Pharmacy & Therapeutics - January 2009 - (Page 35) MEETING HIGHLIGHTS: United European Gastroenterology Week continued from page 32 bled, according to Dr. Lanas, who studied long-term patterns of GI complications in 10 Spanish hospitals, before clear conclusions can be stated. Dr. Lanas’ study, which included more than 30,000 patients admitted for upper and lower GI complications between 1996 and 2005, identified a distinct trend showing declining rates of upper GI events and increasing rates of lower GI events (e.g., colitis, colonic angiodysplasia, anemia caused by occult GI bleeding, small-bowel perforation). Dr. Lanas reviewed data from the study, presented also at this year’s Digestive Disease Week meeting, at a Pfizer-sponsored media roundtable entitled “The Importance of Evaluating the Entire GI Tract: Emerging Data” at the current meeting. He also discussed data confirming the link between upper GI adverse drug events such as dyspepsia and abdominal pain and endoscopically detected ulcers. Such events are leading factors for discontinuation of therapy with nonsteroidal anti-inflammatory agents (NSAIDs). Presenting a background on NSAID-associated GI toxicity, Dr. Bjarnason, the previous roundtable speaker, had stated that 1% to 4% of patients taking nonselective NSAIDS experience ulcer complications each year. Multiple and high-dose nonselective NSAID use, among the major risk factors for complications, are common in the aging population; 70% of patients 65 years of age and older take an NSAID at least once weekly. Unfortunately, ulcer complications warranting hospitalization occur most often (81%) without prior symptoms.1 Although attention has been paid predominantly to upper GI events, NSAID trials have shown lower GI events as accounting for about 40% of all GI events. Dr. Bjarnason found that NSAID enteropathy frequently included small-bowel bleeding (70%) and protein loss (70%), with an occasional incidence of perforations, bleeding ulcers, strictures, and sudden death. “The importance and clinical relevance of lower GI events are becoming increasingly acknowledged,” he said. However, even though the incidence, mortality, and costs associated with upper GI complications have been established, less is known about the lower GI tract and its related complications. Difficulties in diagnosing lower GI complications is part of the reason, he pointed out. Major recent therapeutic advances may account for the prevention of either Helicobacter pylori–induced or NSAIDinduced gastroduodenal complications, Dr. Lanas noted. Reducing acid with proton pump inhibitors (PPIs), however, does not protect the lower GI tract. He added: “While excess acid penetrates the mucosa in the stomach and does damage, we believe that bacteria are more important in small-bowel damage. You can’t just give antibiotics, though.” Dr. Lanas’ earlier research showed that GI perforation is associated with NSAID use as often in the lower GI tract as in the upper GI tract (75% lower GI, 70% upper GI). 2 His later study showed that 18,191 among 50,114 GI complications reported in 2001 were attributable to NSAID and aspirin use.3 Among 2,800 deaths reported in the overall group, more than 1,000 were attributed to NSAID with aspirin. Upper GI bleeding and lower GI bleeding were given as the cause in 5.7% and 5.3% of cases, respectively, and upper and lower GI perforations were the cause in 30.1% of cases. Dr. Lanas noted that more than 80% of the Spanish popula- tion of about 40 million uses the 10 general hospitals included in the study. The clear trend from 1996 to 2005 was of a declining estimated upper GI complication rate per 100,000 (reduced from approximately from 87 to 48 and an increasing lower GI complication rate (increased from approximately 20 to 32). Lower GI complications incurred a significantly longer hospital stay (10 or more days) than did upper GI complications (8 days) (P < 0.001). In 2005, the mortality rate per 100,000 per year for GI complications was 0.688 for upper GI complications and 0.728 for lower GI complications. Complication rates in the presence of PPI use were significantly higher in the group with complications of the lower GI tract than in those with upper GI complications (16.5% vs. 11.3%; P < 0.001). Looking at differences in risk factors for upper and lower GI complications, Dr. Lanas explained that upper GI complications are more likely to occur in younger males with fewer comorbidities and that lower GI complications are more common in older women with more comorbidities. Summarizing the trends identified by the study, he said that the ratio of upper GI versus lower GI events fell from 7:1 in 1996 to about 1.4:1 in 2005: “The clinical impact and severity of hospitalizations due to lower GI events were greater than those of upper GI events. Given these results, the evaluation of safety throughout the entire GI tract is important and has the potential to improve patient care by focusing on all GI events, rather than just some of them.” Dr. Lanas urged further study of NSAID-related risks throughout the entire GI tract and identification of the most appropriate risk-reduction strategies. In an interview, he said that for high-risk patients, the combination of a PPI to protect the upper GI tract and a coxib to protect the lower GI tract might prove to be the best strategy. Limited preliminary data have suggested a superior safety profile for coxibs, such as celecoxib (Celebrex, Pfizer) than for NSAIDs, he commented. Other puzzle pieces needing definition, he suggested, include confirmation of the identified trends in non-Spanish populations. He concluded, “A need exists for standardized measures of safety that reflect adverse events in the entire GI tract. That would provide a comprehensive picture for the clinician.” References 1. Singh G, Ramey DR, Morfeld D, et al. Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis: A prospective observational cohort study. Arch Intern Med 1996;156:1530–1536. 2. Hirschowitz BI, Lanas A. Intractable upper gastrointestinal ulceration due to aspirin in patients who have undergone surgery for peptic ulcer. Gastroenterology 1998;114(5):883–892. 3. Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. Am J Gastroenterol 2005;100:1685–1693. continued on next page Vol. 34 No. 1 • January 2009 • P&T® 35
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