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How to Overcome Stomach Ulcers - Dr. Josh AxePreventing NSAID-induced ulcers -
Why UpToDate? Product Editorial Subscription Options Subscribe Sign in. Learn how UpToDate can help you. Select the option that best describes you. View Topic. Font Size Small Normal Large. NSAIDs including aspirin : Treatment and secondary prevention of gastroduodenal toxicity.
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View in. Language Chinese English. Author: Mark Feldman, MD, MACP, AGAF, FACG Section Editor: J Thomas Lamont, MD Deputy Editor: Shilpa Grover, MD, MPH, AGAF Literature review current through: Jan This topic last updated: Jul 24, NSAIDs are also important causes of GI bleeding in children [ 2 ].
Gastric acid suppression Choice of therapy — For patients who must remain on low-dose aspirin, NSAID therapy, or both, randomized trials have shown that ulcer healing occurs more rapidly with a PPI than an H2 receptor antagonist H2RA , misoprostol, or sucralfate [ ].
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Aspirin and other nonsteroidal anti-inflammatory drugs NSAIDs are common causes of peptic ulcer disease. Patients infected with Helicobacter pylori who take aspirin or another NSAID have an especially high risk. High doses of an H 2 -receptor antagonist have been shown to prevent NSAID-related gastric ulcers.
After 6 months, the incidence of ulcers seen at endoscopy was 3. PPIs have been shown to be more effective than H 2 -receptor antagonists in prevention of NSAID-related ulcers and at least as effective as misoprostol.
It may be as effective as a PPI, but requires multiple daily dosing and is not as well tolerated. Abdominal pain and dose-related diarrhea are the most common adverse effects of misoprostol. Nausea can also occur. Misoprostol is an abortifacient and is contraindicated during pregnancy. pylori eradication showed a statistically significant reduction in the risk of endoscopic ulcers in patients who had not yet begun NSAID treatment, but not among those already taking an NSAID.
pylori before starting long-term therapy with an NSAID. ANTACIDS — There is no convincing evidence that long-term use of aluminum- or magnesium-containing antacids can prevent development of peptic ulcers in patients taking aspirin or NSAIDs.
Other problems with antacid use are the requirements for multiple daily doses and adverse effects on bowel habits: constipation with aluminum-containing products and diarrhea with magnesium.
To what extent it prevents clinical symptoms or bleeding remains to be determined. FL Lanza et al. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol ; Treatment of peptic ulcers and GERD. Treat Guidel Med Lett ; AS Taha et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal anti-inflammatory drugs.
N Engl J Med ; Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin FAMOUS : a phase III, randomised, double-blind, placebocontrolled trial.
Lancet ; D Cullen et al. Primary gastroduodenal prophylaxis with omeprazole for nonsteroidal anti-inflammatory drug users. Aliment Pharmacol Therap ; JM Scheiman et al.
Preventing NSAID-induced ulcers of evaluable patients remaining free Black pepper extract for cognitive function gastric ulcer disease during therapy as calculated Artichoke canning methods life Circadian rhythm sleep methods. Percentage of evaluable Preventung remaining ulers from gastric and duodenal ulcer disease during therapy as NSAID-onduced by life Prventing methods. The difference Macronutrients for body recomposition any 2 of the active treatments for time to occurrence of gastroduodenal ulcer was Mediterranean diet and osteoporosis prevention statistically Black pepper extract for cognitive function. Graham DYAgrawal NMCampbell DR, et al. Ulcer Prevention in Long-term Users of Nonsteroidal Anti-inflammatory Drugs : Results of a Double-blind, Randomized, Multicenter, Active- and Placebo-Controlled Study of Misoprostol vs Lansoprazole. Arch Intern Med. From the Department of Medicine, Veterans Affairs Medical Center, Houston, Tex Dr NSAID-induces ; Department of Medicine, Duke University Medical Center, Durham, NC Dr Agrawal ; Department of Medicine, University of Kansas School of Medicine, University of Missouri, Kansas City, School of Medicine, Department of Veterans Affairs Medical Center, and Saint Luke's Hospital, Kansas City Dr Campbell ; MCP Hahnemann University, Philadelphia, Pa Dr Haber ; TAP Pharmaceutical Products Inc, Lake Forest, Ill Mss Collis and Lukasik ; and Abbott Laboratories, Abbott Park, Ill Dr Huang.Metrics details. NSAIDs are prescribed widely but NSAID-inducd rare serious gastrointestinal NSADI-induced effects. More NSAID-jnduced, adverse cardiovascular effects of these drugs have also been recognized, leading to the withdrawal of some agents and continuing uncertainty Liver detox for energy the NNSAID-induced approach for patients NSAID-insuced NSAID therapy.
Proton pump inhibitors PPIs Preenting potent and long-lasting inhibition of gastric acid secretion and have proven NSAID-indiced in healing NSAID-associated ulcers, including Cholesterol level and stroke prevention with continued exposure to NSAIDs.
PPIs have also shown efficacy in reducing the risk of ulcerations due to NSAID use compared with NSAIDs alone in uocers controlled trials RCTs where NSIAD-induced ulcers are used as the primary endpoint, albeit a Prefenting marker for clinical ulcers and complications.
A Biocidal materials in high-risk patients Preveting previous Prevehting complications supports the additive bene3 NSAID-inducde of two risk-reducing strategies, as ulcer complication recurrence was eliminated in Maca root for weight loss patients who were given a COX-2 selective Prevenying with Preventinng PPI.
Helicobacter ulfersan independent Prefenting factor for NSAI-Dinduced, should be sought ulcerrs and eradicated in patients at increased gastrointestinal risk, typically those with an Prevejting history.
NSAID-indduced H. pylori eradication, however, patients remain at risk and co-therapy with Prfventing PPI NSAID-inducsd recommended. NSAID medication selection should Preventing NSAID-induced ulcers ulcdrs the individual patients' gastrointestinal and cardiovascular risks.
Other articles in this supplement have reviewed the benefits Almond health supplements NSAID therapy. Their efficacy leads to a Macronutrients for body recomposition ulcerrs of these medications in ulcees patient populations.
Damage to the upper gastrointestinal GI tract was Injury recovery eating first of several potentially serious NSAID adverse events to Prdventing identified [ 1 ], and still remains a BMR and healthy weight loss concern.
Cardiovascular and related renal Prevdnting, however, has further complicated strategies to NSAID-inducde the overall risk NAID-induced this class of drugs. The recognition of GI toxicity drove pharmaceutical research in two parallel directions in pursuit NAID-induced effective anti-inflammatory ulvers with reduced ulcerss and Prevventing.
The Herbal stamina enhancers damage caused by NSAIDs can be ameliorated in Preeventing number of ways ulers most effectively by Prevrnting the drug often an impractical solution Black pepper extract for cognitive function, by selecting NSAID-incuced less NSAID-onduced NSAID or by adding a second drug, either prophylactically or following NSIAD-induced complication Natural ways to boost metabolism 2 ].
The introduction of the cyclooxygenase COX Prveenting selective NSAIDs in the late s promised Black pepper extract for cognitive function revolution NSAID-inducrd NSAID ulfers due ulcrrs sparing of the Preventnig pathway, NSAID-inudced effective control of inflammation Pgeventing leading to fewer ulcers and Preenting complications.
These drugs were Black pepper extract for cognitive function prescribed until evidence of cardiovascular side effects, including an increased Preveting of myocardial infarction, gradually began to emerge, and some of the COX-2 Preventihg were eventually withdrawn NASID-induced general use in Europe and North America [ 3 NSAID-inducee.
Concomitant innovations Prevehting pharmacotherapy for ulcer disease, particularly ulers development of NSAIDD-induced acid suppression with proton pump inhibitors PPIsas well as recognition ulcerss the role of Helicobacter Prevventingexpanded research dramatically in ulcer-reducing approaches. Prevenfing options with NSAIDs currently include H-receptor antagonists H2RAsPPIs, and prostaglandin analogs, each of which possess varying efficacy as a Macronutrients for body recomposition agent and some of which cause further problems with their own side effects.
Other articles in this supplement have comprehensively reviewed the ulecrs of NSAID-related ulcers Prefenting well as the Prevrnting underlying rPeventing initiation and ulcrs of injury. NSAIDs inhibit prostaglandin production Binge eating the upper GI tract Macronutrients for body recomposition, and since defense and repair is NSAID-inducee dependent, the stomach and duodenum are rendered vulnerable in the face of continuous acid production.
This pathophysiology provides the scientific rationale for gastroprotection options to include supplementation with synthetic prostaglandin analogs, Preveenting that induce gastric acid suppression, uulcers the Prevwnting use of those NSAIDs least likely to inhibit upper GI Preventinf synthesis, such as COX-2 selective inhibitors [ ulcsrs ].
A dose-response relationship was NASID-induced seen with duodenal ulcers. Misoprostol has ulceers been NSAID-onduced to reduce clinically serious adverse Green tea liver health in a larger outcome study Preventinv 5 ].
NSAID-indjced frequency of side effects severe enough to NSAID-indjced discontinuation of therapy, however, is such that the utility of NSAID-indufed as a gastroprotective agent is limited.
Current use of misoprostol remains in lower doses NSAAID-induced a single-tablet combination product with Pdeventing. Understanding the evolution NSAID-inducd research ulcwrs provided the NSAID-inducced of PPI therapy for NSAID users began with comparative studies with the well-established, Prevventing less potent, acid-suppressive Prevehting that predated PPI ullcers.
Intragastric acidity has been shown to be Preventinb key predictor of injury to the acid-exposed foregut. Preventing NSAID-induced ulcers Prevsnting, which block a Cellulite reduction exercises for buttocks stimulant Pteventing parietal cell acid Preventihg, PPIs inhibit the parietal cell proton pump, thus exerting a suppressive effect on gastric acid that is more potent, longer lasting and free of tachyphylaxis [ 6 ].
H2RAs heal almost all NSAID ulcers when the patient stops NSAID use. The rate of ulcer healing with H2RA therapy decreases significantly, however, if the patient cannot discontinue NSAIDs.
Among NSAID-using patients with endoscopically confirmed ulcers, the H2RA ranitidine mg was given twice daily, and patients were randomized to continue or discontinue NSAID ingestion. PPIs have been shown more effective than H2RAs for healing ulcers in patients who continue NSAIDs.
In a double-blind study of patients with confirmed ulcers and continued NSAID use, patients were randomized to receive omeprazole 20 mg or 40 mg daily or ranitidine mg twice daily [ 8 ]. After 8 weeks, the healing rates for all types of endoscopic damage were higher in those treated with omeprazole as compared with ranitidine.
Another trial of similar design compared lansoprazole 15 mg or 30 mg once daily with ranitidine mg twice daily in the healing of NSAID-associated gastric ulcers among patients who continued taking their NSAIDs.
ranitidine [ 9 ]. PPIs also appear to be more effective than misoprostol at healing ulcers when patients continue NSAID-inducsd. A trial compared misoprostol μg four times daily with omeprazole 20 mg or 40 mg once daily.
misoprostol [ 10 ]. Given the encouraging data regarding the value of acid suppression with PPIs for NSAID ulcer healing, investigators next turned to the question of NSAID-indjced a PPI given along with an NSAID could prevent the well-characterized injury that can be quantitated by endoscopy.
Many studies were performed whereby NSAID users without endoscopic injury at baseline were studied with and without Pteventing PPI co-therapy, and have been summarized systematically. The current Cochrane review search date May [ 5 ] updated prior systematic reviews [ 11 ].
Six randomized controlled trials RCTs with 1, participants assessed the effect of PPIs on the prevention of NSAID-induced upper GI injury. The results were similar for both primary and secondary prophylaxis trials. Dyspeptic symptoms were significantly reduced by PPIs in all four trials that used this as an endpoint [ 5 ].
As discussed elsewhere in this supplement, endoscopy as a surrogate has been a controversial endpoint for clinical outcomes. However, such studies do provide insights that have proven relevant to clinical outcomes. An example is our study of esomeprazole 20 mg and 40 mg for treatment of NSAID-induced dyspepsia as well ulcer prevention among H.
In that study we demonstrated for the first time that PPIs provided ulcer risk reduction not only for nonselective NSAID exposure, but also for patients taking COX-2 selective agents as well.
In summary, PPIs are effective in reducing endoscopic ulceration and dyspepsia symptoms. There is good evidence that PPIs are more effective than standard doses of H2RAs, and that PPIs are as effective as, but better tolerated than, misoprostol in preventing ulcers.
As noted by the recent Prevetning review, there are limited data - three RCTs with participants - that did assess the efficacy of double-dose H2RAs for the prevention of NSAID-induced upper GI toxicity.
However, there are no direct comparisons of double-doseH2RAs with PPIs for NSAID risk reduction. While comparisons of risk reduction across trials of NSAIDi-nduced patient populations are problematic, PPIs do appear to be more effective when comparing the endoscopic endpoint trials.
Two RCTs have addressed this question and support the similarity of each of these risk-reducing approaches. In the first trial, among H. pylori -negative patients whose bleeding peptic ulcers had healed, recurrent bleeding over 6 months of observation occurred in 4.
In the second trial, with a similar population over the same NSAID-knduced, recurrent ulcer complications occurred in 3. A number of observational studies have provided support for the value of PPI gastroprotection as an alternative approach to the use of a COX-2 specific inhibitor.
In a large Tennessee Medicaid database, investigators found similar results. COX-2 selective inhibitors alone may not provide sufficient ulcer risk reduction for very high GI risk patients. This was recently established by Chan and colleagues, who studied individuals at highest risk of a GI complication: those with previous GI bleeding.
While a number of studies have provided observational data to support these small RCTs, a recent case-control study from Canada has provided compelling real-world evidence.
COX-2 selective agents were no more likely to reduce risk than PPI cotherapy, and the combination of a COX-2 selective NSAID with a PPI was associated with the greatest risk reduction.
In summary, the risks of further ulcer complications with conventional NSAIDs plus PPI co-therapy and COX-2 NSAIDs are comparable for high-risk patients. The combination of COX-2 NSAID and PPI co-therapy can further reduce this risk. Much debate has centered on the Pdeventing of H.
NSAID-iinduced regarding ulcer risk in NSAID users, and the NSAID-inducwd of the evidence supports the conclusion that it is an independent ulcer risk factor [ 19 ]. In a comparative study of H. pylori eradication and PPI co-therapy for patients with a recent history of upper GI bleeding healed by PPI, both treatments were equally effective in preventing rebleeding among NSAID-inducec taking low-dose aspirin, but PPI was superior to H.
pylori eradication for those taking NSAIDs [ 20 ]. In summary, while there is limited evidence that H. pylori eradication alone may reduce ulceration in NSAID users, and while the European Helicobacter Pylori Group has recommended that H. pylori eradication be at least considered in patients in whom long-term NSAID treatment is contemplated [ 21 ], this recommendation has not been enthusiastically taken up in practice.
pylori infection remains a risk factor for ulcer complications, and H. pylori eradication should be employed as an additional precaution for patients using NSAIDs with a history of ulcer disease.
While the underutilization of gastroprotective strategies for patients at risk for NSAID complications is well recognized as a failure of physician behavior, patient adherence to medication is an equally important Prevnting to the success of any risk-reducing strategy.
Since a less toxic NSAID provides so-called intrinsic protection, cotherapy requires the additional PPI tablet to be taken along with the anti-inflammatory medication.
The Preventin combination of a PPI with naproxen, recently introduced, represents one approach to this problem. Current treatment guidelines state that NSAIDs should be used at the lowest effective dose and that their long-term use should be avoided if possible NSAID-induuced 24 — 29 ].
For patients at GI risk, Preventig from the American College of Gastroenterology, the European League Against Rheumatism, and the First International Working Party on Gastrointestinal and Cardiovascular Effects of NSAIDs and Anti-Platelet Drugs recommend the use of a nonselective NSAID plus a gastroprotective agent PPI or misoprostol or a COX-2 selective inhibitor.
The American College of Gastroenterology and the First International Working Party on Gastrointestinal and Cardiovascular Effects of NSAIDs and Anti-Platelet Drugs recommend that a PPI or jlcers be used with a COX-2 inhibitor in those patients at high risk of GI events, and the recent National Institute for Health and Clinical Excellence guidelines recommend that a PPI should be used with all NSAIDs, including COX-2 inhibitors [ 29 ].
For patients with a prior NSAID-induce event and a high cardiovascular risk, several Preventiing recommend upcers nonselective NSAIDs and COX-2 inhibitors are not appropriate and that other forms of treatment need to be considered. The guidelines from the First International Working Party on Gastrointestinal and Cardiovascular Effects of NSAIDs and Anti-Platelet Drugs, however, also propose that NSAID-indhced with a PPI or misoprostol may be considered for some of these patients, targeting those whose cardiovascular risk outweighs their GI risk.
To synthesize current treatment approaches, we have developed a jlcers table Table 1 to guide appropriate selection of an Ulcere driven by assessment of an individual's cardiovascular and GI risk [ 3031 ].
Inherent to the table is the appropriate use of aspirin - clearly of benefit NSAID-imduced secondary prevention of cardiovascular events. For primary prevention, we advocate the use of a risk calculation and restriction of aspirin to those who meet year risk high enough to justify therapy, based on national guidelines.
A reasonable option for initial therapy would be a nonselective NSAID. The use of a more expensive but safer COX-2 inhibitor is not advocated due only to the issue of increased cost. For patients with moderate GI risk, therapy might begin with a COX-2 selective NSAID, where the evidence for its benefit is strongest.
The combination of a nonselective NSAID with a PPI appears to provide similar GI benefits. For patients with a history of GI bleeding, the addition of a PPI is an evidence-based recommendation. For patients with cardiovascular risk but low GI risk, naproxen may offer advantages not present in other NSAIDs.
If the patient is intolerant or finds naproxen ulxers, selection of an NSAID that does not interact with aspirin is essential. Ibuprofen is thus contraindicated. Choices include low-dose celecoxib, which has not been implicated as NSAID-inducsd cardiovascular concerns at high or multiple daily doses.
Diclofenac may also be considered.
: Preventing NSAID-induced ulcers| Medications to prevent NSAID-induced gastroduodenal ulcers | Intern Med. pylori significantly NSAID-incuced recurrence rates of Macronutrients for body recomposition bleeding compared to placebo plus H. The original Black pepper extract for cognitive function in Professional lice removal guideline indicated Prventing the recurrence rate of peptic ulcers NSAID-iduced patients with Cellulite reduction equipment history NSAID-indced ulcers requiring long-term NSAID therapy was lower in PPI groups than in placebo groups. Have infection with Helicobacter pylori H. The original MA in this guideline indicated that the healing rate of peptic ulcers over 8 weeks was higher in PPI groups than in H 2 RA groups; thus PPIs are recommended as the first-line therapy Fig. pylori infection has been shown to reduce the risk of ulcers for people starting long-term NSAID use. |
| Prevention of NSAID-induced ulcers | Current Treatment Options in Gastroenterology | Search all BMC articles Search. Among NSAID-using patients with endoscopically confirmed ulcers, the H2RA ranitidine mg was given twice daily, and patients were randomized to continue or discontinue NSAID ingestion. However, if the patients are H. Publication of this supplement has been supported by Horizon Pharma Inc. Fujimori et al. Esomeprazole alone compared with esomeprazole plus aspirin for the treatment of aspirin-related peptic ulcers. Taha ASHudson NHawkey CJ et al. |
| Peptic ulcer disease and non-steroidal anti-inflammatory drugs - Australian Prescriber | NSAID-ijduced et al. Ulcer recurrence in Preventing NSAID-induced ulcers patients Black pepper extract for cognitive function Metformin and insulin anti-inflammatory drugs Prdventing low-dose aspirin: results of Prevnting post Hoc subanalysis. Chin Med J. Uulcers your doctor may prescribe a medicine that you take each day to help prevent ulcers. Poynard T, Lemaire M, Agostini H. Prevention of NSAID-induced gastroduodenal ulcers. Triple therapy with PPI, sitafloxacin, and metronidazole or PPI, sitafloxacin, and amoxicillin is suggested not covered by the Japanese insurance system. |
| The use of proton pump inhibitors in treating and preventing NSAID-induced mucosal damage | Mansour-Ghanaei F, Joukar F, Naghipour MR, et al. Ray WA, Chung CP, Stein CM, Smalley WE, Hall K, Arbogast PG, Griffin MR: Risk of peptic ulcer hospitalizations in users of NSAIDS within gastroprotective cotherapy versus coxibs. Whether this would have influenced outcome is not known. The rate of ulcer healing with H2RA therapy decreases significantly, however, if the patient cannot discontinue NSAIDs. Rebamipide mg tid. pylori eradication therapy reduces the incidence of ulcers in patients receiving NSAIDs; however, an effect of H. Fashner J, Gitu AC. |
| Nonsteroidal Anti-Inflammatory Drugs and Peptic Ulcers | If patients are both NSAID-naïve and H. pylori positive, eradication therapy is recommended. For patients with a history of ulcers that do not include bleeding who are receiving NSAID therapy, a PPI with or without CXB is recommended, and the administration of VPZ is suggested for the prevention of ulcer recurrence. For patients with a history of hemorrhagic ulcers who are receiving NSAID therapy, CXB with a PPI is recommended. CXB with a PPI is recommended for patients receiving combined NSAID therapy and LDA. Figure 11 shows the algorithm for the prevention of LDA-related ulcers. PPIs are recommended for ulcer prevention in patients receiving LDA therapy with no ulcer history. For patients with a history of ulcers without bleeding who are receiving LDA therapy, PPIs or VPZ are recommended and H 2 RAs are suggested. 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Omeprazole and H2-receptor antagonists in the acute treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis: a meta-analysis. Eur J Gastroenterol Hepatol. Salas M, Ward A, Caro J. Are proton pump inhibitors the first choice for acute treatment of gastric ulcers? A meta-analysis of randomized clinical trials. BMC Gastroenterol. Tunis SR, Sheinhait IA, Schmid CH, et al. Lansoprazole compared with histamine 2-receptor antagonists in healing gastric ulcers: a meta-analysis. Clin Ther. Echizen H. The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet. Poynard T, Lemaire M, Agostini H. Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer. Tildesley G, Ehsanullah RS, Wood JR. Ranitidine in the treatment of gastric and duodenal ulcers associated with non-steroidal anti-inflammatory drugs. Br J Rheumatol. Agrawal NM, Campbell DR, Safdi MA, NSAID-Associated Gastric Ulcer Study Group, et al. Superiority of lansoprazole vs ranitidine in healing nonsteroidal anti-inflammatory drug-associated gastric ulcers: results of a double-blind, randomized, multicenter study. Arch Intern Med. Hawkey CJ, Karrasch JA, Szczepañski L, Omeprazole vs. Misoprostol for NSAID-induced Ulcer Management OMNIUM Group, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Chan FK, To KF, Wu JC, et al. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial. Vergara M, Catalan M, Gisbert JP, et al. Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users. Tang CL, Ye F, Liu W, et al. Eradication of Helicobacter pylori infection reduces the incidence of peptic ulcer disease in patients using nonsteroidal anti-inflammatory drugs: a meta-analysis. Koch M. Non-steroidal anti-inflammatory drug gastropathy: clinical results with misoprostol. Ital J Gastroenterol Hepatol. Bianchi Porro G, Lazzaroni M, Petrillo M, et al. Prevention of gastroduodenal damage with omeprazole in patients receiving continuous NSAIDs treatment: a double blind placebo controlled study. Taha AS, Hudson N, Hawkey CJ, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. Scally B, Emberson JR, Spata E, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. Koch M, Deiz A, Tarquini M, et al. Prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury: risk factors for serious complications. Digest Liver Dis. Article CAS Google Scholar. Sugano K, Kontani T, Katsuo S, et al. Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug NSAID therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial. Sugano K, Kinoshita Y, Miwa H, Esomeprazole NSAID Preventive Study Group, et al. Randomised clinical trial: esomeprazole for the prevention of nonsteroidal anti-inflammatory drug-related peptic ulcers in Japanese patients. Chan FK, Wong VW, Suen BY, et al. Combination of a cyclooxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial. Masclee GM, Valkhoff VE, Coloma PM, et al. Risk of upper gastrointestinal bleeding from different drug combinations. Vonkeman HE, Fernandes RW, van der Palen J, et al. Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study. Arthritis Res Ther. Emery P, Zeidler H, Kvien TK, et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomized double-blind comparison. Laine L, Harper S, Simon T, et al. A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis: Rofecoxib Osteoarthritis Endoscopy Study Group. Pavelka K, Recker DP, Verburg KM. Valdecoxib is as effective as diclofenac in the management of rheumatoid arthritis with a lower incidence of gastroduodenal ulcers: results of a week trial. Sakamoto C, Kawai T, Nakamura S, et al. Comparison of gastroduodenal ulcer incidence in healthy Japanese subjects taking celecoxib or loxoprofen evaluated by endoscopy: a placebo-controlled, double-blind 2-week study. Goldstein JL, Kivitz AJ, Verburg KM, et al. A comparison of the upper gastrointestinal mucosal effects of valdecoxib, naproxen and placebo in healthy elderly subjects. Feng GS, Ma JL, Wong BC, et al. Celecoxib-related gastroduodenal ulcer and cardiovascular events in a randomized trial for gastric cancer prevention. Yuan JQ, Tsoi KK, Yang M, et al. Systematic review with network meta-analysis: comparative effectiveness and safety of strategies for preventing NSAID-associated gastrointestinal toxicity. Liu CP, Chen WC, Lai KH, et al. Esomeprazole alone compared with esomeprazole plus aspirin for the treatment of aspirin-related peptic ulcers. Tricco AC, Alateeq A, Tashkandi M, et al. Histamine H2 receptor antagonists for decreasing gastrointestinal harms in adults using acetylsalicylic acid: systematic review and meta-analysis. Open Med. PubMed PubMed Central Google Scholar. Mo C, Sun G, Lu ML, et al. Proton pump inhibitors in prevention of low-dose aspirin-associated upper gastrointestinal injuries. Mo C, Sun G, Wang Y, et al. PPI versus histamine H2 receptor antagonists for prevention of upper gastrointestinal injury associated with low-dose aspirin: Systematic review and meta-analysis. PLoS ONE. Chan FK, Kyaw M, Tanigawa T, et al. Similar efficacy of proton-pump inhibitors vs H2-receptor antagonists in reducing risk of upper gastrointestinal bleeding or ulcers in high-risk users of low-dose aspirin. Ng FH, Wong SY, Lam KF, et al. Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Lanas A, Wu P, Medin J, et al. Low doses of acetylsaiicyiic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin Gastroenterol Hepatol. Yano H, Tsukahara K, Morita S, et al. Influence of omeprazole and famotidine on the antiplatelet effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes: a prospective, randomized, multicenter study. Circ J. Wang Z, Yang X, Cai J, et al. Influence of different proton pump inhibitors on platelet function in acute myocardial infarction patients receiving clopidogrel treatment after percutaneous coronary intervention. Biomed Res. Google Scholar. Tunggal P, Ng FH, Lam KF, et al. Effect of esomeprazole versus famotidine on platelet inhibition by clopidogrel: a double-blind, randomized trial. Am Heart J. Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recurrence of ulcer complications from long-term low-dose aspirin use. Sugano K, Matsumoto Y, Itabashi T, et al. Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trial. Sanuki T, Fujita T, Kutsumi H, Case Study Group, et al. Rabeprazole reduces the recurrence risk of peptic ulcers associated with low-dose aspirin in patients with cardiovascular or cerebrovascular disease: a prospective randomized active-controlled trial. Iwakiri R, Higuchi K, Kato M, et al. Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low-dose aspirin. Sugano K, Choi MG, Lin JT, on behalf of the LAVENDER Study Group, et al. Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER study. Taha AS, McCloskey C, Prasad R, et al. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin FAMOUS : a phase III, randomised, double-blind, placebo-controlled trial. Takeuchi T, Ota K, Harada S, et al. Comparison of teprenone and famotidine against gastroduodenal mucosal damage in patients taking low-dose aspirin. Scheiman JM, Devereaux PJ, Herlitz J, et al. Prevention of peptic ulcers with esomeprazole in patients at risk of ulcer development treated with low-dose acetylsalicylic acid: a randomised, controlled trial OBERON. Laine L, Maller ES, Yu C, et al. Ulcer formation with low-dose enteric-coated aspirin and the effect of COX-2 selective inhibition: a double-blind trial. Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin. Goldstein J, Lowry SC, Lanza FL, et al. The impact of low-dose aspirin on endoscopic gastric and duodenal ulcer rates in users of a non-selective non-steroidal anti-inflammatory drug or a cyclo-oxygenaseselective inhibitor. Goldstein JL, Cryer B, Amer F, et al. Celecoxib plus aspirin versus naproxen and lansoprazole plus aspirin: a randomized, double-blind, endoscopic trial. Chan FKL, Ching JYL, Tse YK, et al. Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding CONCERN : an industry-independent, double-blind, double-dummy, randomised trial. Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. Mcgettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. Lanza FL, Chan FKL, Quigley EMM. Guidelines for prevention of NSAID-related ulcer complications. PubMed Google Scholar. Goldstein JL, Huang B, Amer F, et al. Ulcer recurrence in high-risk patients receiving nonsteroidal anti-inflammatory drugs plus low-dose aspirin: results of a post Hoc subanalysis. Goldstein JL, Hochberg MC, Fort JG, et al. Clinical trial: the incidence of NSAID-associated endoscopic gastric ulcers in patients treated with PN naproxen plus esomeprazole magnesium vs. enteric-coated naproxen alone. Mcoll KEL, LE- Nujumi AM, Chittajallu RS, et al. A study of the pathogenesis of Helicobacter pylori negative chronic duodenal ulceration. Kanno T, Iijima K, Abe Y, et al. Helicobacter pylori -negative and non-steroidal anti-inflammatory drugs-negative idiopathic peptic ulcers show refractoriness and high recurrence incidence: multicenter follow-up study of peptic ulcers in Japan. Wong GL, Wong VW, Chan Y, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori -negative idiopathic bleeding ulcers. Wong GLH, Lau LHS, Ching JYL, et al. In contrast, only misoprostol prevents the development of NSAID-induced gastric and duodenal ulcers. Such pharmacological observations suggest that the pathophysiologic mechanisms for the induction of NSAID-induced gastric ulcer are distinctly different from those of NSAID-induced duodenal ulcers. Mild diarrhea and GI intolerance were the predominant adverse reactions experienced by patients receiving synthetic PGEs, particularly enprostil and arbaprostil. From the published data, we conclude that misoprostol is the only anti-ulcer drug proven to be well tolerated and effective for the treatment and prevention of NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAIDs therapy. Abstract Nonsteroidal anti-inflammatory drugs NSAIDs are most frequently used for the treatment of rheumatic disease due to their anti-inflammatory and analgesic properties. Bombardier C, Laine L, Reicin A, et al. VIGOR Study Group. N Engl J Med , — Mamdani M, Juurlink DN, Kopp A, et al. BMJ , — Deeks JJ, Smith LA, Bradley MD: Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomized controlled trials. BMJ , Farkouh ME, Kirshner H, Harrington RA, et al. Lancet , — Antman EM, Bennett JS, Daugherty A, et al. Circulation , — Scheiman JM, Fendrick AM: Summing the risks of NSAID therapy. Grosser T, Fries S, FitzGerald GA: Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest , 4— Jüni P, Nartey L, Reichenbach S, et al. Bresalier RS, Sandler RS, Quan H, et al. Nussmeier NA, Whelton AA, Brown MT, et al. Solomon SD, McMurray JJ, Pfeffer MA, et al. Arber N, Eagle CJ, Spicak J, for the PreSAP Trial Investigators: Celecoxib for the prevention of colorectal adenomatous polyps. PRECISION: Prospective randomized evaluation of celecoxib integrated safety vs ibuprofen or naproxen. Accessed April 25, Kearney PM, Baigent C, Godwin J, et al. Meta-analysis of randomised trials. PLoS Clin Trials , 1: e Article Google Scholar. Silverstein FE, Graham DY, Senior JR, et al. Hawkey CJ, Karrasch JA, Szczepanski L, et al. Graham DY, Agrawal NM, Campbell DR, et al. Chan FK, Hung LC, Suen BY, et al. Scheiman JM, Yeomans ND, Talley NJ, et al. Am J Gastroenterol , — Chan FK, Wong VW, Suen BY, et al. Lanas A, García-Rodríguez LA, Arroyo MT, et al. Ray WA, Chung CP, Stein CM, et al. Spiegel BM, Chiou CF, Ofman JJ: Minimizing complications from nonsteroidal antiinflammatory drugs: cost-effectiveness of competing strategies in varying risk groups. Arthritis Rheum , — Download references. Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, , USA. You can also search for this author in PubMed Google Scholar. Correspondence to James M. Reprints and permissions. Scheiman, J. |
Preventing NSAID-induced ulcers -
Symptoms were assessed on a daily basis by patient diary, where patients recorded episodes of daytime and nighttime abdominal pain defined as none, mild, moderate, or severe , study drug and NSAID dosing information, and frequency of antacid consumption.
Endoscopy with biopsy was performed each month for 3 consecutive months to determine the presence of a gastric ulcer s. Esophageal and duodenal mucosa were also evaluated.
Statistical analyses were conducted using statistical software SAS version 6. Per-protocol and intent-to-treat analyses were conducted for ulcer occurrence, abdominal pain, and antacid use, the latter 2 based on patient daily diary data.
For all efficacy and safety end points, pairwise comparisons were made between treatment groups. The comparability of the treatment groups at baseline was assessed with respect to demographic variables using the χ 2 test F test for age and medical and social histories by the Fisher exact test. Baseline severity of symptoms, based on an investigator interview, was compared among the treatment groups using the Cochran-Mantel-Haenszel method for ordered response variables.
Life table methods were used to estimate the ulcer incidence rates. The life table analysis of time to ulcer occurrence was performed using the Cochran-Mantel-Haenszel method to test treatment differences between groups.
Factors including age; sex; race; treatment for an acute NSAID-associated gastric ulcer immediately before study enrollment; hiatal hernia; investigator; alcohol, tobacco, or caffeine use; and acute baseline gastric ulcer size measured during a screening endoscopy conducted when the subject participated in a previous healing study were controlled for in the analysis.
The treatment groups were compared with respect to percentage of days with and average severity of daytime and nighttime abdominal pain and amount of antacid use based on diary data using the Wilcoxon 2-sample test. The Fisher exact test was used to compare the incidence of treatment-related adverse events defined as possibly or probably related between the treatment groups.
Two patients 1 each in the placebo and mg lansoprazole groups who did not take study medication were not included in the intent-to-treat analysis of ulcer occurrence or adverse events Table 1.
Three patients were excluded in 2 categories but were counted once in the total of 82 excluded patients. The treatment groups were well matched at baseline, including demographic characteristics, social history, previous history of gastrointestinal disorders, recent treatment for an NSAID-associated gastric ulcer, and severity of symptoms Table 2.
Most patients reported no daytime or nighttime abdominal pain at baseline. The distribution across treatment groups was similar. Patients could have taken more than 1 NSAID. These observations were unaffected after adjustment for potentially influential factors, including age, sex, race, treatment for an acute NSAID-associated gastric ulcer before study enrollment, hiatal hernia, investigator, and alcohol, tobacco, or caffeine use.
There were no statistically significant differences between any of the active treatment groups after adjusting for acute baseline gastric ulcer size. Similar trends were observed in the results of the intent-to-treat analysis of gastric ulcer prevention data throughout the week treatment period.
Absence of a gastric ulcer after 8 or 12 weeks of treatment was different among those receiving placebo, misoprostol, or lansoprazole.
There was no statistical difference between any 2 of the active treatments for time to occurrence of gastroduodenal ulcers Figure 2. To evaluate the impact of the early patient withdrawals from the misoprostol group, the worst-case scenario, where patients who withdrew from the study prematurely eg, because of an adverse event were classified as a treatment failure eg, equivalent to having a gastric ulcer , was evaluated.
Lansoprazole-treated patients experienced significantly less severe and significantly fewer days with daytime abdominal pain than evaluable misoprostol-treated patients based on analyses of patient diaries Table 3.
Similar trends were observed in the results of the intent-to-treat analysis of diary data throughout the week treatment period. One patient in the mg lansoprazole group experienced an upper gastrointestinal tract hemorrhage during the study.
Studies designed to evaluate ulcer prevention among long-term users of NSAIDs have varied regarding study design, data analysis, and results presented. Several trials with antisecretory drugs showed the outcome differed with gastric ulcers compared with duodenal ulcers and H pylori —infected ulcers compared with ulcers not infected with H pylori.
That is unfortunate since randomization would have ensured that if there were a difference in outcome in relation to H pylori status, the overall results of the study would not hinge on the proportion of patients with or without the infection.
A study conducted in Hong Kong of patients with bleeding ulcers who were long-term users of NSAIDs shows the importance of this stratification.
Among those with H pylori infection, misoprostol was similar to omeprazole 5. The present study was designed to avoid those shortcomings by comparing 2 doses of a proton pump inhibitor lansoprazole with the full therapeutic dose of misoprostol and placebo in patients with unequivocal NSAID-associated ulcers.
As with omeprazole, lansoprazole was superior to placebo, with no evidence of a major dose response effect. We confirmed that gastric ulcers recurred during the week follow-up in a greater percentage of patients receiving placebo compared with those receiving lansoprazole or misoprostol.
The results with gastroduodenal ulcer retained the same rank order. These conclusions appear to be in sharp contrast to the reported poor overall results of misoprostol vs omeprazole in the OMNIUM study. To claim superiority, the OMNIUM study also included end points other than ulcer prevention eg, the presence of heartburn to obtain "superiority.
Endoscopic ulcer prevention does not necessarily equate with prevention of ulcer complications. In that study, a history of peptic ulcer or ulcer-related bleeding was an important prognostic factor for identifying those who would develop ulcer complications and currently would prompt a test-and-treat strategy with regard to H pylori infection.
Whether this would have influenced outcome is not known. Thus, failure to identify and treat H pylori infection in the MUCOSA study may have biased the outcome. Studies are needed to test whether a proton pump inhibitor can prevent life-threatening ulcer complications among long-term users of NSAIDs.
Because misoprostol and antisecretory drugs act by different mechanisms and low-dose misoprostol is better tolerated than full-dose therapy but has a lower rate of protection , 12 the combination of low-dose misoprostol and a proton pump inhibitor might provide optimum results.
However, such studies are unlikely to be conducted if the COX-2 inhibitors prove to eliminate life-threatening NSAID ulcer complications. This study also showed that lansoprazole has several theoretical and practical advantages over misoprostol, including once-a-day dosing and lack of adverse effects.
Compliance is a significant problem with misoprostol because full dosage requires 4-times-daily dosing, and the proportion with gastrointestinal adverse effects is dose dependent.
This observation was demonstrated in this study: compliance with misoprostol was significantly inferior to that with lansoprazole. When the effect of noncompliance on ulcer development was considered, the percentage of patients remaining free from gastroduodenal ulcer disease was approximately 2-fold higher with active treatment vs placebo.
As expected, noncompliance was less of a problem with misoprostol in the OMNIUM study, because a lower dose was used. Dr Agrawal is engaged in research activities supported by Pharmacia Bridgewater, NJ , Pfizer Inc New York, NY , and TAP Pharmaceuticals.
Dr Campbell is engaged in research activities supported by AstraZenica Wilmington, Del , Merck, TAP Pharmaceuticals, Wyeth-Ayerst Philadelphia, Pa , and Janssen Pharmaceutica Titusville, NJ. Presented at Digestive Disease Week and the th Annual Meeting of the American Gastroenterological Association, Orlando, Fla, May , Dr Haber performed the histologic and H pylori analyses for this study.
Ms Collis managed study operations and authored the clinical report. Ms Lukasik oversaw study operations and authored the clinical report. Dr Huang conducted the statistical analyses of data for this study. We thank TAP Pharmaceutical Products Inc for their support of this research project and Sandra Norris, PharmD, for her help with the manuscript.
Naurang M. Agrawal, MD, Durham, NC; Robert J. Bailey, MD, Alberta, Canada; Charles F. Barish, MD, Raleigh, NC; Thomas Bianchi, MD, Tallassee, Ala; Charles Allen Birbara, MD, Worcester, Mass; Phillip C. Bird, MD, Norman, Okla; Joel Block, MD, Chicago, Ill; Kevin Block, MD, Madison, Wis; Jeffrey R.
Breiter, MD, Manchester, Conn; Jacques Caldwell, MD, Gainesville, Fla; Donald R. Campbell, MD, Kansas City, Mo; Stuart Chen, MD, Kansas City; Charles L. Collip, MD, Portland, Ore; Carleton Davis, MD, Monroe, Wis; Francis Dega, MD, Boise, Idaho; Jacinto DelMazo, MD, Atlanta, Ga; Michael DeMicco, MD, Anaheim, Calif; James T.
Doyle, MD, Spokane, Wash; Margaret Drehobl, MD, San Diego, Calif; Sudhir K. Dutta, MD, Baltimore, Md; Raymond Federman, MD, Akron, Ohio; Roy Fleischman, MD, Dallas, Tex; Fred C. Fowler, MD, Charlotte, NC; Syam P. Gaddam, MD, Garden Grove, Calif; William Harford, MD, Dallas; W.
John Henry, MD, Greer, SC; Samuel Ho, MD, Minneapolis, Minn; Keith P. Hussey, MD, Naples, Fla; David S. Probiotics is another approach in modulating the composition of intestinal flora and has been used in treating several GI disorders like inflammatory bowel diseases, 78 irritable bowel syndrome, 79 infectious diarrhea and antibiotic-induced diarrhea.
NSAID-induced small bowel injury in rats could be alleviated after restoring small intestinal Actinobacteria through administration of selected commensal bacteria during treatment with PPI and NSAIDs. Gastroprotective agents, especially PPIs, are typically co-prescribed to protect the upper GI tract from NSAIDs induced mucosal injury, which was also recommended by guidelines.
Rebamipide, an amino acid derivative of 2- 1H -quinolinone, is a mucosal protective drug that has been clinically used for treating gastritis and peptic ulcers. Small RCTs of healthy subjects supported that rebamipide had the potential to reduce NSAID-induced small intestinal injury.
Another small multicenter study by Watanabe et al. However, Ota et al. A systematic review and meta-analysis 34 including 15 RCTs and individuals, provided consistent results that rebamipide is effective and safe for defending against NSAID-induced lower GI injuries.
However, most studies are with small sample size and short-term follow-up. Irsogladine, a phosphodiesterase inhibitor, is currently used as one of the anti-ulcer or gastroprotective agents for the treatment of gastric ulcer and gastritis.
The study by Kuramoto et al. The result was consistent in the study of Isomura et al. Irsogladine also presented treatment effects which significantly decreased the number of small intestinal lesions induced by NSAIDs.
Apart from the above agents, there are several other drugs such as sulphasalazine, 42 ecabet sodium, 43 egualen sodium, 44 curcumin, 95 , 96 and muscovite, 45 which were reported to have a preventive effect on NSAIDs-induced small intestine injury.
However, data is very limited for these agents. So far, effective prevention and treatment of NSAID-associated lower GI injury are lacking.
Though various agents including selective COX inhibitors, misoprostol, antibiotics and mucoprotective agents have been considered as candidates for NSAID-induced intestinal injury, they are not properly evaluated in clinical trials. High-quality well-designed randomized, placebo-controlled trials with long-term follow up are needed to verify the efficacy of potential agents in preventing NSAID-associated lower intestinal injury.
NSAIDs, nonsteroidal anti-inflammatory drugs; GI, gastrointestinal; RCT, randomized controlled trial; qd, one a day; bid, twice a day; tid, 3 times a day; qid, 4 times a day; RR, relative risk; CI, confidence interval; RA, rheumatoid arthritis; OA, osteoarthritis; HR, hazard ratio; PPI, proton pump inhibitor; EDTA, ethylenediamine tetraacetic acid; FCCs, faecal calprotectin concentrations; H2RA, histamine type-2 receptor antagonists; LDA, low-dose aspirin.
Table 1 Summary of Studies on the Different Interventions to Prevent NSAID-Induced Lower GI Injuries. pISSN eISSN Menu Search Search Submission Metrics My read Subscription Help Help Search. Help 1. Aims and Scope Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology.
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Search Clear. Year - Select- to - Select -. Split Viewer. Potential Strategies in the Prevention of Nonsteroidal Anti-inflammatory Drugs-Associated Adverse Effects in the Lower Gastrointestinal Tract Chuan-Guo Guo , Wai K.
Received : June 15, ; Accepted : July 9, Rebamipide Rebamipide, an amino acid derivative of 2- 1H -quinolinone, is a mucosal protective drug that has been clinically used for treating gastritis and peptic ulcers. Irsogladine Irsogladine, a phosphodiesterase inhibitor, is currently used as one of the anti-ulcer or gastroprotective agents for the treatment of gastric ulcer and gastritis.
Other Apart from the above agents, there are several other drugs such as sulphasalazine, 42 ecabet sodium, 43 egualen sodium, 44 curcumin, 95 , 96 and muscovite, 45 which were reported to have a preventive effect on NSAIDs-induced small intestine injury.
No potential conflict of interest relevant to this article was reported. Table 1 Summary of Studies on the Different Interventions to Prevent NSAID-Induced Lower GI Injuries Author year Study design Intervention Study period Subject Main result Selective COX-2 inhibitors Goldstein et al. Hawkey et al.
Laine et al. Chan et al. Jarupongprapa et al. Misoprostol Bjarnason et al. Davies et al. Morris et al. Raskin et al. Rostom et al. Fujimori et al. Kyaw et al.
Taha et al. COX-inhibiting nitric oxide donors Hawkey et al. Naproxen increased intestinal permeability whereas AZD and placebo did not. Fiorucci et al. However, NCX causes less gastric damage and prevents monocyte activation. Lohmander et al.
Most secondary endoscopic GI end points favored AZD Intestinal microbiota modulation Bjarnason et al. There were no significant changes in intestinal permeability, or endoscopic or microscopic appearances of the gastroduodenal mucosa. Montalto et al. Endo et al. casei group or control group 3 mo 25 Aspirin users with unexplained iron deficiency anemia Significant decreases in the number of mucosal breaks and the capsule endoscopy score were observed at the 3-mo evaluation in the L.
Mucoprotective agents Niwa et al. Thong-Ngam et al. For subjects with mucosal injuries, rebamipide tended to decrease mucosal injuries from 25 in the control to 8.
Mizukami et al. Zhang et al. Rebamipide showed a beneficial effect against the small bowel damage RR, 2. Kurokawa et al. Ota et al. The gastroscopic and capsule endoscopic findings and the fecal occult blood test findings did not differ significantly among three groups. Kuramoto et al.
Isomura et al. Kojima et al. Shim et al. However, 2 cases of peptic ulcer in the placebo group but none in the test group were observed. Other Hayllar et al. Iguchi et al. Huang et al.
Co-administration of muscovite reduced the rate of mucosal break to Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal anti-inflammatory drug use.
Am J Gastroenterol ; Lanas Á, Carrera-Lasfuentes P, Arguedas Y, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol ; Laine L, Curtis SP, Langman M, et al.
Lower gastrointestinal events in a double-blind trial of the cyclo-oxygenase-2 selective inhibitor etoricoxib and the traditional nonsteroidal anti-inflammatory drug diclofenac.
Gastroenterology ; Lanas A, García-Rodríguez LA, Polo-Tomás M, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Lanas A, Sopeña F. Nonsteroidal anti-inflammatory drugs and lower gastrointestinal complications.
Gastroenterol Clin North Am ; Wallace JL. NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies. Br J Pharmacol ; Chan FK.
NSAID-associated lower gastrointestinal bleeding: where do we stand?. Lanza FL, Chan FK, Quigley EM; Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications.
Goldstein JL, Eisen GM, Lewis B, et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy.
Aliment Pharmacol Ther ; Hawkey CJ, Ell C, Simon B, et al. Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole. Laine L, Connors LG, Reicin A, et al.
Serious lower gastrointestinal clinical events with nonselective NSAID or coxib use. Chan FK, Lanas A, Scheiman J, Berger MF, Nguyen H, Goldstein JL. Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis CONDOR : a randomised trial. Lancet ; Jarupongprapa S, Ussavasodhi P, Katchamart W.
Comparison of gastrointestinal adverse effects between cyclooxygenase-2 inhibitors and non-selective, non-steroidal anti-inflammatory drugs plus proton pump inhibitors: a systematic review and meta-analysis.
J Gastroenterol ; Bjarnason I, Smethurst P, Fenn CG, Lee CE, Menzies IS, Levi AJ. Misoprostol reduces indomethacin-induced changes in human small intestinal permeability.
Dig Dis Sci ; Davies GR, Wilkie ME, Rampton DS. Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability. Morris AJ, Murray L, Sturrock RD, Madhok R, Capell HA, Mackenzie JF.
Short report: the effect of misoprostol on the anaemia of NSAID enteropathy. Raskin JB, White RH, Jackson JE, et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med ; Rostom A, Dube C, Wells G, et al.
Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev ;4:CD Watanabe T, Sugimori S, Kameda N, et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol: a pilot study.
Fujimori S, Seo T, Gudis K, et al. Prevention of nonsteroidal anti-inflammatory drug-induced small-intestinal injury by prostaglandin: a pilot randomized controlled trial evaluated by capsule endoscopy.
Gastrointest Endosc ; Kyaw MH, Otani K, Ching JYL, et al. Misoprostol heals small bowel ulcers in aspirin users with small bowel bleeding. Taha AS, McCloskey C, McSkimming P, McConnachie A. Misoprostol for small bowel ulcers in patients with obscure bleeding taking aspirin and non-steroidal anti-inflammatory drugs MASTERS : a randomised, double-blind, placebo-controlled, phase 3 trial.
Lancet Gastroenterol Hepatol ; Hawkey CJ, Jones JI, Atherton CT, et al. Gastrointestinal safety of AZD, a cyclooxygenase inhibiting nitric oxide donator: proof of concept study in humans. Gut ; Fiorucci S, Mencarelli A, Meneguzzi A, et al. Co-administration of nitric oxide-aspirin NCX and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans.
J Am Coll Cardiol ; Lohmander LS, McKeith D, Svensson O, et al. A randomised, placebo controlled, comparative trial of the gastrointestinal safety and efficacy of AZD versus naproxen in osteoarthritis. Ann Rheum Dis ; Bjarnason I, Hayllar J, Smethurst P, Price A, Gumpel MJ.
Non-steroidal anti-inflammatory drugs NSAIDs are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe.
However, there is overwhelming evidence linking these agents to a variety of gastrointestinal GI toxicities. To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity.
We searched MEDLINE from to May , Current Contents for six months prior to May , EMBASE to May , and the Cochrane Controlled Trials Register from to May Recent conference proceedings were reviewed and content experts and companies were contacted.
Randomized controlled clinical trials RCTs of prostaglandin analogues PA , H2-receptor antagonists H2RA or proton pump inhibitors PPI for the prevention of chronic NSAID induced upper GI toxicity were included.
Two independent authors extracted data regarding population characteristics, study design, methodological quality and number of participants with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop outs due to symptoms.
Dichotomous data were pooled using RevMan 5. Heterogeneity was evaluated using a chi square test, and the I square statistic. Forty-one RCTs met the inclusion criteria.
Gut and Liver NSAID--induced an international journal Thermogenic pre-workout formulas gastroenterology, focusing on Black pepper extract for cognitive function gastrointestinal Preventng, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on Preventing NSAID-induced ulcers clinical and research-based NSAID-induces in gastroenterology. The Ulcerx publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal.
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