Prevention Of Recurrent Ulcer Bleeding Research Articles

Prevention of recurrent idiopathic gastroduodenal ulcer bleeding: a double-blind, randomised trial

ObjectivePatients with a history of Helicobacter pylori-negative idiopathic bleeding ulcers have a considerable risk of recurrent ulcer complications. We hypothesised that a proton pump inhibitor (lansoprazole) is superior to a...

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

Present guidelines are conflicting for patients at high risk of both cardiovascular and gastrointestinal events who continue to require non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2-selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous ulcer bleeding. For this industry-independent, double-blind, double-dummy, randomised trial done in one academic hospital in Hong Kong, we screened patients with arthritis and cardiothrombotic diseases who were presenting with upper gastrointestinal bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing, an independent staff member randomly assigned (1:1) patients who were negative for Helicobacter pylori with a computer-generated list of random numbers to receive oral administrations of either celecoxib 100 mg twice per day plus esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg once per day. Both patients and investigators were masked to their treatments. The primary endpoint was recurrent upper gastrointestinal bleeding within 18 months. The primary endpoint and secondary safety endpoints were analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT00153660. Between May 24, 2005, and Nov 28, 2012, we enrolled 514 patients, assigning 257 patients to each study group, all of whom were included in the intention-to-treat population. Recurrent upper gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group (25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18 months was 5·6% (95% CI 3·3-9·2) in the celecoxib group and 12·3% (8·8-17·1) in the naproxen group (p=0·008; crude hazard ratio 0·44, 95% CI 0·23-0·82; p=0·010). Excluding patients who reached study endpoints, 21 (8%) patients in the celecoxib group and 17 (7%) patients in the naproxen group had adverse events leading to discontinuation of treatment. No treatment-related deaths occurred during the study. In patients at high risk of both cardiovascular and gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived cardiovascular safety. The Research Grant Council of Hong Kong.

814 Prevention of Recurrent Ulcer Bleeding in Arthritis Patients With High Cardiovascular and High Gastrointestinal Risks: A 18-Month, Double-Blind, Randomized Trial

814 Prevention of Recurrent Ulcer Bleeding in Arthritis Patients With High Cardiovascular and High Gastrointestinal Risks: A 18-Month, Double-Blind, Randomized Trial

Sa1132 Proton-Pump Inhibitor (PPI) Versus Histamine-2 Receptor Antagonist (H2RA) for the Prevention of Recurrent Upper Gastrointestinal Bleeding (UGI) in High-Risk Users of Low-Dose Aspirin (ASA): An Interim Analysis

BACKGROUND Previously we showed that PPI prevented recurrent UGI bleeding in ASA users with a history of UGI bleeding. Whether histamine-2 receptor antagonists (H2RAs) are an effective gastroprotective agent in these high-risk ASA users is unclear. We compared a PPI with an H2RA for prevention of recurrent ulcer bleeding with ASA. METHODS This was a 12-month, double-blind, randomized trial of rabeprazole versus famotidine in ASA users with a history of endoscopically confirmed nonvariceal UGI bleeding. After their ulcers had healed, we randomly assigned ASA users (80 mg once daily) with negative tests for Helicobacter pylori to receive either 20 mg of rabeprazole once daily or 40 mg of famotidine once daily for up to 12 months. Endoscopy was repeated if they developed symptoms of recurrent GI bleeding, had a drop in hemoglobin (Hb) >2 g/dL, withdrew early due to

COMPARISON OF ADJUVANT THERAPIES BY AN H2‐RECEPTOR ANTAGONIST AND A PROTON PUMP INHIBITOR AFTER ENDOSCOPIC TREATMENT IN HEMOSTATIC MANAGEMENT OF BLEEDING GASTRODUODENAL ULCERS

Upper gastrointestinal bleeding is often associated with a higher risk of serious blood loss. Both H2-receptor antagonists and proton pump inhibitors are commonly given intravenously for endoscopic hemostatic therapies. We compared the effects of a H2-receptor antagonist (famotidine) and a proton pump inhibitor (omeprazole) injected during the early phase (the first 3 days) on cessation of bleeding and prevention of its recurrence in patients who underwent endoscopic therapy for gastroduodenal ulcer bleeding. Consecutive patients who were hospitalized at our clinic with bleeding gastroduodenal ulcers and underwent endoscopic therapy were randomly assigned to receive injections of famotidine, omeprazole, or both. Injection of acid suppressants was switched on the fourth day to the oral administration of omeprazole continued for 8 weeks. Over a 25-month period, 116 patients were enrolled. The overall success rate for endoscopic hemostasis was 115/116 (99.1%). The success rate of hemostasis and prevention of recurrent ulcer bleeding by type of acid suppressant following endoscopic hemostasis was 39/40 (97.5%) for Group 1 (3-day omeprazole administration), 35/37 (94.6%) for Group 2 (3-day famotidine administration), and 38/39 (97.4%) for Group 3 (1-day famotidine and then 2-day omeprazole administration), yielding an overall rate of 112/116 (96.6%). No significant difference in the hemostatic effect was observed among the groups. There were also no differences in the duration of hospital days and the number of fasting days between the three groups. Famotidine and omeprazole injected during the early phase of a bleeding ulcer may have similar effects to an adjuvant therapy for preventing rebleeding from endoscopically treated upper gastrointestinal bleeding in Japanese patients.

Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial

Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial

Celecoxib combined with esomeprazole prevented recurrent ulcer bleeding in patients with previous NSAID-induced ulcer bleeding

Source Citation Chan FK, Wong VW, Suen BY, et al. Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: ...

Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial

Guidelines on pain management recommend that patients at risk of ulcers receive either a cyclo-oxygenase (COX 2) inhibitor or a non-steroidal anti-inflammatory drug (NSAID) with a proton-pump inhibitor (PPI). These two treatments have similar effectiveness, but they are insufficient for protection of patients at very high risk for ulcer bleeding. We aimed to test the hypothesis that in patients with previous ulcer bleeding induced by non-selective NSAIDs, combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole would be better than celecoxib alone for prevention of recurrent ulcer bleeding. 441 consecutively presenting patients who were taking non-selective NSAIDs for arthritis were recruited to our single-centre, prospective, randomised, double-blind trial after admission to hospital with upper-gastrointestinal bleeding. Patients were enrolled after their ulcers had healed and a histological test for Helicobacter pylori was negative. All patients were given 200 mg celecoxib twice daily. 137 patients were randomly assigned to receive 20 mg esomeprazole twice daily (combined-treatment group), and 136 to receive a placebo (control group) for 12 months. The primary endpoint was recurrent ulcer bleeding during treatment or within 1 month of the end of treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00365313. Combination treatment was more effective than celecoxib alone for prevention of ulcer bleeding in patients at high risk. The 13-month cumulative incidence of the primary endpoint was 0% in the combined-treatment group and 12 (8.9%) in the controls (95% CI difference, 4.1 to 13.7; p=0.0004). The median follow-up was 13 months (range 0.4-13.0). Discontinuation of treatment and the incidence of adverse events were similar in the two treatment groups. Patients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding.

Summing the risk of NSAID therapy

Reports concluding that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the likelihood of cardiovascular adverse events have led patients and clinicians to reduce use. It is intriguing to recollect that the cardiotoxicity of NSAIDs (both cyclo-oxygenase-2 [COX-2] selective inhibitors and non-selective dual inhibitors have been implicated) would not have been revealed if not for the push to market novel drugs developed to reduce the well-documented gastrointestinal complications of this widely used class. While weighing risks and benefits of interventions is an essential component of clinical decisionmaking, it has become increasingly complex to decide in whom the use of any NSAID—with or without a gastroprotective agent, and with or without concomitant aspirin—is appropriate. In view of the multiplicity, and in many cases rarity, of adverse events, it is unlikely that a single mega-trial will adequately address the numerous safety and effectiveness issues. In the meantime, careful synthesis of the literature—not complete reliance on single studies that address one outcome—is required to inform decisionmaking. This stepwise approach is crucial, because appropriate selection of an NSAID should be driven by assessment of an individual's cardiovascular and gastrointestinal risk, or both, rather than by a drug's reported rate of adverse events in heterogeneous populations (table). 1 Scheiman JM. Fendrick AM Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs. Arthritis Res Ther. 2005; 7: S23-S29 Crossref PubMed Scopus (43) Google Scholar TableClinicians guide to anti-infl ammatory therapy in 2007 No or low NSAID gastrointestinal risk NSAID gastrointestinal risk No cardiovascular risk (without aspirin) Nonselective NSAID (cost consideration) COX-2 selective inhibitor or non-selective NSAID+proton-pump inhibitor COX-2 selective inhibitor+proton-pump inhibitor for those with prior gastrointestinal bleeding Cardiovascular risk (with aspirin) Naproxen * Non-selective or selective (low-dose) inhibitor without established aspirin interaction if naproxen is ineffective.2 Proton-pump inhibitor irrespective of NSAID Addition of proton-pump inhibitor if gastrointestinal risk of aspirin/NSAID combination warrants gastroprotection Naproxen if CV risk outweighs gastrointestinal risk COX-2 selective inhibitor+proton-pump inhibitor for those with previous gastrointestinal bleeding Misoprostol at full dose (200 μg four times a day) may be substituted for proton-pump inhibitor. Adapted from 1 Scheiman JM. Fendrick AM Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs. Arthritis Res Ther. 2005; 7: S23-S29 Crossref PubMed Scopus (43) Google Scholar . * Non-selective or selective (low-dose) inhibitor without established aspirin interaction if naproxen is ineffective. 2 Grosser T Fries S Fitzgerald GA Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Cllin Invest. 2006; 116: 4-15 Crossref PubMed Scopus (822) Google Scholar Open table in a new tab Misoprostol at full dose (200 μg four times a day) may be substituted for proton-pump inhibitor. Adapted from 1 Scheiman JM. Fendrick AM Practical approaches to minimizing gastrointestinal and cardiovascular safety concerns with COX-2 inhibitors and NSAIDs. Arthritis Res Ther. 2005; 7: S23-S29 Crossref PubMed Scopus (43) Google Scholar . Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trialPatients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding. Full-Text PDF

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.