Theresa Craigen

Mortality following blood transfusion for non-variceal upper gastrointestinal bleeding

Objective Blood transfusion remains an integral step in the management of acute non-variceal upper gastrointestinal bleeding (NV-UGIB), but its safety is being increasingly questioned in less severe cases. The authors aimed to measure 30-day and 2-year mortalities after blood transfusion for NV-UGIB. Methods Cox proportional hazards models were used to estimate the association of blood transfusion with mortality while adjusting for age, Charlson comorbidity score, the complete Rockall score for acute UGIB, admission status and medication intake prior to bleeding. Main outcome measures Death from any cause at 30 days and 2 years after NV-UGIB. Results 1340 patients presented with NV-UGIB< (808 men (60.3%), median age 67 years) of whom 564 (42.1%) were transfused. The overall mortality was 5.3% at 30 days and 26.0% at 2 years in all patients. Comparing subjects with a haemoglobin concentration greater than 10.0 g/dl who were transfused with those who were not, 30-day mortalities (95% CIs) were 11.5% (6.7 to 18.0) versus 3.6% (2.3 to 5.3), respectively, p<0.001, and 2-year mortalities (95% CIs) were 40% (32 to 49) versus 20% (17 to 23), p<0.001. After adjusting for age, Charlson score, Rockall score and haemoglobin, the HRs (95% CIs) for death after transfusion were 1.88 (1.00 to 3.55) (p=0.051) at 30 days and 1.71 (1.28 to 2.28), (p<0.001) at 2 years. Conclusion In patients with moderately severe NV-UGIB, mortality is higher following blood transfusion. Whether this reflects selection bias, an effect of comorbidity or an effect of transfusion requires urgent prospective study.

Gastro-protective policy and the incidence of upper gastrointestinal bleeding

Objectives In recent years, policies have been proposed in order to guide the safer use of non-steroidal anti-inflammatory drugs (NSAIDs) and antiulcer therapy. We aimed to investigate the incidence of upper gastrointestinal bleeding (UGIB) before and after the introduction of these policies, 2007–2009, in a well-defined population in southwest Scotland. Methods All patients with non-variceal upper gastrointestinal bleeding (NV-UGIB), diagnosed at a single regional unit, were included. Total drugs prescribed in our population were noted, including antiulcer drugs, antithrombotic drugs and both cyclo-oxygenase-2 enzyme-selective and non-selective inhibiting NSAIDs. Results The incidence, the number of cases per 100 000 population per annum, of NV-UGIB fell from 134.7 in 2007 to 125.1 in 2008, and to 90.3 cases in 2009 (p<0.001). There was also a significant rise in the use of non-selective NSAIDs, proton pump inhibitors and antithrombotic drugs. Conclusions Although a cause-and-effect relationship cannot be fully proven, physician education through drug-use policies is associated with a drop in the incidence of NV-UGIB. This is relevant to the prevention of this common condition.

Falling mortality when adjusted for comorbidity in upper gastrointestinal bleeding: relevance of multi-disciplinary care

Objectives The understanding of changes in comorbidity might improve the management of upper gastrointestinal bleeding (UGIB); such changes might not be detectable in short-term studies. We aimed to study UGIB mortality as adjusted for comorbidity and the trends in risk scores over a 14-year period. Methods Patients presenting with UGIB to a single institution, 1996–2010, were assessed. Those with multiple comorbidities were managed in a multi-disciplinary care unit since 2000. Trends with time were assessed using logistic regression, including those for Charlson comorbidity score, the complete Rockall score and 30-day mortality. Results 2669 patients were included. The Charlson comorbidity score increased significantly with time: the odds of a high (3+) score increasing at a relative rate of 4.4% a year (OR 1.044; p<0.001). The overall 30-day mortality was 4.9% and inpatient mortality was 7.1%; these showed no relationship with time. When adjusted for the increasing comorbidity, the odds of death decreased significantly at a relative rate of 4.5% per year (p=0.038). After the introduction of multi-disciplinary care, the raw mortality OR was 0.680 (p=0.08), and adjusted for comorbidity it was 0.566 (p=0.013). Conclusions 30-day mortality decreased when adjusted for the rising comorbidity in UGIB; whether this is related to the introduction of multi-disciplinary care needs to be considered.

Occult vs. overt upper gastrointestinal bleeding – inverse relationship and the use of mucosal damaging and protective drugs

While efforts have focused on the prevention of overt upper gastrointestinal bleeding (UGIB), little is known about occult GIB, which might also originate from sites not protected by acid inhibition.

Upper gastrointestinal bleeding in hospital inpatients: the role of antithrombotic drugs

Background Critically ill patients are considered to be most at risk from developing non-variceal upper gastrointestinal bleeding (NVGIB) while in hospital. The increasing prescription of low-dose aspirin and other antithrombotic drugs for protection against thromboembolism to many patients admitted to hospital may increase the vulnerability of a wider group to NVGIB. Objective This study compares two groups of patients with NVGIB: group I, inpatients cared for outside the intensive care unit; and group II, patients admitted with this condition, while considering the use of antithrombotic drugs. Methods We identified all patients who developed NVGIB in the two calendar years between 2008 and 2009 and compared group I with group II while taking into account their clinical details including Rockall scores and drug usage. Results Compared with group II (n=274), group I (n=96) were older (median age of 77 years vs 68; p<0.001), had fewer males (45.8% vs 60.6%; p=0.016), higher prevalence of cardiovascular disease (52.1% vs 29.2%; p<0.001), more patients with complete Rockall score ≥3 (84.4% vs 66.7%; p=0.001) and more patients treated with aspirin or other antithrombotic drugs (64.6% vs 44.5%; p=0.001). After adjustment for age and sex, group I were still significantly more likely to be taking antithrombotic drugs than group II (OR (95% CIs), 2.15 (1.25 to 3.68); p=0.006). The endoscopic abnormalities in more than 80% of patients included erosive oesophagitis, gastric or duodenal ulcers or erosions. Conclusions Subjects who develop NVGIB as inpatients have higher Rockall scores are mainly older females with cardiovascular disease and using antithrombotic drugs. Secondary care clinicians should be mindful of this at-risk group of patients and consider giving them prophylactic antiulcer therapy.

Small Bowel and Other GI Lesions in Obscure Gastrointestinal Bleeding and Low Dose Aspirin vs. Nsaids. Screening Phase of the Masters Trial

Introduction While NSAIDs can affect any part of the GI tract, little is known about the effect of aspirin in the small bowel or colon. In this prospective analysis, we compared upper GI, small bowel, and colonic findings in patients taking aspirin vs. those taking NSAIDs while being considered in the screening phase of the MASTERS Trial (Misoprostol for the Healing of Small Bowel Ulceration in Patients with Obscure Blood Loss while Taking Low-Dose Aspirin or Non-Steroidal Anti-inflammatory Drugs). Method For MASTERS, obscure occult bleeding was defined as having absence of potentially bleeding lesions on colonoscopy and endoscopy, and in the presence of one or more of the following: positive faecal occult blood test; iron deficiency anaemia; or drop in Hb, > 2 gm/dl from baseline. Suitable patients underwent small bowel video capsule endoscopy (Omom systems, China). Results DEMOGRAPHY: 127 patients were assessed: 80 taking aspirin alone without NSAIDs and 47 taking NSAIDs alone without aspirin; they all had colonoscopy while smaller numbers underwent upper GI or capsule endoscopy. The aspirin group had older patients (median 69 vs. 61 years, p Conclusion (1) In this prospective analysis, patients with obscure occult bleeding and using aspirin have similar prevalence and range of lesions in the small bowel and upper GI tract as those using NSAIDs. (2) The use of NSAIDs was associated with fewer patients with colonic polyps. These results might help in planning and interpreting the investigations of obscure bleeding. They might also be relevant to colon cancer chemoprevention. Disclosure of Interest None Declared

Clinical outcomes and 30-day mortality following significant upper gastrointestinal bleeding in users of anti-platelet agents and non-steroidal anti-inflammatory drugs

Introduction The use of antiplatelet agents for vascular protection continues to increase and this has been associated with serious complications including upper gastrointestinal bleeding (UGIB). The clinical outcomes following such complication remains poorly understood. We, therefore, aimed to measure 30-day mortality and other clinical outcomes in patients presenting with UGIB while using antiplatelet agents as compared with those using non-steroidal anti-inflammatory drugs (NSAIDs) and those using neither of these agents. Methods Patients were included in the analysis if they presented with haematemesis and/ or melaena and had an endoscopic abnormality to explain their UGIB. Patients were excluded if they were well enough not to require hospital admission or if they had oesophageal or gastric varices. The Charlson and the complete Rockall scores were used to measure comorbidity and assess UGIB, respectively. Death of any cause within 30 days of UGIB was recorded. Drug therapy was noted including NSAIDs and antiplatelet drugs (low-dose aspirin, clopidogrel, dipyridamole and warfarin). The χ 2 test for categorical variables and Kruskal-Wallis test for continuous variables were used. Results 990 patients entered the analysis. Their characteristics and outcomes are shown in table 1. Conclusion Patients with UGIB and taking antiplatelet drugs, with or without NSAIDs, stay longer in hospital, are more likely to require transfusion and to die within 30 days after UGIB. They are also older and have higher comorbidity and Rockall scores than bleeders not taking NSAIDs or anti-platelet agents.

Mo1268 Nicorandil Does Not Worsen Non-Variceal Upper Gastrointestinal Bleeding (NVUGIB) in Patients Taking Aspirin or Antithrombotic Drugs (ATDs)

Introduction Nicorandil is a vasodilatory drug that has the dual properties of a nitrate and K+ATP channel agonist. It is often added to ATDs in the management of angina. In light of some case reports, its manufacturer and the medicines regulatory agencies have issued cautions that it can cause mucosal ulcers, perforation and bleeding, and that these might be worse in users of aspirin. We therefore aimed to investigate the possibility that NVUGIB is more severe in patients using ATDs plus Nicorandil than ATDs alone. Methods Patients presenting with NVUGIB and using ATDs plus Nicorandil (n = 59) were compared to those using ATDs alone (Controls; n = 1056) with respect to haemoglobin level, Blatchford UGIB risk score, composite endoscopy score (covering lesions in the oesophagus, stomach and duodenum), need for blood transfusion, length of hospital admission, and 30 day mortality. ATDs included low dose aspirin, clopidogrel, dipyridamole, warfarin and heparin. Results Table 1, below, summarises the outcomes of NVUGIB and the characteristics of patients using ATDs alone vs. those using ATDs plus Nicorandil. Age and haemoglobin are shown as mean (SD), the other interval variables as median (interquartile range) and binary variables as percentage (number). The final column shows differences between groups (Nicorandil minus control) with 95% confidence intervals. All differences were statistically insignificant (P > 0.05, Student’s t, Mann-Whitney and Fisher’s exact tests as appropriate). Conclusion Patients taking ATDs plus Nicorandil were well matched demographically with controls taking ATDs alone. The confidence intervals place a modest upper limit on any exacerbation of NVUGIB by Nicorandil as manifested by reduced haemoglobin and increased need for transfusion. The intake of Nicorandil does not seem to worsen the severity or the outcomes of NVUGIB. These findings, therefore, do not justify discontinuing Nicorandil in patients with angina and presenting with NVUGIB while taking ATDs. Disclosure of Interest None Declared

414 Occult vs. Overt Upper Gastrointestinal Bleeding - Inverse Relationship and the Use of Mucosal Damaging and Protective Drugs

Introduction Efforts have been focused on the prevention of overt upper gastrointestinal bleeding (UGIB), using acid inhibitors, particularly in users of NSAIDs and anti-thrombotic therapy (ATT). Little is known about the impact of such efforts on occult GIB which might also originate from sites not protected by acid inhibition. We aimedto measure the incidence of both overt and occult GIB in a well-defined geographical region over a 5-year period, 2007–2012; assess the use of NSAIDs, ATT, PPIs, and iron therapy; and compare the outcomes of patients with occult vs. overt GIB. Method The incidence was analysed in 2007, 2010 and 2012. Overt UGIB included haematemesis and melena. A sample of 300 patients (100 from each of the 3 index years) with occult GIB was randomly selected and their outcomes and details were compared with those of patients with overt UGIB (N = 869) using the Mann-Whitney and Fisher’s exact tests. Trends with time in incidence were assessed using the chi-squared test for trend. Numbers of prescriptions issued per 1000 population were recorded for each year from 2007 to 2012 and trends were assessed using Pearson correlation analysis. Results The incidence of overt UGIB and occult GIB and details of drug use are shown in Table 1. Demography: Compared with patients with occult GIB (N = 300) randomly selected in the 3 index years, those with overt UGIB (N = 869) had a median (IQR) age of 63 (47–77) years vs. 67 (53–75) in the occult group (NS), 62.5% males vs. 39.3% (P Conclusion (1) The incidence of occult GIB continues to rise while that of overt UGIB continues to fall. (2) This is accompanied by a rise in the use of NSAIDs, PPIs, and iron therapy. (3) Patients with occult GIB have similar 30-day mortality to overt UGIB but are less likely to require blood transfusion. (4) An alternative approach to acid inhibition might be needed to prevent occult GIB. Disclosure of interest None Declared.

Sa1883 Antithrombotic vs. Ulcer Effects in Non-Variceal Bleeding in Users of Antithrombotic Drugs

Introduction The use of antithrombotic drugs (ATDs) remains a considerable challenge in the aetiology and management of non-variceal upper gastrointestinal bleeding (NVUGIB). In the upper gastrointestinal tract, ATD use may result in bleeding by mucosal damage (ulcer effect) or through its basic antithrombotic effect. The clinical significance of these effects is unclear. In this controlled analysis, we AIMED to clarify the significance of the antithrombotic effect as compared with the ulcer effect in patients with NVUGIB using ATDs. Methods We previously found that ATD users tended to be older and to have higher comorbidity and different endoscopy findings. To overcome these confounding factors, we compared 202 patients with NVUGIB using ATDs (ATD Group) with 202 patients with NVUGIB but not using ATDs (Controls), having matched both groups in a pairwise manner for age, Charlson comorbidity score and a composite endoscopic score covering the oesophagus, stomach, and duodenum. Antithrombotic drugs included low-dose aspirin, clopidogrel, dipyridamole, warfarin, and heparin. Patients using NSAIDs were excluded. Characteristics of the groups were compared using the Wilcoxon signed rank test and McNemar’s test. Continuous variables are reported as median (IQR). Results The characteristics of the two matched study groups are shown in Table 1. Conclusion After matching for age, comorbidity, and composite endoscopy score, patients with NVUGIB and using ATDs had significantly lower haemoglobin level, higher Blatchford risk score, and were 1.5 times more likely to be transfused. These effects are most likely to be due to the antithrombotic activity of ATDs rather than ulcers alone, and they need to be considered in the management of NVUGIB. Disclosure of Interest A. Taha Consultant for: Almiral Pharma UK, Vifor Pharma UK, Horizon Pharma USA, C. McCloskey: None Declared, T. Craigen: None Declared, W. Angerson: None Declared.