Aspirin: The balance between benefits and harms

Aspirin: The balance between benefits and harms

Best Practice & Research Clinical Gastroenterology 26 (2012) 97–99 Contents lists available at SciVerse ScienceDirect Best Practice & Research Clini...

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Best Practice & Research Clinical Gastroenterology 26 (2012) 97–99

Contents lists available at SciVerse ScienceDirect

Best Practice & Research Clinical Gastroenterology

Preface

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. In this issue we review most aspects related to both benefits and harms associated with the use of ASA in different clinical scenarios. Epidemiological studies report that ASA and other NSAIDs are associated with a 4-fold increase in the risk of upper gastrointestinal bleeding. Here, Prof. Denis McCarthy reviews the evidence on the efficacy and gastrointestinal tolerability of ASA to relieve acute pain and cold symptoms, mainly in short-term and OTC use. The relief of pain, fever, cold and inflammation was the first indication of this drug when marketed more than hundred years ago, and it still is being used for these same indications by millions of people worldwide. The evidence was collected from published meta-analyses and systematic reviews focused on randomized, controlled, double-blind clinical trials. He concludes that ASA was superior to placebo in treating pain, cold or fever and similar to that of comparators used in equivalent doses. Short-term use (in most cases single dose) was associated with no serious GI adverse event attributed to ASA in any study, but mild-tomoderate dyspepsia in small percentages of cases was commonly reported [1]. Today, however, the main indication of aspirin is for the prevention of CV events. Rubén CasadoArroyo, Fatih Bayrak, & Pedro Brugada review these aspects including coronary heart disease, cerebrovascular disease and peripheral artery disease [2]. They report that the 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 secondary prevention. However, data in primary prevention is uncertain. They discuss evidence supporting the efficacy of low-dose ASA in primary and secondary prevention of cardiovascular disease including the relative and absolute benefit and the risks of side effects. Finally, they comment on individualized treatment strategies and novel antiplatelet agents. Bleeding is the main potentially serious side effect of both cardio and OTC ASA use. Gastrointestinal bleeding is a major threat; Carlos Sostres and Carla Gargallo from the University Hospital in Zaragoza, a centre that has provided seminal information on this issue over the past two decades, review this area. In their review the authors point out that the range of adverse events with ASA goes from troublesome symptoms without mucosal lesions to more serious toxicity, including ulcers, GI bleeding, perforation and even death. They also point out that ASA can damage the lower GI tract. They report data on death linked to GI bleeding and ASA use, and outline that ulcer bleeding linked deaths are 1521-6918/$ – see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.bpg.2012.03.006

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Preface / Best Practice & Research Clinical Gastroenterology 26 (2012) 97–99

because of non-ulcer bleeding causes and are associated with non-GI risk factors such as multi-organ failure, cardiopulmonary conditions or terminal malignancy [3]. In order to provide the best care and to design appropriate therapeutic strategies, it is important to identify patients that are at special risk of developing complications. Valkhoff et al [4] has revised here the available evidence concerning this important issue and shows that today, still it is poorly understood which aspirin users are at risk to develop such complications, and that most assume that the well known risk factors for NSAID-induced upper gastrointestinal events also apply to low-dose aspirin users. These factors include history of peptic ulcer disease, older age, concomitant use of NSAIDs, including coxibs, concomitant use of anticoagulants or other antiplatelet agents, and the presence of severe co-morbidities. They point out those patients with a history of peptic ulcer disease, Helicobacter pylori infection should be assessed and treated. The role of H. Pylori infection in patients who take aspirin is precisely one major issue for discussion. One world expert in the field write here one article focused exclusively on this issue. Francis Chan and his colleague En-ling Leung Ki [5] revise the role of H. pylori and the benefit of its eradication in decreasing the risk of upper gastrointestinal tract injury in low-dose ASA users. They favour this option although recognize that 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. GI side effects associated with ASA use can be prevented, at least those from the upper GI tract, with currently available anti-ulcer drugs. Professor James Scheiman reviews the variety of strategies currently available to minimize the risk of developing upper-GI side effects of aspirin. He points out that among them, proton pump inhibitors appear to be the most effective strategy, with the least side effects and the convenience of once daily dosing, but no strategy is known to reduce the potential toxicity of ASA to the small bowel injury that can occur in clinical practice [6]. Eventually, one article of this issue try to put all the evidence in terms of CV benefits and GI risk under the appropriate perspective. Casado-Arroyo et al [7] suggest that the assessment of both gastrointestinal risk and cardiovascular benefits of low-dose ASA for any individual patient may be difficult in clinical practice. They summarize the evidence supporting the efficacy of aspirin and the risks of side effects due to hemorrhagic GI complications, and propose 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. The issue and the framework for the balance between benefits and risks could not be completed without revising the evidence of the potential benefits of ASA in the prevention of colon cancer and of cancer of the oesophagus. Based on the review provided by Ferrandez et al [8], it is clear that there is a large body of evidence from basic science, epidemiologic observations and population based studies demonstrating that ASA, as well as other non-steroidal anti-inflammatory drugs, have chemopreventive effects on several cancer types and, more specifically, in colorectal cancer. This protective effect includes prevention of adenoma recurrence and reduction of colon cancer 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. The most recent data suggest that CV doses of ASA could be sufficient to obtain the beneficial effect if used long-term [8]. Prarthana Thiagarajan & Janusz Jankowski provides the most updated knowledge on the potential of ASA in the prevention of adenocarcinoma from Barrett’s oesophagus. The ongoing largest trial in this area, the ASPECT trial, is being conducted in the UK by the senior author. This study will probably provide key information in various aspects and overall on the effects of ASA in the prevention of adenocarcinoma of the oesophagus in patients with Barrett’s oesophagus being treated with proton pump inhibitors and ASA for 10 years [9]. One of the intriguing aspects of the chemopreventive effects of low-dose ASA is the mechanisms of action. Since low-dose ASA will not have a major direct impact on COX-2 inhibition, Annalisa Bruno and colleagues from Patrignani’s group [10] propose in this issue that platelet activation is involved in the early stages of colorectal carcinogenesis in man through the induction of a COX-2-mediated paracrine signalling between stromal cells and epithelial cells within adenomas. I believe that this issue reviews important aspects of ASA, a drug with an enourmous impact in medicine today, since after being in the market for more than 100 years, still it has new potential indications and use in diseases that affect hundreds of million of people worlwide. The reviews are

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conducted by experts in the field who present the most updated information a respectful expert opinion on their respective areas. References [1] McCarthy D. Efficacy and gastrointestinal risk of aspirin used for the treatment of pain and cold. Best Pract Res Clin Gastroenterol 2012;26(2):101–12. [2] Casado-Arroyo R, Bayrak F, Brugada P. Role of ASA in the primary and secondary prevention of cardiovascular events. Best Pract Res Clin Gastroenterol 2012;26(2):113–23. [3] Valkhoff VE, Sturkenboom M, Kuipers EJ. Risk factors for gastrointestinal bleeding associated with low-doseaspirin. Best Pract Res Clin Gastroenterol 2012;26(2):125–40. [4] Sostres C, Gargallo CJ. Gastrointestinal lesions and complications of low-doseaspirin in the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2012;26(2):141–51. [5] Scheiman JM. Prevention of damage induced by aspirin in the GI tract. Best Pract Res Clin Gastroenterol 2012;26(2): 153–62. [6] Ki EL, Chan FKL. Interaction of H. Pylori infection and low-doseaspirin in the upper gastrointestinal tract: implications for clinical practice. Best Pract Res Clin Gastroenterol 2012;26(2):163–72. [7] Casado-Arroyo R, Gargallo CJ, Lanas A. Balancing the risk and benefits of low-doseaspirin in clinical practice. Best Pract Res Clin Gastroenterol 2012;26(2):173–84. [8] Ferrández A, Piazuelo E, Castells A. Aspirin and the prevention of colorectal cáncer. Best Pract Res Clin Gastroenterol 2012; 26(2):185–95. [9] Thiagarajan P, Jankowski JAAspirinNSAIDs. benefits and harms for the gut. Best Pract Res Clin Gastroenterol 2012;26(2): 197–206. [10] Bruno A, Patrignani P. Mechanisms of the antitumoral effects of aspirin in the gastrointestinal tract. Best Pract Res Clin Gastroenterol, in press.

Angel Lanas, MD, Professor Service of Digestive Diseases, University Hospital Lozano Blesa, University of Zaragoza, IIS Aragón, CIBERehd, Zaragoza, Spain E-mail address: [email protected]