ABSTRACT
Title
NSAID-gastropathy: epidemiology and clinical picture
Authors
F. Bazzoli
Division of Gastroenterology & Digestive Endoscopy, Department of Clinical Medicine, University of Bologna, Italy
Division of Gastroenterology & Digestive Endoscopy, Department of Clinical Medicine, University of Bologna, Italy
Abstract
Increasing life expectancy in developed Countries has led to a growing prevalence of arthritic disorders, which has been accompanied by increasing prescriptions for nonsteroidal anti-inflammatory drugs (NSAIDs). These are the most widely used agents for musculoskeletal and arthritic conditions, representing more than 7.7% of all prescriptions in Europe. Although NSAIDs are very effective, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side effects are, the most common and range from dyspeptic symptoms to more serious events such as peptic ulcer with the life-threatening complications of bleeding and perforation.
Upper GI symptoms associated with NSAID use include dyspepsia, heartburn, bloating or cramping, nausea and vomiting in up to 40-50% of patients taking NSAIDs. These symptoms prompt a change in therapy in 10% of patients. Unfortunately, symptoms associated with NSAIDs have little relationship to erosions or ulcerations seen endoscopically, which are often asymptomatic and patients with symptoms often have no identifiable lesions. The first sign of NSAID-induced GI damage in asymptomatic individuals may be a life-threatening complication.
Endoscopic examination of NSAID users can reveal subepithelial hemorrhages, erosions, and ulceration or a combination. Mucosal damage is seen in 30–50% of patients taking NSAIDs, but most lesions are of little clinical significance and disappear or reduce in number with continued use, probably due to mucosal adaptation. Only 15–30% of NSAIDs users have endoscopically confirmed ulcers, with the gastric antrum being the most frequently affected.
GI complications occur in 1–1.5% of patients in the first year of treatment with ns-NSAIDs and, when symptomatic ulcers are included, this rises to 4–5%. The average relative risk of developing a serious GI complication is 3- to 5-fold greater among NSAIDs users than among non-users. Aspirin (ASA) is also associated with both gastric and duodenal ulcers and upper GI complications occur even with the lowest dose of 75 mg/day.Although some studies suggest that the first 2 months of treatment is the period of greatest risk for complications with a relative risk of 4.5%, evidence from both RCTs and observational studies indicate that the risk of GI complications is present with both short-term and long-term use of NSAIDs from the first dose.
The worst GI outcome with NSAIDs is upper GI Bleeding (UGIB), which may result in death. However, mortality data associated with NSAIDs are scarce. Current mortality incidence is estimated at 15.3 deaths per 100,000, among NSAID/aspirin users in a large Spanish study. This is lower than previously quoted, likely due to a decline in the rate of complications over the last 5 to 10 years associated with increasing use of prevention strategies for NSAID-induced GI damage and a decline in the prevalence of H. pylori infection.
Risk factors for UGIB associated with NSAID use have been well defined by several studies. The most important are prior history of complicated ulcer and age. A meta-analysis of case-controlstudies showed synergism for the development of complicated and uncomplicated ulcer between H. pylori infection and NSAIDs.
C. Scarpignato, R.H. Hunt. (2010) Nonsteroidal antiinflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin North Am 39: 433-464.
Straube S, Tramèr MR, Moore RA, Derry S, McQuay HJ (2009). Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. BMC Gastroenterol 2009; 9: 41.
Hunt RH, Bazzoli F (2004). Review article: should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing. Aliment Pharmacol Ther 2004; 19 (Suppl 1): 9-16.
Upper GI symptoms associated with NSAID use include dyspepsia, heartburn, bloating or cramping, nausea and vomiting in up to 40-50% of patients taking NSAIDs. These symptoms prompt a change in therapy in 10% of patients. Unfortunately, symptoms associated with NSAIDs have little relationship to erosions or ulcerations seen endoscopically, which are often asymptomatic and patients with symptoms often have no identifiable lesions. The first sign of NSAID-induced GI damage in asymptomatic individuals may be a life-threatening complication.
Endoscopic examination of NSAID users can reveal subepithelial hemorrhages, erosions, and ulceration or a combination. Mucosal damage is seen in 30–50% of patients taking NSAIDs, but most lesions are of little clinical significance and disappear or reduce in number with continued use, probably due to mucosal adaptation. Only 15–30% of NSAIDs users have endoscopically confirmed ulcers, with the gastric antrum being the most frequently affected.
GI complications occur in 1–1.5% of patients in the first year of treatment with ns-NSAIDs and, when symptomatic ulcers are included, this rises to 4–5%. The average relative risk of developing a serious GI complication is 3- to 5-fold greater among NSAIDs users than among non-users. Aspirin (ASA) is also associated with both gastric and duodenal ulcers and upper GI complications occur even with the lowest dose of 75 mg/day.Although some studies suggest that the first 2 months of treatment is the period of greatest risk for complications with a relative risk of 4.5%, evidence from both RCTs and observational studies indicate that the risk of GI complications is present with both short-term and long-term use of NSAIDs from the first dose.
The worst GI outcome with NSAIDs is upper GI Bleeding (UGIB), which may result in death. However, mortality data associated with NSAIDs are scarce. Current mortality incidence is estimated at 15.3 deaths per 100,000, among NSAID/aspirin users in a large Spanish study. This is lower than previously quoted, likely due to a decline in the rate of complications over the last 5 to 10 years associated with increasing use of prevention strategies for NSAID-induced GI damage and a decline in the prevalence of H. pylori infection.
Risk factors for UGIB associated with NSAID use have been well defined by several studies. The most important are prior history of complicated ulcer and age. A meta-analysis of case-controlstudies showed synergism for the development of complicated and uncomplicated ulcer between H. pylori infection and NSAIDs.
C. Scarpignato, R.H. Hunt. (2010) Nonsteroidal antiinflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin North Am 39: 433-464.
Straube S, Tramèr MR, Moore RA, Derry S, McQuay HJ (2009). Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. BMC Gastroenterol 2009; 9: 41.
Hunt RH, Bazzoli F (2004). Review article: should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing. Aliment Pharmacol Ther 2004; 19 (Suppl 1): 9-16.