Higher Risk Of Upper Gastrointestinal Bleeding Research Articles

Prescribing of Proton Pump Inhibitors for Prevention of Upper Gastrointestinal Bleeding in US Outpatient Visits

Antisecretory medications, primarily proton pump inhibitors (PPIs), have proven effective in reducing upper gastrointestinal toxicities, including upper gastrointestinal bleeding (UGIB), associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are among the most commonly used medications in the United States.1 Accordingly, professional guidance recommends PPIs for patients at high risk for UGIB.2-4 However, little is known about trends in use of antisecretory medications for gastrointestinal prophylaxis ("gastroprotection"). Herein, we examined contemporary use and prescribing of antisecretory medications in visits by patients at high risk for UGIB, relative to visits by patients diagnosed with acid-related disorders.

Time for Routine Helicobacter pylori Screening in Coronary Artery Disease?

Time for Routine Helicobacter pylori Screening in Coronary Artery Disease?

Upper gastrointestinal bleeding in patients with liver cirrhosis

Upper gastrointestinal bleeding (UGIB) is a potentially life-threatening emergency that remains a common cause of admission to hospital for cirrhotic patients. This re­tro­s­pec­tive study included 230 patients, over a period of two years, who presented with UGIB and underwent emer­gen­cy gastroscopy at the County Emergency Clinical Hos­pi­tal Târgu-Mureş. The patients were divided into two groups (patients with variceal bleeding versus non-variceal ble­eding, and alcoholic cirrhosis versus viral cirrhosis). Com­­pa­ri­sons were made to identify the sources of digestive ble­eding, the risk factors and the clinical outcomes, such as mortality, need for transfusion and hemostasis. This study shows that esophageal varices are the main cause of UGIB in cirrhotic patients regardless the etiology, but al­most a half experience bleeding from a non-variceal source, the most common being peptic ulcer. Bleeding from a non-variceal source is as severe as variceal rupture, re­­quir­­ing the same number of transfusions, with a similar rate of rebleeding and mortality. Male young patients with al­co­ho­lic cirrhosis have a higher risk of UGIB and need more trans­fu­sions than in patients with viral cirrhosis. The large num­ber of patients requiring endoscopic hemostasis re­veals the importance of upper digestive endoscopy to specify the etio­lo­gy and establish the appropriate treat­ment.

Delay in Retreatment of Helicobacter pylori Infection Increases Risk of Upper Gastrointestinal Bleeding

Little is known about risk of upper gastrointestinal bleeding (UGIB) in patients failed by Helicobacter pylori eradication therapy. We investigated the effects of different time until retreatment, after failure of initial Hpylori eradication therapy, on subsequent risk of UGIB. We performed a territory-wide retrospective cohort study of 70,518 patients with H pylori infection who had received their first course of clarithromycin-based triple therapy from January 2003 through December 2012 in Hong Kong. Patients who required retreatment after failed initial therapy (n = 8330, 11.8%) were categorized based on time between initial and final H pylori eradication (3 months or less, 3-12 months, and more than 12 months). We collected clinical data from 30 days after prescription of the last course of H pylori therapy until hospitalization for non-variceal UGIB, death, or the end of the study (30 Jun 2016; median follow-up time, 7.65 years). The primary outcome was difference in development UGIB (determined from ICD-9 codes) between patients who required retreatment and those who did not (reference group). Compared with the reference group, patients who required retreatment had an overall higher risk of UGIB, even after last eradication therapy (adjusted hazard ratio (HR), 1.50, 95% CI, 1.34-1.69). There was a progressive increase in risk of UGIB with longer time from initial until final eradication therapy: hazard ratio for time less than 3 months, 1.16; 95% CI, 0.88-1.54, hazard ratio for time 3-12 months, 1.35; 95% CI, 1.07-1.69, and hazard ratio for time more than 12 months, 1.68; 95% CI, 1.46-1.94 (P for trend= .038). In a retrospective study of patients in Hong Kong, we found that those failed by initial H pylori eradication have an increased risk of UGIB, compared to patients who responded to the initial therapy. Risk increased progressively with longer time until retreatment. Early retreatment within 3 months should be considered to minimize subsequent UGIB risk.

Physicians' Perceptions of Proton Pump Inhibitor Risks and Recommendations to Discontinue: A National Survey.

To provide contemporary estimates of internists' perceptions of adverse effects associated with proton pump inhibitors (PPIs) and self-reported clinical use. We invited 799 internists, including specialists and postgraduate trainees, to complete an online survey. Topics included perceptions of PPI adverse effects (AEs) and effectiveness for upper gastrointestinal bleeding (UGIB) prevention, changes in prescribing, and management recommendations for patients using PPIs for gastroesophageal reflux disease or UGIB prevention. We used logistic regression to identify factors associated with appropriate PPI continuation in the scenario of a patient at high risk for UGIB. Among 437 respondents (55% response rate), 10% were trainees and 72% specialized in general medicine, 70% were somewhat/very concerned about PPI AEs, and 76% had somewhat/very much changed their prescribing. A majority believed PPIs increase the risk for 6 of 12 AEs queried. Fifty-two percent perceived PPIs to be somewhat/very effective for UGIB prevention. In a gastroesophageal reflux disease scenario in which PPI can be safely discontinued, 86% appropriately recommended PPI discontinuation. However, in a high-risk UGIB prevention scenario in which long-term PPI use is recommended, 79% inappropriately recommended discontinuation. In this latter scenario, perceived effectiveness for bleeding prevention was strongly associated with continuing PPI (odds ratio 7.68, P < 0.001 for moderately; odds ratio 17.3, P < 0.001 for very effective). Other covariates, including concern about PPI AEs, had no significant association. Most internists believe PPIs cause multiple AEs and recommend discontinuation even in patients at high risk for UGIB. Future interventions should focus on ensuring that PPIs are prescribed appropriately according to individual risks and benefits.

Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction.

Guidelines differ in their recommendations on therapy to prevent gastrointestinal bleeding for patients treated with dual antiplatelet treatment (DAPT). We sought to investigate the effectiveness of proton pump inhibitors (PPIs) to prevent upper gastrointestinal (UGI) bleeding in patients using DAPT following myocardial infarction (MI) in relation to current European Society of Cardiology guidelines recommendations. We linked Danish nationwide registries to identify patients taking DAPT 7 days following hospital discharge for an acute MI, and excluded individuals on anticoagulation therapy. We used multiple Cox regression modelling, to compute average risk of UGI bleeding in relation to PPI use. The associated treatment efficacy was compared based on guideline risk assessment. We studied 46301 patients on DAPT after MI. Only 35% of patients at higher risk of UGI bleeding received recommended treatment with a PPI based on the guideline criteria. The 1--year risk of UGI bleeding was 1.0% [95% confidence interval (CI) 0.9-1.1%] and 1.7% (CI 1.5-2.0%) for high-risk patients. Overall PPI compared with no therapy, was associated with a risk ratio for UGI bleeding of 0.62 (CI 0.48-0.77) corresponding to an absolute risk difference of 0.44% (CI 0.39-0.48%). Proton pump inhibitor therapy was associated with a similar absolute risk difference [0.47% (CI 0.43-0.51%)] for high-risk patients. Proton pump inhibitor therapy is used less than suggested by guidelines in patients treated with DAPT following MI and was generally associated with reduced risk of UGI bleeding. Considering the overall low risk of bleeding, more focus should be on identifying patients benefiting the most from PPI therapy.

Patients' Perceptions of Proton Pump Inhibitor Risks and Attempts at Discontinuation: A National Survey.

Little is known about how reports on the adverse effects of proton pump inhibitors (PPIs) impact patients' perceptions of these drugs and medication use. We sought to determine patients' level of concern about PPI adverse effects and its association with attempts to discontinue these drugs. This study is an online survey of US adults who use PPIs for gastroesophageal reflux disease. Topics included awareness of and concern about PPI adverse effects, prior discussion with providers, and attempts to stop PPI because of concern about adverse effects. For the primary analysis, we used logistic regression to identify associations between having attempted to stop PPI and concern about PPI-related adverse effects, a provider's recommendation to stop, risk of upper gastrointestinal bleeding (UGIB), age, and gender. Among 755 patient participants, mean age was 49 years (s.d. 16), 71% were women, and 24% were at high risk of UGIB. Twenty percent of patients were able to write in ≥1 reported adverse effect, and 46% endorsed awareness of ≥1 adverse effect when presented with a list, most commonly chronic kidney disease (17%). Thirty-three percent of patients were slightly concerned, 32% somewhat concerned, and 14% extremely concerned about adverse effects. Twenty-four percent of patients had discussed PPI risks and benefits with a provider, and 9% had been recommended to stop. Thirty-nine percent had attempted to stop their PPI, most (83%) without a provider recommendation. Factors associated with an attempt at stopping PPI included: (i) provider recommendation to stop (odds ratio [OR] 3.26 [1.82-5.83]); (ii) concern about adverse effects (OR 5.13 [2.77-9.51] for slightly, 12.0 [6.51-22.2] for somewhat, and 19.4 [9.75-38.7] for extremely concerned); and (iii) female gender (OR 1.64 [1.12-2.39]). Patients at high risk of UGIB were as likely to have attempted to stop as others (OR 0.98 [0.66-1.44]). Concern about PPIs is common and strongly associated with attempts at discontinuation, even without a provider's recommendation. Notably, individuals at high risk of UGIB, who benefit from PPIs, were equally likely to have tried stopping PPIs as others. Providers should proactively discuss the risks and benefits of PPIs with their patients, who may otherwise make unwise decisions about PPI management on their own.

Abstract 17718: New Oral Anticoagulants: Bleeding Rates Among Medicare Beneficiaries With Atrial Fibrillation

Introduction: In randomized trials of patients with non-valvular atrial fibrillation (AF), new oral anticoagulants (NOACs) have been shown to confer a lower risk of major bleeding than warfarin. Outside of these select study settings, bleeding outcomes for these medications have not been examined sufficiently. We studied a national sample of patients with AF to explore bleeding risks associated with NOACs in routine clinical settings. Methods: Using a 40% Medicare random sample denominator file and associated inpatient, outpatient and prescription administrative data from 2009-2012, we identified patients age 65 and older with new onset, non-valvular AF. Cox regression models estimated risk of upper gastrointestinal (UGI) and nontraumatic intracranial (IC) bleeding associated with NOAC (dabigatran and rivaroxaban) compared to warfarin use, adjusting for individual characteristics, morbidities, and time-varying medication use. The analysis excluded person-months with concurrent prescriptions filled for an antiplatelet medication (e.g. clopidogrel). Results: We identified 157,390 incident AF patients, mean age 77.8 (standard deviation (SD) 7.8); mean follow up was 10.8 months (SD 6.9); In the first year post-index diagnosis, 41.5% of patients received some oral anticoagulant; of these, 28.2% used NOACs (75% dabigatran, 25% rivaroxaban). Overall 24,661 bleeding events were observed (11,015 UGI and 1,868 IC). Out of 1,487,675 person-months, 212,670 (14.3%) were excluded due to concurrent prescription antiplatelet exposure. Compared to warfarin, the hazard ratio for bleeding associated with NOAC was 1.33 (95% CI 1.21 to 1.47) for UGI, 0.59 (95% CI 0.42 to 0.82) for IC, and 1.09 (95% CI 1.02, 1.17) for all significant bleeding combined. Conclusions: Compared with warfarin, NOACs were associated with a lower risk of IC bleeding, a higher risk of UGI bleeding and a modestly higher risk of significant bleeding overall. These results should inform clinical decision-making and selection of individualized thromboembolism prophylaxis strategies among AF patients. Further studies are needed to illuminate the divergent UGI and IC bleeding risks observed and to identify patient-level factors predictive of these outcomes.

Defining Appropriate Use of Proton-Pump Inhibitors Among Medical Inpatients.

Proton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal bleeding (UGIB) and continuation of outpatient use. While PPIs reduce the risk of UGIB, they also appear to increase the risk of hospital-acquired pneumonia (HAP) and Clostridium difficile infection (CDI). Depending upon the underlying risks of these conditions and the changes in those risks with PPIs, use of proton-pump inhibitors may lead to a net benefit or net harm among medical inpatients. We aimed to determine the net impact of PPIs on hospital mortality among medical inpatients. A microsimulation model, using literature-derived estimates of the risks of UGIB, HAP, and CDI among medical inpatients, along with the changes in risk associated with PPI use for each of these outcomes. The primary outcome was change in inpatient mortality. Simulated general medical inpatients outside the intensive care unit (ICU). Change in overall mortality during hospitalization. New initiation of PPI therapy led to an increase in hospital mortality in about 90% of simulated patients. Continuation of outpatient PPI therapy on admission led to net increase in hospital mortality in 79% of simulated patients. Results were robust to both one-way and multivariate sensitivity analyses, with net harm occurring in at least two-thirds of patients in all scenarios. For the majority of medical inpatients outside the ICU, use of PPIs likely leads to a net increase in hospital mortality. Even in patients at particularly high risk of UGIB, only those at the very lowest risk of HCAP and CDI should be considered for prophylactic PPI use. Continuation of outpatient PPIs may also increase expected hospital mortality. Apart from patients with active UGIB, use of PPIs in hospitalized patients should be discouraged.

Prevalence and risk factors for clinically significant upper gastrointestinal bleeding in patients with severe acute pancreatitis.

To investigate the prevalence and risk factors of upper gastrointestinal bleeding (UGIB) in patients with severe acute pancreatitis (SAP). Altogether 101 patients were admitted to the Department of Gastroenterology, Changhai Hospital, Second Medical Military Hospital from July 2006 to June 2010 due to SAP. Their prevalence and risk factors of UGIB were retrospectively analyzed. In total, 18 (17.8%) patients developed UGIB and 13 received endoscopic examination, which yielded six cases of acute gastric mucosal lesions (AGML), five of peptic ulcers (PU) and two of pancreatic necrotic tissue invading the duodenal bulb and presenting as multilesion, honeycomb-like ulcer. The mortality rate of UGIB patients was much higher than that of non-UGIB patients (44.4% vs 10.8%, P = 0.0021). Univariate analysis revealed that the risk factors for UGIB included the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, computed tomography severity index (CTSI), Ranson score, arterial blood pH and PaO2 , serum blood urea nitrogen and creatinine concentrations, platelet count, shock, sepsis and organ failure, mechanical ventilation, heparinized continuous renal replacement therapy and total parenteral nutrition. Multivariate logistic regression revealed that APACHE II score and CTSI were significant risk factors while PaO2 was the protective factor for UGIB in SAP. UGIB is a common complication with poor prognosis due mainly to PU and AGML. Patients having SAP with high APACHE II scores and CTSI or low PaO2 should be considered to be at high risk for UGIB.

An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding

In vitro studies have shown that selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation. It is controversial whether use of SSRIs is a cause of clinically important bleeding; results from observational studies have been equivocal. A population-based case-control study was conducted in Denmark. The 3652 cases all had a first discharge diagnosis of serious upper gastrointestinal bleeding (UGB) from 1995 to 2006. Controls (n = 36,502), matched for age and sex, were selected by risk-set sampling. Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by conditional logistic regression and the case-crossover design. The adjusted odds ratio (OR) of UGB among current, recent, and past users of SSRIs was 1.67 (95% confidence interval [CI], 1.46-1.92), 1.88 (95% CI, 1.42-2.5), and 1.22 (95% CI, 1.07-1.39). The adjusted OR for concurrent use of SSRI and nonsteroidal anti-inflammatory drugs (NSAIDs) was 8.0 (95% CI, 4.8-13). The adjusted OR for the concurrent use of NSAID, aspirin, and SSRI was 28 (95% CI, 7.6-103). Of the UGB cases, 377 were current users of SSRI; the adjusted OR for UGB in the case crossover analysis was 2.8 (95% CI, 2.2-3.6). The adjusted OR among users of proton pump inhibitors was 0.96 (95% CI, 0.50-1.82). Use of SSRI was associated with UGB, consistent with its antiplatelet effects. SSRIs should be prescribed with caution for patients at high risk for UGB.

Risk factors for upper gastrointestinal bleeding among end-stage renal disease patients

The risk of upper gastrointestinal bleeding (UGIB) is increased among end-stage renal disease (ESRD) patients compared to the general population. However, correlates of UGIB among ESRD patients remain unknown. We conducted a cohort study of dialysis patients to ascertain risk factors for UGIB. Data from the United States Renal Data System Dialysis Morbidity and Mortality Studies, Waves 2-4 were used to identify risk factors for incident UGIB among ESRD patients. First hospitalizations for UGIB were identified using hospital diagnosis codes between 12/31/93 and 12/31/99. Cox regression was used to estimate the association between predictors of interest and first diagnosis of UGIB. Cases of UGIB (698) were observed over 30648 patient years of follow-up. Before adjustment for confounding factors, increasing age, diabetes, former and current smoking, cardiovascular disease (CVD), lower serum albumin, malnutrition, and inability to ambulate independently were associated with an increased risk of UGIB, while African Americans and transplant patients had a lower risk of UGIB. After adjustment, African American race was associated with a lower risk of UGIB (RR = 0.90; 0.82, 0.98), while current smoking (RR = 1.11; confidence interval 1.03, 1.19), history of CVD (RR = 1.32; 1.10, 1.59), and inability to ambulate independently (RR = 1.32; 1.07, 1.63) were associated with a higher risk of UGIB. Age, gender, diabetes, lower serum albumin, nourishment, treatment modality, aspirin use, nonsteroidal anti-inflammatory drug (NSAID) use, and antiplatelet or anticoagulant medication use were not found to be significantly related to the risk of UGIB after adjustment for potential confounding factors. CVD, current smoking, and risk factors suggesting more disability are associated with a greater risk of UGIB among patients with ESRD.

Risk of upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases.

Most patients with vascular-occlusive diseases benefit from low-dose aspirin (75-325 mg/day). However, they have an increased risk of upper gastrointestinal bleeding (UGIB). To analyse the incidence and factors influencing the occurrence of UGIB in patients taking low-dose aspirin for the prevention of cardiovascular diseases outside clinical trials. We studied 903 consecutive patients discharged on low-dose aspirin from the Cardiology Department of a general hospital. Data were collected from medical charts and structured telephone interviews. Forty-one patients (4.5%) presented with UGIB requiring hospitalization during follow-up (45 +/- 22 months). The incidence of UGIB was uniform during follow-up (1.2 UGIB per 100 patient years). Multivariate analysis showed that a history of peptic ulcer or UGIB [risk ratio: 3.1, 95% CI: (1.5-6.5)] and aspirin dose (per 100 mg/day) [1.8 (1.5-2.9)] was associated with higher risk of UGIB. On the other hand, antisecretory [0.22 (0.07-0.75)] and nitrovasodilator drugs [0.73 (0.55-0.96)] were associated with a decreased risk. Cardiovascular patients on long-term low-dose aspirin have a stable risk of major UGIB, which is higher than published controlled clinical trials. Antisecretory and nitrovasodilator drugs protect from UGIB, whereas previous peptic ulcer or UGIB and higher doses of aspirin increase the risk.