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Interaction of Helicobacter pylori infection and low-dose aspirin in the upper gastrointestinal tract: Implications for clinical practice
Low-dose aspirin has been shown to increase the risk of upper gastrointestinal tract injury. Risk factors in upper gastrointestinal complications in low-dose aspirin users are less well defined than in other NSAID users, and there are enough intrinsic differences in the two agents to discuss them separately. In particularly, the role of Helicobacter pylori and the benefit of its eradication in decreasing the risk of upper gastrointestinal tract injury in low-dose ASA users remains controversial. Various consensus groups have recommended H. pylori testing and eradication in low-dose ASA users with a prior history of peptic ulcer or ulcer bleeding. The basis of this recommendation is derived from a limited, albeit expanding evidence on the role of H. pylori in upper gastrointestinal tract injury in low-dose ASA users and on the effectiveness of H. pylori eradication in reducing the risk of complications such as rebleeding in high-risk patients.
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Aspirin: The balance between benefits and harms
Acetylsalicylic acid (aspirin) has been in the market for more than 110 years since Felix Hoffman modified the sodium salt of salicylic acid by acetylation at the end of the XIX century. Aspirin (ASA) was and is taken for the relief of pain, fever and inflammation but now it is the drug of reference for the prevention of cardiovascular events. Much more recently, there is accumulating evidence that ASA has chemopreventive effects in the prevention of several gastrointestinal tumours including colon cancer and adenocarcinoma of the oesophagus. Despite the considerable benefits of the use of this compound, the success of it has been tempered by the occurrence of side effects, many of them also located in the gastrointestinal tract, which seem related to the dose of drug and duration of therapy.
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Aims & Scope/ Editorial Board
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Efficacy and gastrointestinal risk of aspirin used for the treatment of pain and cold
Aims: To analyse major sources of evidence-based information on the efficacy and gastrointestinal tolerability of aspirin, used short-term, in over-the-counter (OTC) doses, to relieve acute pain and cold symptoms, including associated feverishness.Methods: Evidence was largely collected from published meta-analyses and systematic reviews that focused on randomised, controlled, double-blind clinical trials, in which aspirin was compared to placebo and, in some cases also, to active comparators such as OTC doses of paracetamol or ibuprofen.Results: Across a large number of comparisons, aspirin was superior to placebo in treating pain, cold or fever. Efficacy was essentially similar to that of comparators used in equivalent doses. There was no serious GI adverse event attributed to ASA in any study, but mild-to-moderate dyspepsia in small percentages of cases was commonly reported.Conclusion: OTC aspirin is safe and effective. Safety concerns should not limit brief use to relieve acute pain, cold or fever.
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Aspirin and the prevention of colorectal cancer
A large body of evidence from basic science, epidemiologic observations and population-based studies demonstrates that aspirin, as well as other non-steroidal anti-inflammatory drugs, has a chemopreventive effect on several cancer types and, more specifically, in CRC. This protective effect includes prevention of adenoma recurrence and reduction of CRC incidence and mortality. Although the protective effect appears to depend on the dose and the drug, the most important factor is the duration of exposure. However, the lowest effective dose, treatment duration, specific target populations, and effects on survival have not been defined yet. More important, data on the risk–benefit profile for cancer prevention are insufficient and, accordingly, no definitive recommendation can be made at present.In this article, besides reviewing current knowledge of the mechanisms involved in aspirin-based CRC chemoprevention, we will be focused on randomized controlled studies assessing its efficacy in high-, moderate- and average-risk populations.
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Role of ASA in the primary and secondary prevention of cardiovascular events
Cardiovascular disease, which includes coronary heart disease, cerebrovascular disease and peripheral artery disease, is the leading cause of death in developed countries. Evidence from basic research, clinical investigations, observational epidemiologic studies and randomized clinical trials has provided strong support for the benefits of aspirin in decreasing the risk of cardiovascular events in a wide range of pathologies in secondary prevention. Data in primary prevention have far more uncertainties. An overview for the evidence supporting the efficacy of aspirin in primary and secondary prevention of cardiovascular disease is discussed, including the relative and absolute benefit and the risks of side effects. Finally, future developments in the field directed towards individualized treatment strategies and novel antiplatelet agents are examined.
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Prevention of damage induced by aspirin in the GI tract
Low-dose aspirin (325 mg or less) alone and in combination with other antiplatelet agents is widely used for the management of cardiovascular disease. Although the risk with low-dose aspirin alone is less than Nonsteroidal anti-inflammatory drugs (NSAIDs), given widespread use, aspirin related toxicity has become a substantial health care problem due to acute and chronic GI bleeding. A variety of strategies are currently available to minimize the risk of developing upper GI side effects of aspirin. Agents that have efficacy include oral prostaglandin analogues, H2 receptor antagonists and proton pump inhibitors. PPIs appear to be the most effective strategy, with the least side effects and the convenience of once daily dosing. The substitution of another antiplatelet agent such as clopidogrel for aspirin alone does not appear to provide a safer alternative to low-dose aspirin for patients at GI risk. Small bowel injury can occur with aspirin and can be assessed with capsule endoscopy; however, no strategy is known to reduce this potential toxicity in clinical practice.
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Risk factors for gastrointestinal bleeding associated with low-dose aspirin
Low-dose aspirin use is associated with an increased risk for gastrointestinal ulceration and bleeding. At-risk low-dose aspirin users are therefore recommended to take proton-pump inhibitors. However, it is poorly understood which aspirin users are at risk to develop such complications. It is assumed that the known risk factors for NSAID-induced upper gastrointestinal events also apply to low-dose aspirin users. The conventional risk factors for upper gastrointestinal complications associated with aspirin therapy include: (1) a history of peptic ulcer disease or gastrointestinal bleeding, (2) older age, (3) concomitant use of NSAIDs, including coxibs, (4) concomitant use of anticoagulants or other platelet aggregation inhibitors, (5) the presence of severe co-morbidities, and (6) high aspirin dose. In patients with a history of peptic ulcer disease, Helicobacter pylori infection should be assessed and treated. This review focuses on the evidence for upper gastrointestinal risk factors in aspirin users.
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Balancing the risk and benefits of low-dose aspirin in clinical practice
Antiplatelet agents are widely used in primary and secondary prevention of cardiovascular events. The scientific evidence has provided strong support for the benefits of aspirin in decreasing the risk of cardiovascular events in a wide range of pathologies. The relatively rare occurrence of major bleeding complications should not be underestimated, mainly due to its high morbi-mortality. The assessment of both gastrointestinal risk and cardiovascular benefits of low-dose aspirin for any individual patient may be difficult in clinical practice.In this review, we summarize the evidence supporting the efficacy of aspirin and the risks of side effects due to hemorrhagic complications. This article proposes a unifying framework for application to help the clinician in the decision making process of individuals who have different risk of cardiovascular and bleeding events with different examples. Finally, new developments in the field directed towards individualized risk assessment strategies are described.
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Gastrointestinal lesions and complications of low-dose aspirin in the gastrointestinal tract
Low dose aspirin (ASA) use has been associated with a wide range of adverse side effects in the upper gastrointestinal (GI) tract, which range from troublesome symptoms without mucosal lesions to more serious toxicity, including ulcers, GI bleeding, perforation and even death. Upper GI symptoms in low dose ASA users are common but often careless or misinterpreted and they are not always related to the presence of mucosal injury. Usually, low dose ASA related ulcers are reasonably small and asymptomatic, and probably heal over a period of weeks to a few months. But, the real clinical problem occurs when the ulcer results in a GI complication (mostly bleeding). The estimated average excess risk of symptomatic or complicated ulcer related to low dose ASA is five cases per 1000 ASA users per year. Death is the worst outcome of GI complications in low dose ASA users, but data about this aspect are scarce. Current evidence indicates that low dose ASA can damage the lower GI tract also, but the real size of the problem is still unknown.
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Aspirin and NSAIDs; benefits and harms for the gut
Despite modern advances in cancer research, screening and treatment options, gastrointestinal tumours remain a leading cause of death worldwide. Both oesophageal and colorectal malignancies carry high rates of morbidity and mortality, presenting a challenge to clinicians in search of effective management strategies. In recent years, the increasing burden of disease has led to a paradigm shift in our approach from treatment to prevention. Among several agents postulated as having a chemopreventive effect on the gastrointestinal tract, aspirin has been most widely studied and has gained universal acknowledgement. There is an expanding evidence base for aspirin as a key mediator in the prevention of dysplastic change in Barrett’s oesophagus and colorectal adenomas. Its cardioprotective effects also impact positively on the patient population in question, many of whom have ischaemic vascular disease.The major side effects of aspirin have been well-characterised and may cause significant morbidity and mortality in their own right. Complications such as peptic ulceration, upper gastrointestinal bleeding and haemorrhagic stroke pose serious threats to the routine administration of aspirin and hence a balance between the risks and benefits must be struck if chemoprevention is to be effective on a large scale. In this review, we address the current evidence base for aspirin use in gastrointestinal oncology, as well as several key questions surrounding its safety, cost effectiveness and optimal dose.
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