NSAID-induced gastrointestinal damage: current clinical management and recommendations for prevention

Gastrointestinal toxicity is a common adverse effect of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and patients at risk should receive prevention therapies. Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) are safer to the gastrointestinal tract than traditional NSAIDs. Current prevention strategies in patients who need NSAIDs should also take into account the presence of cardiovascular risk factors, as coxibs and probably most traditional NSAIDs increase the incidence of serious cardiovascular events. Patients without risk factors should be treated with traditional NSAIDs, whereas patients at risk may receive cotherapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib alone. However, patients with a previous bleeding ulcer should receive the combination of a coxib plus a PPI, and Helicobacter pylori should be tested for and treated if present. Coxib and NSAID therapy should be prescribed with caution in patients with increased cardiovascular risk and should be prescribed at the lowest possible dose and for the shortest period of time. These patients will probably be treated with low-dose aspirin or other antiplatelet agents, which puts them at increased risk of upper gastrointestinal complications. The risk of gastrointestinal toxicity with combined therapy of aspirin and coxib may be lower than that with traditional NSAIDs plus aspirin, but all these patients may benefit from PPI cotherapy. When the lower gastrointestinal tract is of concern, coxib instead of NSAID therapy should be considered. Coxib therapy has better gastrointestinal tolerance than traditional NSAIDs and PPI therapy is effective both in the treatment and prevention of NSAID-induced dyspepsia and should be considered in patients who develop dyspepsia during NSAID or coxib therapy.     

Should we eradicate Helicobacter pylori infection in patients receiving nonsteroidal anti-inflammatory drugs or low-dose aspirin?

Whether Helicobacter pylori infection alters the risk of ulcer disease in patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is one of the most controversial topics in peptic ulcer research. This is an important management issue, particularly in countries where peptic ulcer disease is common and the prevalence of H. pylori infection is high. Current evidence shows that H. pylori infection increases the ulcer risk associated with NSAIDs or low-dose aspirin. Eradication of H. pylori reduces the subsequent risk of endoscopic and complicated ulcers in patients who are about to start long-term NSAIDs. Among patients with H. pylori infection and a history of ulcer bleeding who continue to use low-dose aspirin, 1 week of eradication therapy prevents recurrent ulcer bleeding. Failure of eradication and concomitant use of NSAIDs, however, account for most cases of recurrent bleeding with low-dose aspirin. The apparent protective effect of H. pylori in long-term NSAIDs users reported in some studies was actually the weeding out of susceptible patients who were intolerant to NSAIDs. There is no convincing evidence that eradication of H. pylori has any clinically important adverse effect on the healing and prevention of ulcers in NSAIDs users.     

Prevention and treatment of NSAID-induced gastroduodenal injury

Opinion statement NSAIDs increase the risk of gastrointestinal (GI) complications. Those at risk should be considered for alternatives to NSAID therapy, modifications of risk factors, and prevention strategies with co-therapy with gastroprotective agents (proton-pump inhibitors [PPIs] or misoprostol) or COX-2 selective inhibitors (coxibs). Since coxibs, and probably other nonselective NSAIDs, may increase the risk of cardiovascular events, prevention strategies must take into account both GI and cardiovascular risk factors. All NSAIDs and coxibs should be prescribed at the lowest possible dose and for the shortest period of time. In patients with GI risk factors but no cardiovascular risk, coxibs or NSAIDs plus PPI or misoprostol are valid options. Patients with a history of ulcer bleeding should receive coxib plus PPI therapy and should be tested and treated for Helicobacter pylori infection. Most patients with increased cardiovascular risk will be treated with antiplatelet agents. It is not known whether co-therapy with low-dose aspirin will reduce the incidence of cardiovascular events, but it will further increase GI risk. It is currently unclear whether the risk of developing upper GI events with coxib plus aspirin is lower than it is with NSAIDs plus aspirin. However, all these patients should benefit from PPI co-therapy. Helicobacter pylori eradication should be considered as an additional therapeutic option when we want to further reduce the GI risk in specific patients. When the lower GI tract is of concern, coxib rather than NSAID therapy should be considered as the first option. Coxib therapy has better GI tolerance than NSAIDs, but patients with peptic ulcers or dyspepsia during NSAID/coxib treatment need PPI co-therapy.     

The David Y. Graham lecture: use of nonsteroidal antiinflammatory drugs in a COX-2 restricted environment

Recent evidence suggests that both cyclooxygenase-2 (COX-2) inhibitors and nonselective NSAIDs, with the possible exception of naproxen, increase cardiovascular (CV) hazard. Clinicians should assess not only patients' GI risk but also their CV risk before prescribing these drugs. Patients with low CV risk can be managed according to their GI risk—low-risk patients (without risk factors) receive nonselective NSAIDs, medium risk patients (1–2 risk factors) receive COX-2 inhibitors or nonselective NSAIDs plus a proton pump inhibitor (PPI) or misoprostol, whereas high-risk patients (multiple risk factors, previous ulcer complications, or concomitant anticoagulants) receive a COX-2 inhibitor plus a PPI or misoprostol. Among patients with high CV risk ( e.g. , prior cardiothrombotic events) who require NSAIDs, naproxen is preferred. These patients should receive a prophylactic PPI or misoprostol because the risk of ulcer bleeding is substantially increased with concomitant use of naproxen and low-dose aspirin. Substitution of clopidogrel for aspirin is not recommended in patients at risk for upper GI bleeding who require antiplatelet therapy. Patients with high GI and high CV risk should avoid NSAIDs and COX-2 inhibitors. If antiinflammatory analgesics are required, the choice of therapy depends on the relative importance of GI and CV risks of individual patients. Combination of naproxen, low-dose aspirin, and a PPI or misoprostol is recommended if CV risk is the major concern ( e.g. , recent myocardial infarction). In contrast, combination of low-dose COX-2 inhibitor, low-dose aspirin, and a PPI or misoprostol is preferred if GI risk outweighs CV risk ( e.g. , recent ulcer bleeding and stable CV disease).     

NSAID‐induced gastrointestinal damage: Current clinical management and recommendations for prevention

Gastrointestinal toxicity is a common adverse effect of traditional non‐steroidal anti‐inflammatory drugs (NSAIDs) and patients at risk should receive prevention therapies. Selective cyclooxygenase‐2 (COX‐2) inhibitors (coxibs) are safer to the gastrointestinal tract than traditional NSAIDs. Current prevention strategies in patients who need NSAIDs should also take into account the presence of cardiovascular risk factors, as coxibs and probably most traditional NSAIDs increase the incidence of serious cardiovascular events. Patients without risk factors should be treated with traditional NSAIDs, whereas patients at risk may receive cotherapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib alone. However, patients with a previous bleeding ulcer should receive the combination of a coxib plus a PPI, and Helicobacter pylori should be tested for and treated if present. Coxib and NSAID therapy should be prescribed with caution in patients with increased cardiovascular risk and should be prescribed at the lowest possible dose and for the shortest period of time. These patients will probably be treated with low‐dose aspirin or other antiplatelet agents, which puts them at increased risk of upper gastrointestinal complications. The risk of gastrointestinal toxicity with combined therapy of aspirin and coxib may be lower than that with traditional NSAIDs plus aspirin, but all these patients may benefit from PPI cotherapy. When the lower gastrointestinal tract is of concern, coxib instead of NSAID therapy should be considered. Coxib therapy has better gastrointestinal tolerance than traditional NSAIDs and PPI therapy is effective both in the treatment and prevention of NSAID‐induced dyspepsia and should be considered in patients who develop dyspepsia during NSAID or coxib therapy.     

Helicobacter pylori and nonsteroidal anti-inflammatory drugs.

The complex interaction between H. pylori and NSAIDs implies that it is over simplistic to conclude that their relationship is independent, synergistic, or antagonistic without considering the influence of other factors. Factors such as previous exposure to NSAIDs, a history of ulcer complication, concurrent use of acid-suppressant therapy, and the difference between NSAIDs and low-dose aspirin all affect the outcome. Several recommendations can be made with regard to the indications of H. pylori eradication for patients requiring NSAIDs. First, patients taking NSAIDs who have ulcers or previous ulcer disease should be tested for the bacterium, and it should be eradicated if present because it is impossible to determine whether the ulcers are caused by H. pylori or NSAIDs or both. Antiulcer drugs should be prescribed to prevent ulcer recurrence for patients who continue to require NSAIDs. Although the efficacy of omeprazole is enhanced by H. pylori infection, it is not justified to leave a pathogen in the stomach in exchange for a modest therapeutic gain. Second, for patients who take low-dose aspirin, eradication of H. pylori substantially reduces the risk of ulcer bleeding. It is advisable that patients taking low-dose aspirin who are at risk of ulcer bleeding should be tested for H. pylori and treated for it if the infection is found. Third, for patients who are about to start NSAIDs, screen-and-treat H. pylori has the potential of reducing the ulcer risk at an affordable incremental cost. It might be argued that any interaction between H. pylori and NSAIDs would become irrelevant in the era of COX-2-selective NSAIDs. Even among patients who are receiving a COX-2-selective NSAID, however, a large-scale study showed that the ulcer risk is significantly higher in H. pylori-positive patients than in uninfected patients. This finding suggests that the relative importance of H. pylori in ulcer development might increase with a reduced toxicity of COX-2-selective NSAIDs. With an increasing use of low-dose aspirin for cardiovascular prophylaxis, the problem of aspirin-related ulcer disease is expected to rise. Given the significant role of H. pylori in the latter condition, screen-and-treat H. pylori might be a useful strategy for the prevention of ulcer complications in high-risk patients receiving low-dose aspirin in the future.     

Helicobacter pylori, NSAIDs and gastrointestinal haemorrhage.

Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) cause the majority of bleeding ulcers. Whether the presence of H. pylori infection would affect the risk of ulcers in patients taking NSAIDs is important for both theoretical and practical reasons. However, the results have been so conflicting that there is no consensus on the management of patients requiring NSAIDs who are infected with H. pylori. The controversy is largely due to the variable study design and marked heterogeneity of the study population. Studying the interaction between H. pylori and NSAIDs without considering these factors often leads to erroneous conclusions. Current evidence suggests that H. pylori contributes to an increased ulcer risk for patients who are about to start NSAID treatment, whereas NSAIDs probably account for the majority of ulcer disease in patients who are already taking long-term NSAIDs. In the light of the reduced gastric toxicity of COX-2 inhibitors, the relative importance of H. pylori in the pathogenesis of ulcers is expected to increase. Furthermore, recent evidence suggests that H. pylori contributes to ulcer bleeding associated with low-dose aspirin. Among H. pylori-positive patients with a history of ulcer bleeding who are taking low-dose aspirin, the eradication of H. pylori has been shown to be comparable to omeprazole in preventing recurrent bleeding.     

Risk and preventive factors of low-dose aspirin-induced gastroduodenal injuries: a comprehensive review

The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1β (IL-1β)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1β and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA.     

Avances en patología gastrointestinal relacionada con el tratamiento con antiinflamatorios no esteroideos y antiagregantes plaquetarios

The most important and recent advance reported in the field of the non-steroidal antiinflammatory drug (NSAID)-associated gastrointestinal (GI) lesions is the CONDOR study. This study shows that treatment with celecoxib 200 mg/12 hours is associated with a lower frequency of clinically significant adverse effects throughout the GI tract when compared with treatment with diclofenac 75 mg/12 hours + omeprazole 20 mg/day in at-risk patients with osteoarthritis or rheumatoid arthritis. Other studies of interest report that most arthritis patients requiring NSAIDs are at increased GI and cardiovascular risk and that more than 50% do not receive appropriate therapy based on current recommendations. Recent epidemiological studies confirm that aspirin use, alone or associated with other antiplatelet agents, is associated with increased risk of GI bleeding from either the upper or the lower GI tract, and that proton pump inhibitors (PPIs) reduce the risk of upper GI bleeding. The most recent data also question the negative interaction between PPI and clopidogrel, but the data are still generally of low quality. A notable new compound is cobiprostone, a local chloride channel activator. When combined with NSAIDs, this agent reduces the occurrence of gastric lesions. Another new agent that combines aspirin with phosphatidylcholine is associated with a lower degree of gastroduodenal mucosal damage than aspirin and has identical antiplatelet effect to aspirin alone.     

Secondary and primary prophylaxis of gastropathy associated with nonsteroidal antiinflammatory drugs or low-dose-aspirin: a review based on four clinical scenarios

Based on current references four clinical scenarios were discussed and different management strategies were compared for secondary and primary prophylaxis of ulcer or peptic ulcer bleeding under continuous therapy with non-steroidal antiinflammatory drugs (NSAID) or low-dose-aspirin, for H.pylori-positive and H.pylori-negative patients. Used as secondary prophylaxis eradication alone is insufficient in preventing recurrent peptic ulcer or recurrent ulcer bleeding for H.pylori-positive patients who continue to take unselective NSAIDs. Maintenance therapy with PPIs or switching from nonselective NSAID to COX-2-inhibitors is required after eradication of H.pylori or primary H.pylori-negative patients. Further evaluation is needed of what kind of secondary prophylaxis - maintenance therapy with PPI or switching to COX-2-inhibitor - is more (cost-)effective. It is sufficient to use eradication of H.pylori alone as secondary prophylaxis in preventing recurrent peptic ulcer or recurrent ulcer bleeding for H.pylori-positive patients, who continue to take low-dose-aspirin. Maintenance therapy with PPI is not generally required. However it can be considered for patients with increased risk for gastrointestinal complications (previous history of peptic ulcer, age over 65 years, concomitant use of corticosteroids, anticoagulants or individual NSAID with higher risk for gastrointestinal complications, serious cardiovascular disease). Switching from low-dose-aspirin to clopidogrel is not required. Used as primary prophylaxis in preventing peptic ulcer or ulcer bleeding before starting long-term therapy with NSAIDs, COX-2-inhibitors or unselective NSAIDs concomitant with PPIs are recommended for patients with increased risk for gastrointestinal complications. Patients starting long-term therapy with unselective NSAIDs should be screened for H.pylori and eradicated. There are no valid data supporting screening for H.pylori and eradication for patients starting long-term therapy with low-dose-aspirin. Further studies are needed to evaluate a possible benefit for patients with increased risk for gastrointestinal complications.     

Specifics of Helicobacter pylori infection/NSAID effects in the elderly

The prevalence of Helicobacter pylori (HP) infection increases with age worldwide. Unlike in younger patients, the presentation of peptic disease in the elderly population is subtle and atypical, and thus leads to a delay of diagnosis. Due to comorbidities and advanced age, it results in increased complications, morbidity and mortality. Bleeding and perforation are frequent complications and therefore peptic ulcer in adult patients represents a serious disease. The relationship between the infection caused by HP and the use of non-steroidal anti-inflammatory drugs (NSAID) in the pathogenesis of peptic ulcer disease is still controversial. However these two factors, independently or in synergy, represent the principal cause of peptic ulcer development in the adult population. In patients diagnosed with peptic ulcer caused by HP, more than half take medications containing aminosalicylic acid. Helicobacter pylori infection in elderly NSAID users is associated with an increased ulcer incidence, but not with an increased prevalence of upper digestive tract bleeding. Helicobacter pylori and NSAID consumption are independent and unrelated risk factors for upper gastrointestinal tract bleeding. Eradication of HP is recommended before the initiation of a long-term aspirin administration in elderly patients. Low aspirin dosages are associated with a high risk of ulcer bleeding. The risk of upper gastrointestinal bleeding in elderly patients is significantly higher in the cases of acute abuse of NSAIDs relative to its chronic use. The simultaneous use of NSAID or aspirin and selective serotonin reuptake inhibitors--antidepressants, increases the risk of upper gastrointestinal bleeding. Peptic ulcer disease in the adult population, if combined with old age, presence of serious and/or life- threatening diseases, as well as repeated ulcer bleedings, shows a high mortality rate.     

NSAIDs-induced gastrointestinal damage. Review

Non-steroidal anti-inflammatory drugs (NSAIDs), along with analgesics, are the most widely prescribed medication in the world. However, NSAIDs cause numerous side effects, being the gastrointestinal (GI) events the most common ones with an increase of risk of serious GI complications between 2.5- and 5-fold, as compared with individuals not taking NSAIDs. Factors that increase the risk for serious events in NSAID-using patients include a history of ulcer or ulcer complications, advanced age (=or>65 years), the use of high-dose NSAIDs, more than one NSAID, anticoagulants or corticosteroid therapy. If NSAID therapy is required, we must balance GI and cardiovascular risk and the therapy should be prescribed at the lowest possible dose and for the shortest period of time. The use of NSAID without gastroprotective co-therapy is considered appropriate in patients<65 years, not taking aspirin and having no GI history. In patients with GI risk factors, but no cardiovascular risk, coxibs or NSAIDs plus proton pump inhibitor (PPI) or misoprostol are valid options. Patients with a history of ulcer bleeding should receive coxib plus PPI therapy and should be tested and treated for Helicobacter pylori infection. Coxib therapy has better GI tolerance than traditional NSAIDs and PPI therapy is effective both in treatment and prevention of NSAID-induced dyspepsia and should be considered in patients who develop dyspepsia during NSAID or coxib therapy.     

Role of Helicobacter pylori eradication in aspirin or non-steroidal anti-inflammatory drug users

Helicobacter pylori(H pylori) infection and the use of non steroidal anti-inflammatory drugs (NSAIDs) including aspirin at any dosage and formulation represent well-established risk factors for the development of uncomplicated and complicated peptic ulcer disease accounting for the majority of such cases. Although the interaction between H pylori and NSAID/aspirin use in the same individuals was questioned in some epidemiological studies, it has now become widely accepted that they are at least independent risk factors for peptic ulcer disease. According to data from randomized intervention trials, naive NSAID users certainly benefit from testing for H pylori infection and, if positive, H pylori eradication therapy prior to the initiation of NSAID. A similar strategy is also suggested for naive aspirin users, although the efficacy of such an approach has not been evaluated yet. Strong data also support that chronic aspirin users with a recent ulcer complication should be tested for H pylori infection and, if positive, receive H pylori eradication therapy after ulcer healing, while they appear to benefit from additional long-term therapy with a proton pump inhibitor (PPI). A similar approach is often recommended to chronic aspirin users at a high risk of ulcer complication. H pylori eradication alone does not efficiently protect chronic NSAID users with a recent ulcer complication or those at a high-risk, who certainly should be treated with long-term PPI therapy, but H pylori eradication may be additionally offered even in this setting. In contrast, testing for H pylori or PPI therapy is not recommended for chronic NSAID/aspirin users with no ulcer complications or those at a low risk of complications.     

Proton pump inhibitor co-therapy with nonsteroidal anti-inflammatory drugs--nice or necessary?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory, analgesic, and anti-pyretic effects, whereas low-dose aspirin (also an NSAID) is used for cardiovascular prophylaxis. The main concern limiting use of these drugs is their gastrointestinal (GI) toxicity. GI side effects include ulcers (found at endoscopy in 15%-30% of patients using NSAIDs regularly), complications such as upper GI bleeding (annual incidence of 1.0%-1.5%), and development of upper GI symptoms such as dyspepsia (occurring in up to 60% of patients taking NSAIDs). Histamine-2 receptor antagonists are not effective at preventing NSAID-induced gastric ulcers when used at standard doses, although they can decrease upper GI symptoms. Misoprostol effectively decreases NSAID-induced ulcers and GI complications but is used infrequently in the United States-perhaps because of issues of compliance (multiple daily doses) and side effects (eg, diarrhea, dyspepsia). Once-daily proton pump inhibitor (PPI) therapy also decreases the development of NSAID-associated ulcers and recurrent NSAID-related ulcer complications; it also decreases upper GI symptoms in NSAID users. In patients using aspirin, the addition of a cyclooxygenase-2-specific inhibitor appears to significantly increase GI risk to the level of a nonselective NSAID; aspirin plus a nonselective NSAID appears to increase GI risk still higher. Patients taking low-dose aspirin who have risk factors for GI complications (including concomitant nonselective NSAID therapy) should receive medical co-therapy, such as a PPI.     

Epidemiology of acute upper gastrointestinal bleeding

Acute upper gastrointestinal bleeding is an important emergency situation. Population-based epidemiology data are important to get insight in the actual healthcare problem. There are only few recent epidemiological surveys regarding acute upper gastrointestinal bleeding. Several surveys focusing on peptic ulcer disease showed a significant decrease in admission and mortality of peptic ulcer disease. Several more recent epidemiological surveys show a decrease in incidence of all cause upper gastrointestinal bleeding. The incidence of peptic ulcer bleeding remained stable. Peptic ulcer bleeding is the most common cause of upper gastrointestinal bleeding, responsible for about 50% of all cases, followed by oesophagitis and erosive disease. Variceal bleeding is the cause of bleeding in cirrhotic patients in 50-60%. Rebleeding in upper gastrointestinal bleeding occurs in 7-16%, despite endoscopic therapy. Rebleeding is especially high in variceal bleeding and peptic ulcer bleeding. Mortality ranges between 3 and 14% and did not change in the past 10 years. Mortality is increasing with increasing age and is significantly higher in patients who are already admitted in hospital for co-morbidity. Risk factors for peptic ulcer bleeding are NSAIDs use and H. pylori infection. In patients at risk for gastrointestinal bleeding and using NSAIDs, a protective drug was only used in 10%. COX-2 selective inhibitors do cause less gastroduodenal ulcers compared to non-selective NSAIDs, however, more cardiovascular adverse events are reported. H. pylori infection is found in about 50% of peptic ulcer bleeding patients. H. pylori should be tested for in all ulcer patients and eradication should be given.     

Polypharmacy of Osteoarthritis: The Perfect Intestinal Storm

Osteoarthritis is an increasingly prevalent disorder with an incidence rate that rises sharply with age. Unfortunately, the most commonly used medications for providing symptomatic relief, nonsteroidal anti-inflammatory drugs (NSAIDs), can cause significant gastrointestinal (GI) ulceration. There is recent evidence that agents commonly employed to protect the upper GI tract actually increase the incidence and severity of ulceration and bleeding in the lower intestine. Intestinal injury is more difficult to diagnose and treat than upper GI damage, and symptoms correlate poorly with the severity of tissue injury. Moreover, use of low-dose aspirin for cardioprotection (a common co-treatment with the selective cyclooxygenase-2 inhibitors) further augments intestinal damage, particularly when enteric-coated aspirin is used. Thus, by focusing entirely on prevention of NSAID-induced damage to the upper GI tract, physicians may be inadvertently placing their patients at risk of serious, difficult-to-diagnose injury for which there are no proven-effective therapies and are associated with significantly higher rates of morbidity and mortality.     

Should coronary patients chronically taking a low-dose of aspirin receive gastroprotective agents?]

The use of low-dose aspirin (75-300 mg/day) is associated with an increased risk of gastrointestinal bleeding, which is lower than that observed with common NSAIDs. Risk factors for the development of GI bleeding in patients taking low-dose aspirin are not well defined, although patients with a previous history of peptic ulcer, concomitant NSAID use and serious diseases should receive gastroprotection. Among the available drugs, proton pump inhibitors associated, when present, to Helicobacter pylori erradication, have shown the highest efficacy. The best cost-effectiveness treatment is still undefined.     

Peptic ulcer disease today

Over the past few decades, since the introduction of histamine H(2)-receptor antagonists, proton-pump inhibitors, cyclo-oxygenase-2-selective anti-inflammatory drugs (coxibs), and eradication of Helicobacter pylori infection, the incidence of peptic ulcer disease and ulcer complications has decreased. There has, however, been an increase in ulcer bleeding, especially in elderly patients. At present, there are several management issues that need to be solved: how to manage H. pylori infection when eradication failure rates are high; how best to prevent ulcers developing and recurring in nonsteroidal anti-inflammatory drug (NSAID) and aspirin users; and how to treat non-NSAID, non-H. pylori-associated peptic ulcers. Looking for H. pylori infection, the overt or surreptitious use of NSAIDs and/or aspirin, and the possibility of an acid hypersecretory state are important diagnostic considerations that determine the therapeutic approach. Combined treatment with antisecretory therapy and antibiotics for 1-2 weeks is the first-line choice for H. pylori eradication therapy. For patients at risk of developing an ulcer or ulcer complications, it is important to choose carefully which anti-inflammatory drugs, nonselective NSAIDs or coxibs to use, based on a risk assessment of the patient, especially if the high-risk patient also requires aspirin. Testing for and eradicating H. pylori infection in patients is recommended before starting NSAID therapy, and for those currently taking NSAIDs, when there is a history of ulcers or ulcer complications. Understanding the pathophysiology and best treatment strategies for non-NSAID, non-H. pylori-associated peptic ulcers presents a challenge.     

Gastrointestinal bleeding after percutaneous coronary intervention

Percutaneous coronary intervention (PCI) is now performed in a wide range of patients with coronary artery disease. Complications of PCI include in-stent re-stenosis and in-stent thrombosis. According to the recent 2005 guidelines of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions, dual antiplatelet therapy with low-dose aspirin and thienopyridine derivatives such as ticlopidine and clopidogrel should be used in patients who have undergone PCI. A serious complication of dual antiplatelet therapy is bleeding, most of which arise from the gastrointestinal (GI) tract. In this article we review published studies about GI bleeding in patients who have undergone PCI. The prevalence of GI bleeding in patients who are administered dual antiplatelet therapy following PCI is approximately 2%, and GI bleeding after PCI is associated with increased morbidity, mortality, duration of hospitalization and cost. Advanced age, a history of peptic ulcer disease, co-administration of non-steroidal anti-inflammatory drugs, co-administration of anticoagulants, and physiological stress are considered to be the major risk factors for GI bleeding in patients undergoing antiplatelet therapy following PCI. Recent clinical and experimental studies indicate that administration of low-dose aspirin may also increase the risk of adverse events in the small intestine. Although some prophylactic strategies such as proton-pump inhibitor, H? receptor antagonist and eradication of Helicobacter pylori are proposed, there are few randomized controlled trials assessing the best strategy for the prevention of GI bleeding after PCI. Further extensive studies are required to ascertain the beneficial effect of prophylactic agents for dual antiplatelet therapy following PCI.     

Should we eradicate Helicobacter pylori infection in patients receiving nonsteroidal anti‐inflammatory drugs or low‐dose aspirin?

Whether Helicobacter pylori infection alters the risk of ulcer disease in patients receiving nonsteroidal anti‐inflammatory drugs (NSAIDs) or low‐dose aspirin is one of the most controversial topics in peptic ulcer research. This is an important management issue, particularly in countries where peptic ulcer disease is common and the prevalence of H. pylori infection is high. Current evidence shows that H. pylori infection increases the ulcer risk associated with NSAIDs or low‐dose aspirin. Eradication of H. pylori reduces the subsequent risk of endoscopic and complicated ulcers in patients who are about to start long‐term NSAIDs. Among patients with H. pylori infection and a history of ulcer bleeding who continue to use low‐dose aspirin, 1 week of eradication therapy prevents recurrent ulcer bleeding. Failure of eradication and concomitant use of NSAIDs, however, account for most cases of recurrent bleeding with low‐dose aspirin. The apparent protective effect of H. pylori in long‐term NSAIDs users reported in some studies was actually the weeding out of susceptible patients who were intolerant to NSAIDs. There is no convincing evidence that eradication of H. pylori has any clinically important adverse effect on the healing and prevention of ulcers in NSAIDs users.