Sustained efficacy following resolution of frequent heartburn with an over-the-counter regimen of esomeprazole 20 mg or placebo for 14 days: two randomized trials.

BACKGROUND: A two-week course of therapy with an over-the-counter proton-pump inhibitor (PPI) is recommended for frequent heartburn. Limited research has been conducted on the sustained efficacy of short-term PPI therapy after treatment cessation. Esomeprazole 20 mg was evaluated in the seven-day follow-up period after the two-week treatment period using pooled data from two identical randomized, double-blind, placebo-controlled studies. METHODS: Adults without confirmed diagnoses of gastroesophageal reflux disease experiencing heartburn at least two days/week in the past four weeks were eligible. Subjects received treatment with esomeprazole 20 mg or placebo once daily for 14 days. Heartburn episodes were documented using daily diaries. Missing data during the two-week treatment period were assumed to be days with heartburn. The proportion of subjects with heartburn resolution while on treatment and during the seven days of follow-up was assessed. Predictors of resolution during this post-treatment period were evaluated using a stepwise logistic regression model. RESULTS: All subjects in the pooled analysis set who reported diary data for at least three follow-up days were analyzed (N = 584). This cut-off was used to ensure that sufficient data were collected for these analyses. Greater run-in heartburn frequency was a significant negative predictor of heartburn resolution during follow-up (P < 0.001). Among the on-treatment efficacy variables, the best predictor of resolution during follow-up was resolution during the last seven days of treatment (odds ratio: 3.81 [95% confidence interval: 2.40, 6.05; P < 0.0001]). CONCLUSIONS: Lower baseline heartburn frequency and heartburn resolution during the last seven days of treatment were associated with a greater likelihood of heartburn resolution during the seven-day follow-up. TRIAL REGISTRATION: Registered at ClinicalTrials.gov June 11, 2011: NCT01370525 ; NCT01370538 .

Bleeding after percutaneous endoscopic gastrostomy is linked to serotonin reuptake inhibitors, not aspirin or clopidogrel.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is an invasive procedure that can result in bleeding. Guidelines recommend discontinuing clopidogrel for 7 to 10 days, but not withholding aspirin, before PEG. Serotonin reuptake inhibitors (SRIs) have been associated with an increased risk of GI bleeding. OBJECTIVE: To determine whether there is an association between periprocedural aspirin, clopidogrel, or SRI use and bleeding in patients who underwent PEG tube placement. DESIGN: Retrospective cohort study. SETTING: Large quaternary-care academic medical center. PATIENTS: A total of 990 patients (525 men) with a median age of 69.8 years who underwent PEG from January 1999 to April 2009. INTERVENTIONS: PEG tube placement. MAIN OUTCOME MEASUREMENTS: GI bleeding. RESULTS: Sixteen patients (1.6%) had evidence of bleeding during the first 48 hours after PEG, and 12 patients (1.2%) had evidence of bleeding between 48 hours and 14 days after PEG. Thirty-six patients (3.6%) received high-dose aspirin (>325 mg), 27 patients (2.7%) received clopidogrel (75 mg), and 99 patients (10%) received an SRI before PEG. Twenty-four patients (2.4%) received high-dose aspirin, 25 patients (2.5%) received clopidogrel, and 130 patients (13.1%) received an SRI after PEG. Multivariate analysis demonstrated no association between periprocedural use of aspirin (at any dose) or clopidogrel and post-PEG bleeding. However, SRIs administered 24 hours or less before PEG were associated with a significantly higher odds of post-PEG bleeding (adjusted odds ratio 4.1; 95% CI, 1.1-13.4; P = .04). LIMITATIONS: Retrospective, single-center study with limited statistical power despite a relatively large cohort of patients. CONCLUSIONS: Use of aspirin or clopidogrel before or after PEG was not associated with procedure-related bleeding. SRI use in the 24 hours before PEG was associated with an increased risk of bleeding.

The value of branded proton pump inhibitors: formulary considerations.

The prevalence of gastroesophageal reflux disease (GERD) continues to rise, placing an increasing burden on our health care system. Proton pump inhibitors (PPIs) are the most effective and widely used therapy for GERD. Many PPIs are now available in generic and over-the-counter forms, and managed care formularies often choose these as their preferred drug for GERD treatment. However, newer-generation branded PPIs, as a result of differences in their pharmacokinetic and pharmacodynamic profiles, may offer clinical advantages over generic PPIs. This article discusses these differences and the advantages they offer and suggests possible ways to incorporate the newer PPIs into formularies.

Meshed capillary vessels found on narrow-band imaging without optical magnification effectively identifies colorectal neoplasia: a North American validation of the Japanese experience.

BACKGROUND: The presence of meshed capillary (MC) vessels is highly sensitive (96%) and specific (92%) for diagnosing colorectal neoplasia on colonoscopy by using narrow-band imaging (NBI) with optical magnification, which is not available in North America. However, the efficacy of NBI to identify an MC pattern without optical magnification has not been determined. OBJECTIVE: To determine the diagnostic capabilities of NBI colonoscopy without optical magnification in differentiating neoplastic from non-neoplastic colorectal polyps by using the MC pattern. DESIGN: Retrospective comparison of prospectively collected colorectal polyp data. SETTING: Large, academic medical center. PATIENTS: This study involved 126 consecutive colorectal polyps (median size 3 mm) that were found in 52 patients (33 men) with a median age of 59.5 years. INTERVENTION: All lesions identified by white-light colonoscopy were prospectively diagnosed in real-time by using the MC pattern as determined on high-definition NBI, with 1.5x zoom but without true optical magnification, and then endoscopically excised. Surgical pathology was used as the criterion standard. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of identifying neoplastic polyps were calculated. RESULTS: NBI without optical magnification was found to have a sensitivity of 93%, specificity of 88%, positive predictive value of 90%, negative predictive value of 91%, and diagnostic accuracy of 91% when all polyp sizes were considered. For lesions < or =5 mm, sensitivity was 87%, specificity was 93%, positive predictive value was 89%, negative predictive value was 91%, and diagnostic accuracy was 90%. LIMITATIONS: Single-center, single-endoscopist experience. CONCLUSION: Use of the MC pattern on NBI colonoscopy without optical magnification effectively distinguishes neoplastic from non-neoplastic colorectal polyps. NBI colonoscopy without optical magnification for neoplastic polyp diagnosis appears to be comparable with NBI with optical magnification when the MC pattern is used. A large, prospective trial is needed for further validation.

Helicobacter pylori-negative gastritis in erosive esophagitis, nonerosive reflux disease or functional dyspepsia patients.

BACKGROUND: Although Helicobacter pylori infection is believed to be the main cause of chronic gastritis, a US clinical trial investigating the long-term effects of lansoprazole as maintenance therapy for erosive esophagitis revealed a surprisingly high prevalence (over 90%) and severity of chronic gastritis in H. pylori-negative subjects. GOALS: This study aims to compare prevalence and severity of chronic gastritis of the body and antrum in H. pylori-negative subjects with erosive esophagitis, nonerosive reflux disease, or functional dyspepsia from several trials. STUDY: Pretreatment gastric histology was compared in 1595 H. pylori-negative subjects with erosive esophagitis (>or= grade 2; n=196), nonerosive reflux disease (n=688), or functional dyspepsia (n=711) who participated in US Takeda-sponsored lansoprazole trials. RESULTS: Pretreatment histology data from US clinical studies showed that 67.5% and 75.0% of H. pylori-negative adult subjects with erosive esophagitis had moderate or severe body and antral chronic gastritis, respectively. Chronic gastritis was also observed in H. pylori-negative subjects with nonerosive reflux disease or functional dyspepsia, although prevalence was significantly less (P<0.001) than in erosive esophagitis. CONCLUSIONS: Chronic gastritis in H. pylori-negative subjects is more common than previously appreciated. These results highlight the need for better characterization of gastric mucosal histology in these gastrointestinal disorders.

Long-term quality of life improvement in subjects with healed erosive esophagitis: treatment with lansoprazole.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a chronic symptomatic condition and may be associated with erosive esophagitis (EE). Considerable data on the long-term maintenance of healing of EE are available, but data on long-term GERD symptom prevention and patient quality of life (QOL) are limited. AIMS: To investigate QOL in subjects with healed EE who received 12 months of double-blind maintenance treatment with lansoprazole or ranitidine, followed by long-term open-label lansoprazole therapy to prevent recurrence of EE. METHODS: Subjects with healed EE received 12 months of double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by dose-titrated, open-label lansoprazole therapy for up to 82 months. RESULTS: During double-blind treatment (n = 206), lansoprazole-treated patients showed significantly (P

Control of gastric acid secretion in health and disease.

Recent milestones in the understanding of gastric acid secretion and treatment of acid-peptic disorders include the (1) discovery of histamine H(2)-receptors and development of histamine H(2)-receptor antagonists, (2) identification of H(+)K(+)-ATPase as the parietal cell proton pump and development of proton pump inhibitors, and (3) identification of Helicobacter pylori as the major cause of duodenal ulcer and development of effective eradication regimens. This review emphasizes the importance and relevance of gastric acid secretion and its regulation in health and disease. We review the physiology and pathophysiology of acid secretion as well as evidence regarding its inhibition in the management of acid-related clinical conditions.

Long-term efficacy of lansoprazole in preventing relapse of erosive reflux esophagitis.

In a phase III study of lansoprazole treatment, patients with healed or unhealed erosive esophagitis entered a titrated open-label treatment period and received lansoprazole for

Lansoprazole for long-term maintenance therapy of erosive esophagitis: double-blind comparison with ranitidine.

In a study evaluating the efficacy and safety of lansoprazole to prevent the relapse of erosive esophagitis (EE), 206 of 241 patients (85%) healed after open-label treatment with lansoprazole 30 mg once daily for 8 weeks and received double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily for up to 1 year. At 1 year, 67% of lansoprazole-treated and 13% of ranitidine-treated patients remained healed (P<0.001). Lansoprazole-treated patients experienced significantly greater symptom relief (P<0.001), and, if asymptomatic at entry into the maintenance phase, remained asymptomatic for significantly longer than ranitidine-treated patients (P<0.001). Symptom status correlated with healing (P=0.001), supporting the symptom-directed management of EE. Both treatments were well tolerated and no unexpected events occurred. Daily therapy with lansoprazole to prevent the relapse of EE is effective, well tolerated, and superior to ranitidine in the maintenance of healing and symptom relief.

25 Years of Proton Pump Inhibitors: A Comprehensive Review.

Proton pump inhibitors (PPIs) were clinically introduced more than 25 years ago and have since proven to be invaluable, safe, and effective agents for the management of a variety of acid-related disorders. Although all members in this class act in a similar fashion, inhibiting active parietal cell acid secretion, there are slight differences among PPIs relating to their pharmacokinetic properties, metabolism, and Food and Drug Administration (FDA)-approved clinical indications. Nevertheless, each is effective in managing gastroesophageal reflux disease and uncomplicated or complicated peptic ulcer disease. Despite their overall efficacy, PPIs do have some limitations related to their short plasma half-lives and requirement for meal-associated dosing, which can lead to breakthrough symptoms in some individuals, especially at night. Longer-acting PPIs and technology to prolong conventional PPI activity have been developed to specifically address these limitations and may improve clinical outcomes.

Managing gastroesophageal reflux disease - comparative efficacy and outcomes of dexlansoprazole MR.

The management of gastroesophageal reflux disease (GERD) has been revolutionized with the development of proton pump inhibitors (PPIs). Unfortunately, due to the inherent pharmacokinetic and pharmacodynamic profiles of conventional PPIs, many patients continue to suffer from symptoms related to GERD despite appropriate use of PPIs. Dexlansoprazole MR is a PPI with a unique dual delayed-release delivery system that has been designed to address the unmet needs in GERD management. Specifically, dexlansoprazole MR addresses limitations with short plasma half-life and need for meal-associated dosing, characteristic of conventional PPIs. In addition, dexlansoprazole MR has been shown to be effective in several specific clinical situations. These include coadministration with clopidogrel, healing of all grades of erosive esophagitis, improvement in reflux-related quality of life, step down to once-per-day dosing, and treatment of Helicobacter pylori infections. Furthermore, dexlansoprazole MR has been found to induce symptom improvement in patients with nonerosive esophageal reflux disease, nocturnal heartburn and GERD-related sleep disturbance, and regurgitation. Overall, dexlansoprazole MR is a unique and useful tool in the management of GERD.

Prevention of nonsteroidal anti-inflammatory drug-associated gastrointestinal symptoms and ulcer complications.

Nonsteroidal anti-inflammatory drugs (NSAIDs) produce symptoms of dyspepsia and peptic ulcer disease in up to 50% and up to 20%, respectively, of individuals taking them. Risk factors for NSAID-related gastric injury include age >70 years, history of ulcer disease, use of multiple agents (e.g., > or =2 NSAIDs, or an NSAID plus aspirin--even at cardioprotective doses), high doses of an NSAID, and concurrent use of corticosteroids or anticoagulants. In NSAID users, infection with Helicobacter pylori can produce additive or synergistic gastric mucosal injury. Several clinical strategies can decrease the risk for dyspepsia, ulceration, and the more serious complications in NSAID users. Proton pump inhibitor (PPI) co-therapy has been shown to lower the incidence of dyspepsia in those taking NSAIDs. In those with an active ulcer, PPI therapy produces ulcer healing even in "tough-to-treat" individuals who require ongoing NSAID therapy. Maintenance of ulcer healing is significantly greater in those who receive ongoing PPI treatment compared with placebo, and adverse events and treatment withdrawals are fewer compared with their occurrence in persons treated with misoprostol. In those not receiving aspirin therapy, the use of an NSAID that is a selective inhibitor of cyclooxygenase (COX)-2 may result in fewer gastrointestinal symptoms compared with a traditional agent; however, studies have failed to show any decrease in healthcare resource utilization (including outpatient or emergency room visits, hospitalization rate, or use of any resource) with COX-2-selective therapy.

Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials.

PURPOSE: The efficacy of proton pump inhibitor therapy for symptom resolution in patients with functional dyspepsia remains controversial. This study was designed to compare the efficacy of lansoprazole with placebo in relieving upper abdominal discomfort in patients with functional dyspepsia. METHODS: We enrolled 921 patients with functional dyspepsia (defined as persistent or recurrent upper abdominal discomfort during the prior 3 months) and moderate upper abdominal discomfort on at least 30% of screening days; none of the patients had predominant symptoms suggestive of gastroesophageal reflux or endoscopic evidence of erosive or ulcerative esophagitis, or gastric or duodenal ulcer or erosion. Patients were assigned randomly to receive lansoprazole 15 mg (n = 305), lansoprazole 30 mg (n = 308), or placebo (n = 308) daily for 8 weeks. Patients recorded the frequency and severity of symptoms in daily diaries. RESULTS: At week 8, significantly (P <0.001) greater mean reductions in the percentage of days with upper abdominal discomfort were reported in patients treated with lansoprazole 15 mg (35%) or 30 mg (34%) compared with those treated with placebo (19%). Similarly, more patients treated with lansoprazole 15 mg (44%) or 30 mg (44%) reported complete symptom resolution (defined as no episodes of upper abdominal discomfort in the 3 days before the study visit) at 8 weeks than did placebo-treated patients (29%, P <0.001). Improvement of upper abdominal discomfort, however, was seen only in patients who had at least some symptoms of heartburn at enrollment. CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn.

Gastrointestinal safety and tolerability of nonselective nonsteroidal anti-inflammatory agents and cyclooxygenase-2-selective inhibitors.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used of all drugs and are the most common medications used by persons aged 65 years or more. NSAIDs have a number of side effects, of which the most prevalent and serious is gastrointestinal (GI) toxicity. GI side effects of NSAIDs range from dyspepsia and gastroduodenal ulcers to serious, potentially fatal GI complications including bleeding and perforation. Serious GI complications often lack warning signs; knowledge of risk factors for NSAID-related gastropathy can identify patients at high risk, allowing for initiation of the appropriate therapeutic intervention. Risk factors include advanced age, NSAID dose, prior GI complications, infection with Helicobacter pylori, and use of corticosteroids and anticoagulants. There are few well-established strategies to prevent GI complications in NSAID users. Risk assessment and cotherapy with acid suppressors (H2-receptor antagonists and proton pump inhibitors) or prostaglandin replacement (misoprostol) and H pylori eradication are beneficial. Cyclooxygenase-1 (COX-1) is a key enzyme in gastroprotective mucosal defenses, and the best way to prevent GI toxicity is to avoid drugs that inhibit COX-1. Clinical studies of the COX-2-selective inhibitors rofecoxib and celecoxib have demonstrated efficacy equivalent to nonselective NSAIDs with lower rates of GI side effects (for example, incidence of endoscopic ulcers equivalent to placebo). Selective COX-2 inhibitors (coxibs) provide effective treatment of pain and inflammation while reducing risk of gastropathy.

Aspirin and proton pump inhibitor combination therapy for prevention of cardiovascular disease and Barrett's esophagus.

Aspirin, used at low doses (75-325 mg daily), prevents aggregation of platelets and is prescribed for patients as pharmacologic prevention of cardiovascular disease. Despite the well-documented beneficial effects of aspirin, prolonged use is associated with damage to the gastrointestinal (GI) mucosa in the upper and lower GI tract. Patient risk of hemorrhage and peptic ulcer formation is increased with older age, previous ulcer history, Helicobacter pylori infection, and concomitant use of nonsteroidal anti-inflammatory drugs, corticosteroids, or antithrombotic agents. As termination of aspirin therapy can precipitate a cardiovascular event, patients at risk need co-therapy with gastroprotective agents, such as proton pump inhibitors (PPIs), to reduce the GI side effects of aspirin treatment. Fixed-dose combinations of low-dose aspirin and gastroprotective agents have been designed to increase medication compliance, improve clinical outcomes, and reduce the overall cost of therapy. Prolonged use of PPIs may, however, lead to serious adverse effects or, in some cases, reduce the cardioprotective effects of aspirin. Hence, physicians need to carefully consider the benefits and risks associated with the condition of each patient to optimize clinical outcomes of combination therapy. A growing body of clinical evidence indicates that aspirin may decrease the risk of colorectal and other GI cancers, as well as reduce progression from Barrett's esophagus (BE) to esophageal adenocarcinoma. Furthermore, PPIs have recently been shown to reduce neoplastic transformation in patients with BE. Thus, the use of a fixed-dose aspirin/PPI combination could potentially provide chemopreventive benefit to patients with BE, and, at the same time, treat the underlying gastroesophageal reflux responsible for the condition.

Esomeprazole treatment of frequent heartburn: two randomized, double-blind, placebo-controlled trials.

PURPOSE: To determine the efficacy of a 14-day regimen of esomeprazole 20 mg for the treatment of frequent heartburn in subjects who are likely to self-treat with over-the-counter medications without consulting a health care provider. METHODS: Adults with frequent heartburn ≥ 2 days per week in the past 4 weeks were randomly assigned to 14-day double-blind treatment with esomeprazole 20 mg once daily or placebo in 2 identical multicenter studies (ClinicalTrials.gov identifiers: NCT01370525, NCT01370538). The primary efficacy outcome was percentage of heartburn-free 24-hour days across 14 days. Secondary efficacy outcomes included heartburn resolution, defined as heartburn ≤ 2 days over 14 days, and percentages of subjects reporting ≤ 1 day with heartburn in the first and final weeks of treatment. Subjects recorded data in daily self-assessment diaries. RESULTS: The percentage of heartburn-free 24-hour days over 14 days was significantly higher (P < 0.0001) in subjects receiving esomeprazole 20 mg compared with placebo in study 1 (N = 331; 46.13% vs. 33.07%, respectively) and study 2 (N = 320; 48.00% vs 32.75%, respectively). Significantly more subjects treated with esomeprazole 20 mg had heartburn resolution over 14 days and in the first and final weeks compared with placebo. Within the first 4 days, the proportion of subjects with heartburn-free days was significantly greater with esomeprazole 20 mg versus placebo. Treatment was generally well tolerated, with a safety pattern consistent with the known profile for esomeprazole. CONCLUSION: A 14-day regimen of esomeprazole 20 mg once daily was effective for treating frequent heartburn in subjects who are likely to self-treat with over-the-counter medications.

Pharmacodynamic evaluation of intragastric pH and implications for famotidine dosing in the prophylaxis of non-steroidal anti-inflammatory drug induced gastropathy-a proof of concept analysis.

OBJECTIVE: Famotidine given at a dose of 80 mg/day is effective in preventing NSAID-induced gastropathy. The aim of this proof of concept study was to compare twice a day (BID) vs 3-times a day (TID) administration of this total dose of famotidine on intragastric pH in healthy volunteers. RESEARCH DESIGN AND METHODS: Two analyses were undertaken: (1) a 13 subject controlled cross-over 24-h intragastric pH evaluation of the BID and TID administration of 80 mg/day of famotidine, as well as measures for drug accumulation over 5 days (EudraCT, number 2006-002930-39); and (2) a pharmacokinetic (PK)/pharmacodynamic (PD) model which predicted steady-state famotidine plasma concentrations and pH of the two regimens. RESULTS: For the cross-over study, gastric pH was above 3.5 for a mean of 20 min longer for TID dosing compared to BID dosing on Day 1. On Day 5, the mean time above this threshold was higher with the BID regimen by ∼25 min. For pH 4, subjects' gastric pH was above this pH value for a mean of 25 min longer for TID dosing compared to BID dosing on Day 1. For Day 5, the pH was above 4 for ∼45 min longer with the TID regimen as compared with the BID regimen. The mean 24-h gastric pH values when taken in the upright position trended higher for the TID dosing period compared to the BID regimen on Day 1. The steady-state simulation model indicated that, following TID dosing, intragastric pH will be above 3 for 24 h vs 16 h for the BID regimen. There was no evidence for plasma accumulation of famotidine with TID dosing as compared to BID dosing from either analysis. CONCLUSION: The data indicate that overall more time is spent above the acidic threshold pH values when 80 mg/day of famotidine is administered TID vs BID. Key limitations included small study size with a short duration and lack of a baseline examination, but was compensated for by the cross-over and PK/PD modeling design. Although most of the comparisons in this proof of concept study were not statistically significant these results have important implications for future research on gastric acid lowering agents used for the prevention of NSAID-induced gastropathy.

Budget impact modeling for a single-tablet formulation of ibuprofen and famotidine for prevention of upper gastrointestinal ulcers in patients with osteoarthritis and/or rheumatoid arthritis.

BACKGROUND: Single-tablet ibuprofen/famotidine is approved by the US Food and Drug Administration for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal (GI) ulcers in patients taking ibuprofen for those indications. Currently, little is known about the cost impact of gastroprotective therapies, and an estimate of the financial consequences of adopting these therapies will be helpful to decision makers. OBJECTIVES: The goal of this study was to review a model that evaluates the expected financial impact to US health care plans from the introduction of single-tablet ibuprofen/famotidine into the chronic NSAID user population. METHODS: A budget impact model, considering a typical health plan of 1 million enrollees, was used to compare patients receiving: (1) single-tablet ibuprofen/famotidine; (2) chronic NSAID treatment plus any GI-protective agent; and (3) chronic NSAID treatment without a GI-protective agent. RESULTS: The expected medication cost for single-tablet ibuprofen/famotidine was $734,192 ($81,577 in year 1, $244,731 in year 2, and $407,884 in year 3), corresponding to a total per-member per-month cost of $0.020 ($0.007 in year 1, $0.020 in year 2, and $0.034 in year 3). Considering anticipated decreases in the use of other NSAIDs, the use of GI-protective agents, and GI complications, the total expected 3-year drug cost for single-tablet ibuprofen/famotidine was offset by 50%, representing an estimated total budget impact of $364,396 or $0.010 per member per month. Sensitivity analyses of cost and market share variables and clinical and drug characteristics identified the most influential variables to be the cost of the drug and persistence to the ibuprofen/famotidine formulation, respectively. CONCLUSIONS: The expected decrease in treatment costs for less serious GI-related complications illustrates the benefits of single-tablet ibuprofen/famotidine as a gastroprotective therapy in patients receiving chronic NSAID treatment, with a modest financial impact on total health care costs.