The changing face of non‐variceal, upper gastrointestinal hemorrhage

See article in J. Gastroenterol. Hepatol. 2007; 22: 13–17. Many gastroenterologists feel that changes have occurred in the demographic features and pattern of illness in patients who present with hematemesis and melena. One common impression is that there has been a progressive fall in the incidence of bleeding from typical duodenal and gastric ulcers. Another impression is that patients with hematemesis and melena are now older, sicker and more likely to be on anticoagulant medication. A third impression is that endoscopic therapy is useful for control of bleeding but that patients still die because of coexisting medical disorders such as advanced cardiac and respiratory disease. Are these impressions supported by facts? Unfortunately, there are only a small number of epidemiological studies that have addressed the annual incidence of upper gastrointestinal bleeding. In the 1990s, two large population-based studies in the UK estimated the annual incidence of hospital admission for upper gastrointestinal bleeding at 103 and 172 per 100 000 population, with higher incidence rates in lower socio-economic areas.1,2 In 1991, the incidence of hospital admission for bleeding was 102 per 100 000 members of a health maintenance organization in San Diego.3 However, lower incidence rates of 45–61.7 per 100 000 population have been reported from the Amsterdam area.4,5 Furthermore, this incidence decreased from 61.7 per 100 000 in 1993–1994 to 47.7 per 100 000 in 2000, a decrease of 23% after adjustment for age.5 This period corresponds to the widespread use of eradication regimes for Helicobacter pylori and the increasing use of cyclooxygenase-2 (COX-2) inhibitors rather than non-selective, non-steroidal anti-inflammatory drugs (NSAIDs). In Canada, however, the increasing use of COX-2 inhibitors from 2000 to 2002 did not decrease the frequency of hospital admissions for bleeding in patients over the age of 65 years.6 In relation to age and sex, recent surveys clearly show a striking increase in the incidence of upper gastrointestinal bleeding with advancing age. For example, in one study, the incidence in patients over 75 years was almost six-fold higher than in patients aged 15–29.2 In studies published since 1990, the mean age of patients at presentation is almost always in the range of 65–70 years.5,7 Typically, men are more commonly affected than women with a ratio of 1.5:1 (60% men, 40% women) despite a predominance of women in older age groups in the general population. This sex effect has not been clearly explained but could be related to smoking, hormonal effects on susceptibility to peptic ulceration or perhaps to gender-effects on the use of acid-suppressants, NSAIDs or anticoagulants. A comparison of contemporary studies with older publications indicates that there has been a progressive increase in the mean age of patients presenting with upper gastrointestinal bleeding over the past 80 years. For example, prior to 1930, fewer than 10% of patients were aged greater than 60 years.8 After the advent of flexible endoscopy in the 1970s, the mean age of patients had increased to 50–60 years.9–12 These studies also showed a higher ratio of men to women, typically 2:1 but sometimes increasing to 3:1. Many of these studies had substantial numbers of middle-aged men with duodenal ulcers.12 Changes also appear to have occurred in the cause of upper gastrointestinal bleeding, particularly in relation to the frequency of gastric and duodenal ulcers. However, an on-going issue in this area is variation in endoscopic criteria for diagnosing ulcers and differentiating ulcers from superficial erosions. Despite this controversy, several studies in the 1970s showed that at least 44% of episodes of bleeding were due to gastric or duodenal ulcers.9–12 More recent studies, however, indicate that the frequency of ulcers has decreased to 20–30%.7,13 This has been associated with an increase in the frequency of diagnoses such as gastric and duodenal erosions, hemorrhagic gastritis and ‘stress-related mucosal disease’. In the Clinical Outcomes Research Initiative (CORI database), these abnormalities have been grouped as ‘mucosal abnormalities’ and now account for at least 40% of episodes of gastrointestinal bleeding.13 In relation to the relative frequency of gastric and duodenal ulcers, time-trend analyses indicate that the lower frequency of peptic ulcers is largely due to a decline in duodenal ulcers.14,15 An historical perspective on upper gastrointestinal bleeding also needs to encompass the introduction of drugs that increase and decrease the risks of peptic ulceration as well as the increasing use of anticoagulant drugs that may increase the risk of severe bleeding. For example, drugs that increase the risk of peptic ulceration and bleeding include aspirin, non-salicylate NSAIDs and perhaps COX-2 inhibitors. For aspirin and NSAIDs, risks for bleeding are dose related (and perhaps drug related) and there are additional risks for advanced age, previous peptic ulcer disease, and use of anticoagulants. Overall, low-dose aspirin and NSAIDs increase the risk of bleeding by 2–3-fold and 4–6-fold, respectively.16,17 Anticoagulants such as warfarin and clopidogrel also increase the risk of bleeding, particularly in patients with previous episodes of bleeding or previous peptic ulceration.18,19 Furthermore, there are additional risks for bleeding when warfarin is used concomitantly with NSAIDs.20 In contrast, there are reduced risks for ulceration and bleeding with the longer-term use of acid-suppressant medication and perhaps nitrovasodilator drugs.21 The most potent acid-suppressants, proton pump inhibitors, also reduce the risks of ulceration and bleeding in patients who are taking low-dose aspirin and NSAIDs.22,23 Over the past 15 years, there have been important developments in the management of patients with upper gastrointestinal bleeding. These include improved emergency resuscitation, specialized nursing care, new drugs and effective endoscopic treatment for bleeding. This has been associated with a reduction in the surgical rate from 15–35% in the 1970s12 to 4–10% in recent studies.5,7 Unfortunately, these developments do not appear to have been associated with an improvement in mortality. For example, studies in the 1970s reported mortality rates of approximately 10%.12 In more recent studies, these rates have ranged from 7% to 15%.5,7 In time-trend analyses, mortality rates remained constant in the Amsterdam area between 1993–1994 and 2000,5 but improvements in mortality have been achieved at individual hospitals.7 One important determinant of mortality is the percentage of patients with bleeding esophageal varices, a disorder with a mortality of approximately 20% during the first admission. Other predictors of mortality include advanced age, increasing comorbidity (including higher APACHE scores), rebleeding in hospital and endoscopic stigmata associated with high risks for rebleeding.24 Because of wide variation in categorizing causes of death, it is not possible to determine whether more recent studies have a higher percentage of patients whose death is largely due to coexisting disorders. In this issue of the Journal, Chen et al.25 report a retrospective study of upper gastrointestinal bleeding in patients with known ischemic heart disease who were receiving treatment with aspirin. Patients were divided into two groups based on the presence or absence of ischemic changes on an electrocardiograph in the emergency department. Ischemic changes were detected in 31 of 152 patients (20.4%), at least two of whom had a silent myocardial infarct. Patients with ischemic changes had a higher heart rate and blood urea nitrogen and a lower hematocrit and diastolic blood pressure. Some of these markers are consistent with greater degrees of blood loss. Endoscopy was performed without complication but myocardial ischemia was associated with longer hospital lengths of stay and higher in-hospital mortality (16.1% vs 2.5%). Although causes of death were not included in the aforementioned study, the clear message is that the coexistence of myocardial ischemia and upper gastrointestinal bleeding is associated with higher mortality. Whether this is largely due to major bleeding, cardiac complications or postoperative deaths remains to be determined by prospective studies. These patients need not only early intensive resuscitation26 and skilled endoscopic management, but also on-going care by physicians competent in several areas of internal medicine. We are grateful to Dr KR Palmer, Edinburgh, for helpful comments.

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