would not be prudent to suggest that ulcer prevention with omeprazole alone would be able to provide similar protection to misoprostol.

Who needs prophylaxis of nonsteroidal anti-inflammatory drug-induced ulcers and what is optimal prophylaxis?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used successfully by many patients for the treatment of the signs and symptoms of arthritis, and other painful and inflammatory disorders. However, traditional nonselective NSAIDs that inhibit COX-1 and COX-2 lead to a state of propensity for gastric and duodenal ulcer disease and ulcer complications. The point prevalence of endoscopic ulcers ranges from 14 to 44% of patients using NSAIDs. Moreover, it is estimated that 1.46-1.90% of chronic NSAID users develop serious upper gastrointestinal (UGI) toxicity annually, most notably UGI bleeding, gastric/duodenal obstruction or ulcer perforation. In the USA, it has been estimated that 107,000 hospitalisations and 16,500 deaths occur annually related to the use of nonselective NSAIDs. Because these ulcer complications are often not heralded by chronic symptoms of dyspepsia, symptoms alone are not sufficient to guide long-term management of NSAID-related toxicity. Instead, prophylactic and preventive therapies are recommended in patients at above-average and high risk. Epidemiological data have identified that patients with a past history of ulcer disease, past history of UGI bleeding, greater age, concomitant corticosteroid use, and those who use higher doses and multiple NSAIDs fall into this category. Other risk factors of lesser importance have also been identified. A controversial issue remains regarding the possible increased risk of NSAID-associated ulcers and ulcer complications in patients who are infected with Helicobacter pylori. Prophylactic therapies have been evaluated primarily in randomised clinical trials, with the rate of endoscopic ulcers as the primary endpoint. It is assumed, but not proven, that these endoscopic ulcer rates are surrogate markers for gastrointestinal toxicity and are predictive of the rate of significant UGI adverse events. In the only outcomes trial to date, it was reported that misoprostol (200 microg 4 times daily) caused an approximately 50% reduction in serious UGI adverse events in a large 6-month trial involving rheumatoid arthritis patients. In parallel, this approximates the 50% reduction of endoscopic ulcers seen in randomised controlled trials using misoprostol. While H2 receptor antagonists are ineffective agents at traditional doses, proton pump inhibitors have been clearly shown to reduce the rate of endoscopic ulcers in several trials. In fact, the efficacy approximates to the efficacy seen with misoprostol. Beyond efficacy and in practical terms, the choice of optimal prophylaxis should take into consideration patient compliance, patient satisfaction, side-effects and cost.

Protective effect of chronic NSAID use on cognitive decline in older persons.

To verify whether chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a protective effect against cognitive decline in older persons. Prospective study with a 3-year observation period. Three communities of the Established Populations for Epidemiologic Studies of the Elderly (EPESE). A population-based sample of 7671 subjects who received an in-person interview at the sixth annual follow-up. Persons with documented NSAID use at the time of the interview and 3 years before were considered chronic users (21%), while all other persons were considered as nonusers. Change over time in cognitive function assessed as the number of correct answers to a 9-item version of the Short Portable Mental Status Questionnaire (SPMSQ). For every level of SPMSQ score measured at the beginning of the observation period, the mean SPMSQ score after 3 years was higher in chronic NSAID users than in nonusers. Cognitive function at the end of the observation period was significantly higher in chronic NSAID users than in controls, adjusting for initial SPMSQ score and potential confounders. Older age, female gender, education, and history of cerebrovascular disease were also independent predictors of lower SPMSQ score. In the multivariate analysis, the magnitude of the protective effect estimated for NSAID use was comparable to a difference in age of 3.5 years. The percentage of persons who started above a specific SPMSQ score cut-point and deteriorated below that cut-point over a 3-year period was significantly lower in chronic NSAID users than in nonusers (30.2% vs 34.3%, P = .03, for decline below SPMSQ score of 8 and 12.3% vs 14.4% for decline below SPMSQ score of 6, P = .04). After controlling for potential confounders, the relative risk of cognitive declining in chronic NSAID users compared with nonusers was 0.82 (95% Confidence Interval: 0.69-0.98) for a decline below a score of 8, and 0.80 (95% CI: 0.66-0.98) for a decline below a score of 6. These results support the association between NSAID use and reduction in cognitive decline in older persons. Ultimately, randomized controlled trials must be done to prove a beneficial effect definitively.

Association of chronic non-steroidal anti-inflammatory drugs use and cognitive decline in non-demented elderly patients admitted to a geriatric evaluation and rehabilitation unit.

In a geriatric evaluation and rehabilitation unit (GERU), 258 elderly patients (M: 71, F: 187; mean age 77.4 +/- 7.5) scoring 22 or more at Mini-Mental State Examination (MMSE) consecutively admitted were assessed in order to evaluate the effects of non-steroidal anti-inflammatory drugs (NSAID) chronic treatment on cognitive status in non-demented elderly patients. Sixty-six patients (25.6%) were considered chronic NSAID users. Patients chronically assuming NSAADs showed a significantly higher MMSE score than non-users (26.9+/-2.1 vs 25.7+/-2.5, P<0.0005 ). After controlling for potential confounders in a multivariate model, chronic NSAID use remained independently associated with MMSE score. The results support a positive association between chronic NSAID use and cognitive function in non-demented elderly patients. Randomized controlled trials will be needed to definitively prove this beneficial effect.

Historical overview of non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are efficacious in the control of arthritis symptoms and have become the mainstay of arthritis therapy. While NSAIDs' chief mechanism of action has long been assumed to be the inhibition of prostaglandin synthesis, further investigation has implicated additional mechanisms, and shed light upon additional side-effects. Adverse renal effects and effects on bone and cartilage metabolism are counted among worrisome NSAID-induced side-effects, but gastrointestinal side-effects represent the greatest threat to chronic NSAID users. It is important that we combine documented experience of side-effect risk with our growing knowledge of potential risk to frame a prescriptive approach to the arthritis patient that encompasses symptom management as well as patient protection.

Gastric adaptation to nonsteroidal anti-inflammatory drugs in man.

Adaptation describes the phenomenon in which visible gastric mucosal injury lessens or resolves completely despite continued administration of an injurious substance such as aspirin. Adaptation occurs in man although the mechanism remains unclear. Recent evidence suggests increased cell proliferation and correction of nonsteroidal anti-inflammatory drug induced reduction in gastric blood flow as possibly being important. Gastric erosions and ulcers in chronic nonsteroidal anti-inflammatory drug users represent failed adaptation. Gastric erosions and ulcers in chronic nonsteroidal anti-inflammatory drug users represent failed adaptation. The factors responsible for failure of adaptation are unknown but one clue is that there appears to be a dose-response effect relating anti-inflammatory dose and effectiveness of adaptation (i.e., adaptation is delayed, or less effective, when higher anti-inflammatory doses are administered). Gastric adaptation can be enhanced by co-therapy with synthetic prostaglandins but not with sucralfate or H2-receptor antagonists.

Prevention of NSAID-induced Gastric Ulcer

Letters1 December 1991Prevention of NSAID-induced Gastric UlcerRonald L. Koretz, MDRonald L. Koretz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-11-911 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: Agrawal and coworkers (1) described a prospective, randomized controlled trial comparing sucralfate and misoprostol in the treatment of patients with nonulcer pain associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). They observed that patients treated with misoprostol had a five- to ten-fold decrease in the incidence of subsequent gastric ulceration. The implication is that misoprostol is the preferred agent.The development of a gastric ulcer was the primary end point of the study. The occurrence of any serious complications (for example, hemorrhage or perforation) of ulcer disease was not reported. Other observations indicated a greater percentage...Reference1. AgrawalRothGrahamWhiteGermainBrown NSDRBJ. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized controlled trial. Ann Intern Med. 1991;115:195-200. LinkGoogle Scholar1. AgrawalRothGrahamWhiteGermainBrown NSDRBJ. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized controlled trial. Ann Intern Med. 1991;115:195-200. LinkGoogle Scholar2. Soll A. Pathogenesis of peptic ulcer and implications for therapy. N Engl J Med. 1990;322:913-4. Google Scholar3. SollKvrataMcGuigan AJJ. Ulcers, nonsteroidal anti-inflammatory drugs and related matters. Gastroenterology. 1989;96:568. CrossrefGoogle Scholar1. AgrawalRothGrahamWhiteGermainBrown NSDRBJ. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized controlled trial. Ann Intern Med. 1991;115:195-200. LinkGoogle Scholar2. Soll A. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med. 1991;114:307-19. LinkGoogle Scholar3. LanzaRoyerNelson FGR. Endoscopic evaluation of the effects of aspirin, buffered aspirin, and enteric-coated aspirin on gastric and duodenal mucosa. N Engl J Med. 1980;303:136-8. CrossrefMedlineGoogle Scholar4. SilvosoIveyButtLockardHoltSisk GKJOSC. Incidence of gastric lesions in patients with rheumatic disease on chronic aspirin therapy. Ann Intern Med. 1979;91:517-20. LinkGoogle Scholar5. BrooksDay PR. Nonsteroidal anti-inflammatory drugs-differences and similarities. N Engl J Med. 1991;324:1716-25. CrossrefMedlineGoogle Scholar1. AgrawalRothGrahamWhiteGermainBrown NSDRBJ. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized controlled trial. Annals Intern Med. 1991;115:195-200. LinkGoogle Scholar2. AgrawalPatelMahatmaDajani NRME. Nonsteroidal antiinflammatory drugs and acute upper gastrointestinal bleeding: A prospective study. J Am Acad Min Phys. 1991;2:64-6. MedlineGoogle Scholar3. FDC reports. Chevy Chase, Maryland. 30 November 1988. Google Scholar4. GrahamAgrawalRoth DNS. Prevention of NSAID-induced gastric ulcer with the synthetic prostaglandin, misoprostol. A multicenter, double-blind, placebo-controlled trial. Lancet. 1988;2:1277-80. CrossrefMedlineGoogle Scholar5. GrahamStromattJaszewski DSR. Prevention of duodenal ulcer in arthritics who are chronic NSAID users: a multicenter trial of the role of misoprostol. Gastroenterology. 1991;100:A75. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Olive View Medical Center Sylmar, CA 91342 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBeta-Agonists in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease 1 December 1991Volume 115, Issue 11Page: 911-913KeywordsDrugsGastric ulcersHemorrhageNSAIDsPatientsUlcers Issue Published: 1 December 1991 PDF downloadLoading ...