s-1743 and Gastrointestinal-Hemorrhage

Aspirin and P2Y

Topics: Adenosine; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Administration Schedule; Drug Dosage Calculations; Drug Interactions; Esomeprazole; Gastrointestinal Hemorrhage; Gene Expression; Humans; Hydrogen-Ion Concentration; Peptic Ulcer; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Dose-Response Relationship, Drug; Esomeprazole; Gastrointestinal Hemorrhage; Global Health; Humans; Incidence; Peptic Ulcer; Proton Pump Inhibitors; Risk Assessment

The drug interaction between proton pump inhibitors and clopidogrel has been the subject of much study in recent years. Contradictory results regarding the effect of proton pump inhibitors on platelet reactivity and on clinical outcome in clopidogrel-treated patients have been reported in literature. Concomitant use of omeprazole and clopidogrel was found to decrease the exposure (AUC) to clopidogrel's active metabolite by 50% and to sharply increase platelet reactivity, as a result of inhibition by omeprazole of CYP2C19, a cytochrome P450 (CYP) enzyme. Pantoprazole has a much weaker effect on clopidogrel's pharmacokinetics and on platelet reactivity during concomitant use. The influence of the other proton pump inhibitors when used simultaneously with clopidogrel has not yet been investigated in adequately randomized studies. Regulatory agencies state that the combination of clopidogrel and the CYP2C19 inhibitors omeprazole and esomeprazole should be avoided. To date, there is no conclusive evidence of a clinically-relevant interaction between any of the proton pump inhibitors and clopidogrel.

Topics: Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 Enzyme System; Drug Interactions; Drug Therapy, Combination; Esomeprazole; Gastrointestinal Hemorrhage; Humans; Omeprazole; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Ticlopidine

A large number of patients require antiplatelet therapy (mainly aspirin and/or clopidogrel). Recent studies suggest that the combination of these agents is useful in patients with acute coronary syndrome and after percutaneous coronary intervention with stent placement. On the other hand, bleeding complications, most of which arise from the upper gastrointestinal (UGI) tract, can limit the use of antiplatelet drugs. Clopidogrel appears to be associated with fewer UGI side effects and bleeding compared with aspirin. However, a history of previous UGI bleeding is a major risk factor for clopidogrel-associated bleeding. The use of proton-pump inhibitors (PPIs) decreases the rate of UGI bleeding in patients receiving aspirin or clopidogrel. Furthermore, a recent study suggested that the administration of low-dose aspirin plus high-dose esomeprazole (a potent PPI) was associated with fewer episodes of UGI bleeding than clopidogrel alone in patients with a history of recent UGI haemorrhage. However, this study had several limitations and its results should be cautiously extrapolated into clinical practice. The combination of aspirin plus clopidogrel increases the risk of UGI bleeding. Unfortunately, there are no data on the effect of PPI prophylaxis in this setting. Available evidence suggests that where aspirin and/or clopidogrel are to be started or continued in patients with a recent history of UGI ulceration or bleeding (after ulcer healing and eradication of H. pylori infection), treatment with a PPI is a useful precaution. The patients should also be carefully monitored for recurrence of UGI bleeding.

Topics: Aspirin; Clopidogrel; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Esomeprazole; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Risk Factors; Ticlopidine

Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users.. Thirty-two recruited patients, who received LDA (100 mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20 mg/day) and 17 patients additionally receiving vonoprazan (10 mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured.. Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p < 0.0001) than in the esomeprazole group (p = 0.0024). The Lactobacillales proportion was positively correlated with the gastrin level (r = 0.5354). No significant hemoglobin or hematocrit level reduction was observed in subjects receiving LDA with additional PPI.. Additional PPI administration increased the Lactobacillales proportion in the microbiota of LDA users. The positive correlation between the gastrin level and the proportion of Lactobacillales suggested that the change in the intestinal flora was associated with the degree of suppression of gastric acid secretion. Additional oral PPI did not significantly promote anemia, but the risk of causing PPI-induced small-intestinal mucosal injury in LDA users should be considered.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Case-Control Studies; Comorbidity; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastrins; Gastrointestinal Hemorrhage; Gastrointestinal Microbiome; Hematocrit; Hemoglobins; Humans; Intestinal Mucosa; Lactobacillales; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Sulfonamides

To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator.. A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique.. Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive "coffee grounds" material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients.. Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control.. ClinicalTrials.gov identifier NCT02157376.

Topics: Adult; Aged; Cimetidine; Critical Illness; Double-Blind Method; Esomeprazole; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged

To investigate the optimum period of treatment for post endoscopic submucosal dissection (ESD) ulcers.. Patients who underwent ESD for gastric cancer were randomized to two groups and treated with esomeprazole 20 mg per day for 4 wk (4W group) or 2 wk (2W group). At 4 wk after ESD, we measured the size of the artificial ulcers by endoscopy and determined the ulcer healing rate, compared with the size of the ESD specimens. This randomized controlled trial study was approved by our ethics committee and registered in the UMIN Clinical Trial Registry.. A total of 60 consecutive patients were included in the study. All patients received rebamipide 300 mg per day for 4 wk. One patient in 2W group who showed bleeding within two weeks and received endoscopic treatment was excluded from further analysis. The numbers of patients with ulcers in the healing/scar stage in the 2W and 4W groups at 4 wk after ESD were 20/6 and 28/5, respectively, with no significant difference. The ulcer healing rate in the 2W and 4W groups were 96.1% [95% confidence interval (CI): 94.6%-97.55] vs 94.8% (95%CI: 92.6%-97.1%), respectively, with no statistical difference (UMIN000006951).. Two-wk treatment with a proton pump inhibitor is as effective as four-week treatment for healing post ESD ulcers.

Topics: Aged; Aged, 80 and over; Dissection; Drug Administration Schedule; Esomeprazole; Female; Gastrectomy; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Japan; Male; Middle Aged; Proton Pump Inhibitors; Stomach Neoplasms; Time Factors; Treatment Outcome; Ulcer; Wound Healing

Little is known about the efficacy of proton pump inhibitors compared with H(2) receptor antagonists in preventing adverse upper gastrointestinal complications in patients with acute coronary syndrome (ACS) or ST elevation myocardial infarction (STEMI) receiving aspirin, clopidogrel, and enoxaparin or thrombolytics. The objective of this study was to compare the efficacies of esomeprazole and famotidine in preventing gastrointestinal complications.. A double-blind, randomized, controlled trial was performed in patients receiving a combination of aspirin, clopidogrel, and either enoxaparin or thrombolytics. Patients received either esomeprazole (20 mg nocte) or famotidine (40 mg nocte) orally for 4-52 weeks, depending on the duration of dual antiplatelet therapy. The primary end point was upper gastrointestinal bleeding (GIB), perforation, or obstruction from ulcer/erosion (http://www.clinicaltrials.gov NCT00683111).. In all, 311 patients were recruited, with 163 and 148 patients in the esomeprazole and famotidine groups, respectively. Mean (s.d.) follow-up was 19.2 (17.6) and 17.6 (18.0) weeks, respectively. One (0.6%) patient in the esomeprazole group and 9 (6.1%) in the famotidine group reached the primary end point (log-rank test, P=0.0052, hazard ratio=0.095, 95% confidence interval: 0.005-0.504); all had upper GIB.. In patients with ACS or STEMI, esomeprazole is superior to famotidine in preventing upper gastrointestinal complications related to aspirin, clopidogrel, and enoxaparin or thrombolytics.

Topics: Acute Coronary Syndrome; Aged; Anti-Ulcer Agents; Aspirin; Chi-Square Distribution; Clopidogrel; Double-Blind Method; Drug Therapy, Combination; Enoxaparin; Esomeprazole; Famotidine; Female; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Intestinal Perforation; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Ticlopidine; Treatment Outcome

Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events.Methods and Results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole.. Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Topics: Aged; Aspirin; Cardiovascular Diseases; Cost-Benefit Analysis; Esomeprazole; Gastrointestinal Hemorrhage; Humans; Japan; Lansoprazole; Proton Pump Inhibitors; Pyrroles; Secondary Prevention

Proton pump inhibitors are potent suppressors of gastric acid secretion, and are commonly prescribed in palliative medicine. Despite multiple relevant indications in patients at the end-of-life, their use is often precluded as oral and intravenous administration is frequently inappropriate or not possible. Limited anecdotal evidence suggests proton pump inhibitors may be administered subcutaneously. Our objective was to investigate the tolerability and effectiveness of the administration of esomeprazole as a continuous subcutaneous infusion over 24 h via a syringe driver.. Case series (n = 7) design assessing sequential patients admitted to a specialist inpatient centre for palliative care, who required parenteral proton pump inhibitor therapy.. Four patients reported complete resolution of dyspeptic and reflux symptoms post commencement of esomeprazole. Two patients developed upper gastrointestinal bleeding, which via observation of vomitus and stools, resolved with the initiation of esomeprazole. A single patient, deemed high risk of gastrointestinal bleeding, was commenced on esomeprazole and no bleeding events occurred.. Esomeprazole when administered via a syringe driver over 24 h appears well tolerated and effective for the symptomatic management of dyspepsia and treatment of gastrointestinal bleeding. Overall, this series adds to the limited evidence base for using subcutaneous proton pump inhibitors in the palliative demographic.

Topics: Demography; Esomeprazole; Gastrointestinal Hemorrhage; Humans; Palliative Care; Proton Pump Inhibitors; Syringes; Treatment Outcome

Critically ill patients admitted to intensive care units (ICUs) are at high risk of developing upper gastrointestinal bleeding due to GI stress ulceration (SU). The major independent risk factors for the development of GI bleeding in the ICUs include mechanical ventilation (MV) and coagulopathy. There is no enough evidence regarding the most appropriate dosing of esomeprazole as stress ulcer prophylaxis (SUP) in critically ill patients. This is a retrospective cohort study conducted at King Abdulaziz Medical City-Riyadh between January and December 2018 to determine the efficacy and safety of two different regimens of esomeprazole (20 vs 40 mg) as SUP in critically ill patients with major risk factors of GI stress ulceration. A total of 1864 patients were reviewed, 387 patients meeting inclusion criteria were enrolled. The propensity score was used to adjust for clinically and statistically relevant variables. We considered a P value of <.05 as statistically significant. 49 patients (12.6%) had received Esomeprazole 20 mg during the study period. Compared with Esomeprazole 20 mg, Esomeprazole 40 mg was not superior in GI bleeding prevention (aOR 2.611, 95% CI 0.343-20.247, P = .356). In addition, neither ICU C. difficle, ICU mortality within 30 days, ICU LOS, hospital LOS, ICU re-admission within 6 months, RBCs transfusion, nor platelets transfusion requirements were significant. On the other hand, Esomeprazole 40 mg was statistically associated with Enterobacteriaceae, Pneumonia, and longer MV duration.

Topics: Adult; Aged; Aged, 80 and over; Anti-Ulcer Agents; Cohort Studies; Critical Illness; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastrointestinal Hemorrhage; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Peptic Ulcer; Proton Pump Inhibitors; Retrospective Studies; Risk Factors

Topics: Cimetidine; Critical Illness; Double-Blind Method; Esomeprazole; Gastrointestinal Hemorrhage; Histamine; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors; Protons

Topics: Aged, 80 and over; Anti-Bacterial Agents; Blood Transfusion; Colitis; Colon; Cytomegalovirus; Cytomegalovirus Infections; Diarrhea; Esomeprazole; Gastrointestinal Hemorrhage; Gastrointestinal Tract; Humans; Immunocompetence; Male; Penicillanic Acid; Piperacillin; Pneumonia; Pulmonary Disease, Chronic Obstructive; Steroids; Tazobactam; Treatment Outcome; Viremia

Proton pump inhibitors (PPIs) are commonly overused in hospitalized patients. The objectives of this study were to determine the extent of their inappropriate initiation in patients with low risk for gastrointestinal hemorrhage, factors associated with their continuation on discharge and potential cost of this trend.. Retrospective examination of patients with low risk for gastrointestinal hemorrhage admitted to a tertiary-care teaching hospital over a 3-month period who received esomeprazole. The following information was collected: age, gender, PPI status (de novo or continued) and admitting diagnoses. Additional information collected from the de novo subgroup included indication for PPI, number of days on PPI and continuation of the drug on discharge. The cost of the medication was obtained from pharmacy records.. Four hundred nine patients were admitted during the study period and 204 (49.9%) received PPI de novo. Among these, 155 patients (76%) had an inappropriate indication for PPI. Of these, 62 (40%) patients were continued on PPI on discharge. Older age was a significant predictor of continuation of PPI at discharge. The estimated cost of the inpatient and outpatient inappropriate use of PPI was $12,272 and $59,272, respectively.. PPIs are overused in the majority of hospitalized patients with low risk for gastrointestinal bleeding and this practice gets perpetuated at discharge, especially in older patients. The cost of this phenomenon is alarming.

Topics: Aged; Aged, 80 and over; Esomeprazole; Female; Gastrointestinal Hemorrhage; Hospitalization; Humans; Inappropriate Prescribing; Male; Middle Aged; Proton Pump Inhibitors; Retrospective Studies

The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain.. To compare the treatment effects of continuous infusion and low-dose esomeprazole therapies in patients with non-variceal upper gastrointestinal (GI) bleeding.. This prospective clinical study compared continuous infusion of esomeprazole (80 mg bolus followed by 8 mg∕h continuous infusion for 72 h) and low-dose esomeprazole (40 mg twice daily IV) treatments in GI bleeding patients with peptic ulcer presenting a high risk of re-bleeding, who were administered a successful endoscopic homeostasis. The primary end point was the occurrence of re-bleeding during hospitalization and within one month of discharge. Secondary outcomes were defined as duration of hospitalization, need of transfusion, surgical treatment, and mortality rate. After 72 h, both groups were switched to oral esomeprazole therapy for one-month.. A hundred thirty-two subjects were enrolled. Re-bleeding occurred in 11 (16.7%) patients in the infusion therapy group and in 12 (18.2%) patients in the low-dose group (P=0.819) within the first 72 h. No patient experienced re-bleeding in the first month following discharge. There was no statistical significant difference between the two groups in terms of transfusion need, durations of hospitalization, need for surgery and mortality rate.. PPI infusion therapy following endoscopic hemostasis treatment was not found superior to low-dose PPI therapy in the terms of re-bleeding, need of surgery and mortality.

Topics: Aged; Blood Transfusion; Dose-Response Relationship, Drug; Esomeprazole; Female; Gastrointestinal Hemorrhage; Hemostasis, Endoscopic; Hospitalization; Humans; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Peptic Ulcer; Prospective Studies; Proton Pump Inhibitors; Recurrence; Upper Gastrointestinal Tract; Vascular Surgical Procedures

It is common practice to replace aspirin with clopidogrel in patients with gastrointestinal intolerance to aspirin. Recent studies suggest that a combination of aspirin and a proton pump inhibitor is a better alternative for these patients. The CAPRIE and CURE studies have not shown any clinically relevant difference in effect between aspirin and clopidogrel. The incidence of bleeding is also similar when aspirin is used in doses < 160 mg. A recent study by Chan et al. concluded that a combination of aspirin and esomeprazole is superior to clopidogrel in the prevention of recurrent gastrointestinal bleeding. Using aspirin and a proton pump inhibitor is also the least expensive alternative.

Topics: Anti-Ulcer Agents; Aspirin; Clopidogrel; Cost-Benefit Analysis; Drug Costs; Drug Therapy, Combination; Esomeprazole; Evidence-Based Medicine; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Ticlopidine