Upper Gastrointestinal Bleeding Events Research Articles

Nonvitamin K oral anticoagulants with proton pump inhibitor cotherapy ameliorated the risk of upper gastrointestinal bleeding

Proton pump inhibitors (PPIs) can reduce the risk of upper gastrointestinal bleeding (UGIB) in patients who are taking oral anticoagulants. This study aimed to identify the association between NOACs with PPI cotherapy and UGIB. This retrospective cohort analysis included patients over the age of 18 years who were using NOACs between 2013 and 2020. NOAC categories, concomitant medications, endoscopic findings, the HAS-BLED score and the Charlson Comorbidity Index score were recorded. Using Poisson regression models, the relationship between UGIB events and risk factors was analyzed. Throughout a mean follow-up of 29.5 months, 14 (5.1%) individuals experienced UGIB. The incidence of UGIB was greater in patients receiving NOACs without PPIs (2.7 [1.26–5.60] per 1000) than in those receiving NOACs with PPIs (1.3 [0.61–2.67] per 1000). Patients receiving NOACs with PPIs had a 79.2% lower incidence of UGIB than patients receiving NOAC monotherapy (RR 0.208, 95% CI 0.061–0.706; p = 0.012). Female sex and the HAS-BLED score were associated with UGIB (RR 5.043; 95% CI 1.096–23.20; p = 0.038; RR 2.024; 95% CI 1.095–3.743; p = 0.024, respectively). Patients receiving NOAC and PPI cotherapy had a lower incidence of UGIB than those receiving NOACs alone, and female sex was a risk factor for UGIB in NOAC-treated patients.

Concomitant oral potassium chloride and anticholinergic therapy is associated with upper gastrointestinal bleeding: A cohort study.

To determine whether oral potassium chloride (KCI) therapy with concomitant anticholinergic exposure among hospitalized patients is associated with an excess risk for upper gastrointestinal bleeding (UGIB). A retrospective controlled study among hospitalized patients between January 2007 and April 2019 who were treated with oral KCI. Patients were divided into two groups: with or without concomitant exposure to agents with anticholinergic activity. Outcome was defined as any UGIB. The final sample included 13 728 subjects who received oral KCI treatment, of them 3542 (25.8%) had at least one documented overlap with an anticholinergic agent. Mean age was 67.6 (±17.2) and 6893 (50.2%) were females. Median KCI dose was 2.4 g (interquartile range [IQR] 1.2-5.4, n = 9416) with the majority (90.4%) being treated with the wax-matrix form (Slow-K). Twenty-six (0.2%) patients experienced an UGIB event. Univariate analysis demonstrated a significantly higher rate of UGIB among patients concomitantly treated with oral KCI and anticholinergics (0.3%) compared to those without anticholinergic exposure (0.1%, P = 0.018), with median 7 days (IQR 3-16.8) from first KCI dose to bleeding event. Multivariate analysis demonstrated that concomitant anticholinergic exposure (Odds Ratio 2.48, 95% Confidence Interval 1.11-6.51, P = 0.022) and anticoagulation treatment among patients with hemato-oncologic disease (OR 6.61, 95% CI 1.96-22.25, P = 0.002) were significantly associated with UGIB. Hospitalized patients treated concomitantly with oral KCI and anticholinergic agents have significantly increased risk for UGIB.

Endoscopic Utilization and Outcomes of Upper Gastrointestinal Bleeding in COVID-19: A Global Real-World Database Analysis

Introduction: Upper gastrointestinal bleeding (UGIB) events are increasingly recognized in the Coronavirus Disease-2019 (COVID-19) patients. The data about the rates of utilization of endoscopy and outcomes among these patients are scarce.Methods: All hospitalized COVID-19 patients with UGIB (hematemesis or melena or both) were studied from January 1, 2020, to September 1, 2020, from the TriNetX multicenter research network database. Patients were divided into two groups- patients who underwent any endoscopies (endoscopy group) and did not undergo endoscopy (non-endoscopy group). A subgroup analysis was performed for patients with variceal (V-UGIB) and non-variceal UGIB (NV-UGIB). Mortality and development of acute respiratory distress syndrome were the primary outcomes of the study. Secondary outcomes were cross-section imaging (CT scan of the abdomen) and mechanical ventilation.Results: A total of 3466 hospitalized COVID-19 had UGIB events from January 1, 2020, to September 1, 2020. 3.1% (3466/112,158). Only 51.1% of patients (1773/3446) underwent an endoscopy. The endoscopy group had a lower risk of mortality (risk ratio [RR] 0.63, 95%CI:0.52–0.77), and ARDS (RR 0.39, 95%CI:0.22–0.71). Rates of mechanical ventilation (RR 0.66, 95%CI:0.47–0.91) were lower, and the rate of CT scan utilization (RR 1.20, 95%CI:1.01–1.42) were higher in the endoscopy group. No differences in the outcomes were noted in V-UGIB and NV-UGIB groups.Conclusion: UGIB events in hospitalized adult COVID-19 patients was 3.1%. Endoscopy utilization in this cohort was associated with a significantly lower risk of mortality (37%) and ARDS (61%). Future prospective studies are needed to validate these findings.Funding Statement: None.Declaration of Interests: The authors have no commercial associations or sources of support that might pose a conflict of interest.Ethics Approval Statement: TriNetX has received a waiver from IRB since it does not contain any protected health information (PHI) or the HCO Information, and only includes aggregated counts and statistical summaries of de-identified information.

Decline in acute upper gastrointestinal bleeding during COVID-19 pandemic after initiation of lockdown in Austria.

Background COVID-19 has spread rapidly around the world. The Austrian government implemented a lockdown on 16 March to contain further spread of the disease. We investigated the effects of lockdown on acute upper gastrointestinal (GI) bleeding in Austria. Methods We contacted 98 Austrian hospitals performing emergency endoscopies. The hospitals were asked to report upper GI endoscopies performed for recent hematemesis, melena, or both, and exhibiting endoscopically visible signs of bleeding. The study period was from 3 weeks before (calendar Week 9) to 3 weeks after (Week 14) initiation of the lockdown. Results 61 % of Austrian hospitals, and importantly all major state hospitals, responded. A total of 575 upper GI bleedings occurred during the 3 weeks before and 341 during the 3 weeks after initiation of lockdown (40.7 % reduction). There was a 54.6 % decline in nonvariceal bleeding events at Week 14 compared with Week 9 (89 vs. 196), whereas rates of variceal hemorrhage did not change (15 vs. 17). Conclusions National lockdown resulted in a dramatic decrease in upper GI bleeding events in Austrian hospitals.

Upper gastrointestinal bleeding in Japanese patients with ischemic heart disease receiving vonoprazan or a proton pump inhibitor with multiple antithrombotic agents: A nationwide database study

BackgroundVonoprazan has been launched as an alternative to proton-pump inhibitors (PPIs). This was the first study to compare the occurrence of upper gastrointestinal bleeding (UGIB) with vonoprazan treatment to that with PPI treatment in patients with ischemic heart disease (IHD) taking ≥2 antithrombotic agents, including those receiving dual antiplatelet therapy (DAPT). MethodsUsing Japanese Diagnosis Procedure Combination data from 2016 to 2017, we identified 16,415 patients with IHD who were prescribed ≥2 antithrombotic agents, including new antiplatelet medication with concurrent vonoprazan (n = 2226 or PPIs n = 14,189). UGIB occurrence was analyzed using an inverse probability-weighted Cox proportional hazards model. Non-inferiority of vonoprazan to PPI treatment for UGIB occurrence was assessed. ResultsSix-month incidence of UGIB in patients treated with vonoprazan and PPIs was 3.14% 70/2226 and 4.17% (591/14,189), respectively. The adjusted hazard ratio (aHR) of 0.84 was significantly below the non-inferiority margin (HR 2.06) (p < 0.0001), and thus demonstrated that vonoprazan treatment was non-inferior to PPIs in terms of occurrence of UGIB events. The difference between the 2 treatments was also not statistically significant [aHR 0.84; 95% confidence interval (CI): 0.65–1.07; p = 0.154). In a subgroup analysis, UGIB occurrence with vonoprazan and other PPI treatment in patients receiving DAPT was 2.82% (22/779) and 3.96% (209/5276) respectively; a non-significant difference (aHR 0.74; 95% CI: 0.48–1.16; p = 0.189) that demonstrated non-inferiority (p < 0.0001). ConclusionsVonoprazan was non-inferior to PPIs in terms of UGIB occurrence over 6 months in patients with IHD receiving ≥2 antithrombotic agents, including new antiplatelet medication.

Gastrointestinal Bleeding After HeartMate II or HVAD Implantation: Incidence, Location, Etiology, and Effect on Survival.

The number of patients on destination therapy is increasing as long-term survival on continuous-flow left ventricular assist device (CF-LVAD) therapy has improved. Gastrointestinal bleeding (GIB) is a common complication after CF-LVAD implantation, and its risk correlates with longer support time, emphasizing the importance of GIB management. The lower pulsatility of CF-LVADs may promote arteriovenous malformations, which amplify the bleeding risk. Here, we retrospectively analyzed the location, incidence, and survival effect of GIB events in HeartMate II (HM-II) and HeartWare Ventricular Assist Device (HVAD) recipients to provide specific details regarding these complications. From November 2003 to March 2016, 526 patients with chronic heart failure underwent primary implantation of an HM-II (n = 403) or HVAD (n = 123) CF-LVAD at our center. Of the 526 patients, 140 (26.6%) had a GIB event (HM-II: n = 100; HVAD: n = 40), 92 (17.5%) had a single GIB event, and 48 (9.1%) had multiple GIB events (range: 2-9 events). HVAD recipients had a higher incidence of both upper and lower GIB events (p < 0.001 and P = 0.002, respectively) than HM-II recipients. Arteriovenous malformation was the most common etiology for GIB (50 patients/72 events); for this group, the average time-to-event was 300.4 days, the recurrence rate was 34%, and the 90-day and 1-year survival rates were 88.3% and 66.7%, respectively. Age at implantation was the only predictor of GIB. In conclusion, our study provides detailed information about GIB events associated with current CF-LVADs. Additional studies are required to evaluate strategies to reduce the incidence of GIB morbidity.

High risk of gastrointestinal hemorrhage in patients with systemic sclerosis

BackgroundSystemic sclerosis (SSc), a life-threatening autoimmune disease characterized by vasculopathy. Numerous SSc patients demonstrate gastrointestinal (GI) involvement but the delicate GI bleeding risk remains sparse. We aimed to explore the role of SSc in determining the long-term risk of GI bleeding, including bleedings of upper (peptic and non-peptic ulcers) and lower GI tracts.MethodsPatients with SSc diagnosis were identified from the Catastrophic Illness Patient Database and the National Health Insurance Research Database from 1998 to 2007. Each SSc patient was matched with five SSc-free individuals by age, sex, and index date. All individuals (case = 3665, control = 18,325) were followed until the appearance of a GI bleeding event, death, or end of 2008. A subdistribution hazards model was assessed to evaluate the GI bleeding risk with adjustments for age, sex, and time-dependent covariates, comorbidity, and medications.ResultsThe incidence rate ratios of GI bleeding were 2.38 (95% confidence interval [CI], 2.02–2.79), 2.06 (95% CI, 1.68–2.53), and 3.16 (95% CI, 2.53–3.96) for over-all, upper, and lower GI bleeding events in SSc patients. In the competing death risk in the subdistribution hazards model with time-covariate adjustment, SSc was an independent risk factor for over-all GI bleeding events (subdistribution hazard ratio [sHR] 2.98, 95% CI, 2.21–4.02), upper GI bleeding events (sHR 2.80, 95% CI, 1.92–4.08), and lower GI bleeding events (sHR 3.93, 95% CI, 2.52–6.13).ConclusionSSc patients exhibited a significantly higher risk of over-all and different subtype GI bleeding events compared with the SSc-free population. The prevention strategy is needed for these high GI bleeding risk groups.

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial

SummaryBackgroundThe omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy.MethodsIn a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55–73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847.FindingsBetween Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference −0·9%, −8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference −0·6%, −8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group).InterpretationNeither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence.FundingEfficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.

Non-steroidal anti-inflammatory drug related upper gastrointestinal bleeding: types of drug use and patient profiles in real clinical practice

Background: The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied.Objectives and methods: To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case–control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0.Results: Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (<30 days) of NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32–5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms.Conclusions: The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention strategies may not reach a wide population of short-term NSAID users.

Proton-pump inhibitors for prevention of upper gastrointestinal bleeding in patients undergoing dialysis.

To investigate the preventive effects of low-dose proton-pump inhibitors (PPIs) for upper gastrointestinal bleeding (UGIB) in end-stage renal disease. This was a retrospective cohort study that reviewed 544 patients with end-stage renal disease who started dialysis at our center between 2005 and 2013. We examined the incidence of UGIB in 175 patients treated with low-dose PPIs and 369 patients not treated with PPIs (control group). During the study period, 41 patients developed UGIB, a rate of 14.4/1000 person-years. The mean time between the start of dialysis and UGIB events was 26.3 ± 29.6 mo. Bleeding occurred in only two patients in the PPI group (2.5/1000 person-years) and in 39 patients in the control group (19.2/1000 person-years). Kaplan-Meier analysis of cumulative non-bleeding survival showed that the probability of UGIB was significantly lower in the PPI group than in the control group (log-rank test, P < 0.001). Univariate analysis showed that coronary artery disease, PPI use, anti-coagulation, and anti-platelet therapy were associated with UGIB. After adjustments for the potential factors influencing risk of UGIB, PPI use was shown to be significantly beneficial in reducing UGIB compared to the control group (HR = 13.7, 95%CI: 1.8-101.6; P = 0.011). The use of low-dose PPIs in patients with end-stage renal disease is associated with a low frequency of UGIB.

Patterns in the use of low-dose acetylsalicylic acid and other therapies following upper gastrointestinal bleeding.

Anticoagulants and/or antiplatelet agents such as acetylsalicylic acid (ASA) are important in prevention of cardiovascular (CV) events, but may be associated with upper gastrointestinal bleeding (UGIB). However, discontinuing these agents may leave patients at risk of CV events. This study aimed to assess patterns of therapy after UGIB in routine clinical practice. The Health Improvement Network UK primary care database was used to identify a cohort of patients aged 40-84 years with a UGIB event between 2000 and 2007 (n = 2,036). Patients were followed up for 1 year from the recorded UGIB. Re-prescription rates for antithrombotics and drugs that can modify the risk of UGIB were estimated at 30, 90, 180, and 365 days. At 365 days, the re-prescription rate was 43 % for ASA, 66 % for warfarin, 69 % for clopidogrel, and 49 % for dipyridamole. The re-prescription rate of gastroprotective agents at 365 days for current users of histamine H2-receptor antagonists was 36 % and that of proton pump inhibitors (PPIs) was 97 %. In patients who were prescribed ASA before UGIB (n = 572), only 24 % were prescribed a PPI in the previous year. In patients who were prescribed ASA in the year after UGIB (n = 337), 92 % were prescribed a PPI. Antiplatelet use fell after UGIB events. In patients who were prescribed a PPI after a UGIB event, there was increased re-prescription of antiplatelet agents and antithrombotics.

Cardiovascular and upper gastrointestinal bleeding consequences of low-dose acetylsalicylic acid discontinuation

It was the aim of this study to investigate whether low-dose acetylsalicylic acid (ASA) therapy for secondary cardiovascular prevention should continue, despite the risk of gastrointestinal bleeding. We aimed to make a clinically meaningful benefit-risk assessment regarding the cardiovascular and gastrointestinal consequences of ASA discontinuation.This case-control study usedThe Health Improvement Network UK primary care database to identify patients aged 50-84 years during 2000-2007 with a first ASA prescription for secondary cardiovascular prevention (N = 39,513). New cases of non-fatal myocardial infarction (MI)/coronary death (n=1,222), ischaemic stroke (IS)/transient ischaemic attack (TIA) (n= 673) and upper gastrointestinal bleeding (UGIB) (n = 169) were identified after a mean follow-up of 3.2, 3.4 and 4.0 years, respectively. ASA discontinuers before the index date were identified. Attributable risks associated with ASA discontinuation were calculated and National Institute for Health and Clinical Excellence annual economic data were used to estimate healthcare costs. The cumulative incidences of non-fatal MI/coronary death, IS/TIA and UGIB among ASA discontinuers within the first year of follow-up were 17, 11 and 1.6 per 1,000 persons, respectively. This corresponds to eight extra cardiovascular events, and a reduction of 0.4 UGIB events per year compared with current ASA users. Extrapolating to the UK population aged over 50 years, avoiding discontinuation of ASA could prevent 12,786 coronary and 7,672 cerebrovascular events/year, at the expense of 1023 extra UGIB events, saving approximately £100 million/year. In conclusion, preventing patients with cardiovascular disease from discontinuing ASA could result in substantial clinical and economic gains.

Antidepressant Use and the Risk of Upper Gastrointestinal Bleeding in Psychiatric Patients

The magnitude of risk between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding (UGIB) is still unknown in patients with psychiatric diseases. The aim of this study was to quantify the risk of UGIB induced by use of antidepressants with different affinities for serotonin transporters in psychiatric patients using Taiwan's nationwide health insurance claims database. We conducted a propensity score- matched retrospective cohort study and identified 304,606 psychiatric patients who initiated antidepressant treatment during the 2005-2006 period. Antidepressants were classified as high- (HA group), intermediate- (IA group), or low-affinity (LA group) serotonin reuptake inhibitors. Patients in the LA group were matched 1:1 to those in the HA and IA groups according to their propensity scores. Subjects who were successfully matched were followed up from the date of antidepressant initiation to first hospitalization for UGIB, drug discontinuation, transition to or addition of antidepressants in another group, or the study's end (whichever occurred first). A total of 153,486 psychiatric patients were successfully matched, and 498 first UGIB events were identified. Compared with the LA group, patients in the HA group had a higher risk for UGIB (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.11-1.71). The HR (95% CI) of the IA group was 1.11 (95% CI, 0.88-1.41). The trend for elevated UGIB risk with increasing affinity of serotonin transporters was statistically significant (P < 0.01). Elderly patients and those with prior UGIB history were more susceptible to the harmful effects. Our findings suggest that the use of high-affinity serotonin reuptake inhibitors may increase the risk for UGIB in psychiatric patients.

Prediction and prevention of upper gastrointestinal bleeding after cardiac surgery: a case control study.

Gastrointestinal (GI) complications of cardiovascular surgery, particularly bleeding, occur frequently. To determine factors that predict upper GI bleeding (UGIB) after cardiac surgery to improve prognostication and, thus, outcomes. The present case-control study reviewed institutional records spanning 2002 to 2005 for consecutive patients who developed in-hospital UGIB following cardiovascular surgery. Each case was matched to two to three controls for age, sex and date of hospital admission. Demographics, pharmacotherapy (including use of in-hospital acid suppression), endoscopic findings and outcomes were recorded. After adjustment for possible confounders, including Parsonnet score and demographic parameters, conditional logistic regression analysis identified independent significant predictors of the subsequent development of UGIB. The study population consisted of 131 cases (mean [± SD] age 68.8±10.2 years, 69.5% male, mean Parsonnet score 24.6±14.2) and 387 matched controls (mean age 68.8±10.8 years, 70.0% male, mean Parsonnet score 20.9±14.2). UGIB events occurred a mean of 10.3±7.7 days after cardiac surgery. Duration of mechanical ventilation (OR 3.01 [95% CI 1.44 to 6.28]), elevation of international normalized ratio (OR 1.91 [95% CI 1.31 to 2.78]) and occurrence of Clostridium difficile colitis before bleeding (OR 3.15 [95% CI 1.19 to 8.36]) were independent risk factors. Use of histamine type 2 receptor antagonists (H2RAs) (OR 0.65 [95% CI 0.38 to 1.12]) or proton pump inhibitors (PPIs) (OR 0.60 [95% CI 0.27 to 1.32]) demonstrated trends toward protecting against UGIB after cardiac surgery. GI bleeding events occurred approximately 10 days after cardiac surgery in patients with a complicated postoperative course. Significant predictors of subsequent bleeding included increased duration of mechanical ventilation and elevation of international normalized ratio; routine acid suppression with PPIs should be considered in such patients. C difficile colitis also significantly predicted UGIB, and H2RAs should be considered for acid suppression. Neither H2RAs nor PPIs were effective in preventing UGIB, although the small number of patients limits definitive conclusions regarding the role of acid suppression.

Cost-effectiveness analysis: cardiovascular benefits of proton pump inhibitor co-therapy in patients using aspirin for secondary prevention

Many patients with cardiovascular (CV) disease will stop aspirin (ASA) because of ASA-related dyspepsia. Proton pump inhibitor (PPI) co-therapy may reduce ASA-related dyspepsia, enhancing ASA adherence and improving CV outcomes. To explore the impact of PPI co-therapy on CV outcomes in long-term, low-dose ASA users. We modified a previously published Markov model to assess the long-term impact of PPI co-therapy on CV and upper gastrointestinal bleeding (UGIB) outcomes among patients using ASA for secondary CV prevention. UGIB events, recurrent myocardial infarctions (MIs) and incremental cost-effectiveness ratios (ICERs) were measured. The perspective taken was that of a long-term payer. Compared with ASA alone, ASA plus PPI resulted in fewer lifetime UGIB events (3.4% vs. 7.2%) and increased ASA adherence (74% vs. 71%). Increased ASA adherence resulted in fewer recurrent MIs (26 fewer events per 10000 patients). On average, the ASA plus PPI strategy resulted in 38 additional days of life per patient, with the majority of this benefit (61%) because of a reduction in CV mortality (rather than UGIB-related mortality). ASA plus PPI was also more costly than ASA alone, with an ICER of $19000 per life-year saved. Results were sensitive to cost of PPI and impact of PPI on ASA adherence. Proton pump inhibitor co-therapy has the potential to impact not only GI, but also CV outcomes in patients with CV disease using ASA and such co-therapy is likely to be cost-effective. Future studies should better quantify the CV benefits of PPI co-therapy.

T1149 Risk of Upper Gastrointestinal Bleeding in Clopidogrel and Aspirin Users Receiving Concomitant Proton Pump Inhibitors

Background and aims: Clopidogrel and aspirin (ASA) are wildly used in the prevention of cardiovascular and embolic events. However, these combined medications cause significant risk of peptic ulcers and bleeding complications. This case-control study was designed to evaluate the risk of upper gastrointestinal bleeding (UGIB) in clopidogrel and aspirin users who continue receiving standard dose of proton pump inhibitors (PPI). . Methods: Data for clinical information and endoscopic findings were collected during January 2009 and November 2009 from patients who used clopidogrel and/or ASA and continue receiving standard dose of PPI. Patients with history of prior UGIB or abdominal surgery were excluded. Clopidogrel or ASA user was defined as consumption of clopidogrel or ASA for at least 7 days period preceding the episode of bleeding. The UGIB was defined as overt bleeding (hematemesis, positive nasogastric aspirate, and melena) or fall in baseline hematocrit ≥ 5 points within 24 hours of admission. Ulcer was defined at endoscope by breaking mucosa > 3mm in diameter. Results:A total of 175 patients (82 men and 93 women, mean age of 65.3 years) were evaluated in this study including 54 patients (30.9%) with UGIB and 121 patients (69.1%) with dyspeptic symptoms. Male were significantly more common than female patients in bleeding group (61.1 % vs 38.9%: P=0.01). However, the underlying diseases of the patients including cardiovascular diseases, rheumatological diseases and diabetes mellitus were not different between these 2 groups. UGIB was significantly higher in current ASA (325mg) plus clopidogrel user than non-user (16.7% vs 5.8%; P=0.02). The multivariable model suggested that the probability of UGIB event increased with current ASA (325mg) plus clopidogrel use (OR= 2.3, 95%CI =1.2-3.9) in the patients receiving concomitant PPI. Summary: Risk of UGIB events still occur in ASA and clopidogrel users in spite of receiving concomitant PPI. Lower dose of ASA, concomitant higher dose PPI and carefully monitoring of UGIB should be considered in combined ASA and clopidogrel user patients.

T1150 Role of Cyclooxygenase-2 in Cancer Stem Cell Biology and Effect of COX-2 Inhibitors in Anti-Cancer Therapy Targeting Cancer Stem Cells

Background and aims: Clopidogrel and aspirin (ASA) are wildly used in the prevention of cardiovascular and embolic events. However, these combined medications cause significant risk of peptic ulcers and bleeding complications. This case-control study was designed to evaluate the risk of upper gastrointestinal bleeding (UGIB) in clopidogrel and aspirin users who continue receiving standard dose of proton pump inhibitors (PPI). . Methods: Data for clinical information and endoscopic findings were collected during January 2009 and November 2009 from patients who used clopidogrel and/or ASA and continue receiving standard dose of PPI. Patients with history of prior UGIB or abdominal surgery were excluded. Clopidogrel or ASA user was defined as consumption of clopidogrel or ASA for at least 7 days period preceding the episode of bleeding. The UGIB was defined as overt bleeding (hematemesis, positive nasogastric aspirate, and melena) or fall in baseline hematocrit ≥ 5 points within 24 hours of admission. Ulcer was defined at endoscope by breaking mucosa > 3mm in diameter. Results:A total of 175 patients (82 men and 93 women, mean age of 65.3 years) were evaluated in this study including 54 patients (30.9%) with UGIB and 121 patients (69.1%) with dyspeptic symptoms. Male were significantly more common than female patients in bleeding group (61.1 % vs 38.9%: P=0.01). However, the underlying diseases of the patients including cardiovascular diseases, rheumatological diseases and diabetes mellitus were not different between these 2 groups. UGIB was significantly higher in current ASA (325mg) plus clopidogrel user than non-user (16.7% vs 5.8%; P=0.02). The multivariable model suggested that the probability of UGIB event increased with current ASA (325mg) plus clopidogrel use (OR= 2.3, 95%CI =1.2-3.9) in the patients receiving concomitant PPI. Summary: Risk of UGIB events still occur in ASA and clopidogrel users in spite of receiving concomitant PPI. Lower dose of ASA, concomitant higher dose PPI and carefully monitoring of UGIB should be considered in combined ASA and clopidogrel user patients.

The economics of upper gastrointestinal bleeding in a US managed-care setting: a retrospective, claims-based analysis

Objective: To assess 12-month healthcare resource utilization and costs associated with upper gastrointestinal (UGI) bleeding events.Methods: Patients hospitalized with a UGI bleeding event were identified in US national health-plan claims data (1999–2003) and propensity matched to control patients without UGI bleeding in the same health plan. Matching criteria included age, gender, index date, Charlson Comorbidity Index score, geographic region, and prior medical utilization.Results: A total of 9,033 UGI-bleed patients and 579,018 control patients met the inclusion criteria, yielding 4,651 matched pairs. After matching, differences between the UGI bleed and general population cohorts remained for office visits, ER visits, and ER costs during the 6-month baseline period prior to the index date. During the 12 months following the index date, both UGI-related healthcare utilization and total healthcare, medical, and pharmacy costs incurred by the UGI-bleed cohort were significantly greater (p< 0.0001) than those incurred by the general population cohort (mean of $20,405 vs. 3,652), even after excluding the initial hospitalization costs (mean of $11,228 vs. 3,652). Costs were primarily due to inpatient hospitalizations (mean of $13,059 for the UGI-bleed cohort vs. $729 for the general population cohort) and ambulatory services (mean of $4,037 for the UGI-bleed cohort vs. $1,537 for the general population cohort). Sixteen percent of the UGI-bleed cohort had a GI-related hospitalization, and about 40% of total costs occurred after the initial hospitalization.Conclusions: Patients with UGI bleeds experienced significantly higher (p< 0.0001) 12-month health-resource utilization and costs than patients without UGI bleeds. This study provides empirical evidence of the long-term economic burden associated with UGI bleeding. Interpretation of the results should take into account the lack of available information in claims data that could have an effect on study outcomes, such as particular clinical and disease-specific parameters that are not mitigated by propensity score and comorbidity index matching. In addition, this study is limited by the intensive demographic matching that was done between the two cohorts, which may have eliminated the sickest UGI patients and the healthiest general health-plan population patients.

The EU-ADR project: preliminary results and perspective.

The EU-ADR project aims to exploit different European electronic healthcare records (EHR) databases for drug safety signal detection. In this paper we describe the project framework and the preliminary results. As first step we created a ranked list of the events that are deemed to be important in pharmacovigilance as mining on all possible events was considered to unduly increase the number of spurious signals. All the drugs that are potentially associated to these events will be detected via data mining techniques. Data sources are eight 8 databases in four countries (Denmark, Italy, the Netherlands, and the United Kingdom) that are virtually linked through harmonisation of input data followed by local elaboration of input data through custom-built software (Jerboa). All the identified drug-event associations (signals) will be thereafter biologically substantiated and epidemiologically validated. To date, only Upper gastrointestinal bleeding (UGIB) event has been used to test the ability of the system in signal detection. An initial ranked list comprising 23 adverse events was identified. The top-ranking events were: cutaneous bullous eruptions, acute renal failure, acute myocardial infarction, anaphylactic shock, and rhabdomyolysis. Regarding the UGIB test, a total of 48,016 first-ever episodes were identified. The age-standardized incidence rates of UGIB varied between 40-100/100,000 person-years depending on country and type of healthcare database. A statistically significant association between use of NSAIDs and UGIB was detected in all of the databases. a dynamic ranked list of 23 adverse drug events judged as important in pharmacovigilance was created to permit focused data mining. Preliminary results on the UGIB event detection demonstrate the feasibility of harmonizing various health care databases in different European countries through a distributed network approach.

Cost-effectiveness of Proton Pump Inhibitor Cotherapy in Patients Taking Long-term, Low-Dose Aspirin for Secondary Cardiovascular Prevention

Patients with coronary heart disease (CHD) require long-term therapy with low-dose aspirin (ASA). Although these patients are at increased risk for upper gastrointestinal bleeding (UGIB) and proton pump inhibitor (PPI) cotherapy may reduce such risk, it is not known whether lifelong PPI cotherapy is cost-effective. A Markov model was developed to compare lifelong therapy with ASA alone vs therapy with ASA plus PPI in patients with CHD who are at least 50 years old. Base-case assumptions were (1) starting age, 65 years (range, 50-80 years); (2) UGIB risk category, average risk (range, average to 8-fold increased risk); (3) PPI effectiveness (66% (range, 25%-75%); and (4) annual PPI cost, $250 (range, $250-$1400). In the base-case analysis, ASA plus PPI resulted in fewer lifetime UGIB events (3.1% vs 9.5%) and UGIB-related deaths (0.4% vs 1.4%). At over-the-counter (OTC) PPI cost, ASA plus PPI was cost-effective, with an incremental cost-effectiveness ratio (ICER) of $40,090 per life-year saved (LYS). Varying PPI effectiveness from 75% to 25% resulted in ICERs of $35,315 to $94,578 per LYS. Varying the starting age of the cohort from 80 to 50 years resulted in ICERs of $16,887 to $79,955 per LYS. At prescription PPI cost, the ICER for average-risk patients was over $100,000 per LYS across all modeled age groups and assumptions of PPI effectiveness, but the ICER for high-risk patients was $10,433 to $51,505 per LYS. At OTC cost, PPI cotherapy is cost-effective in average-risk patients taking low-dose ASA for secondary prevention. At prescription cost, cotherapy is cost-effective for high-risk patients only.