Widespread Use Of Aspirin Research Articles

Low-dose aspirin for primary and secondary prevention of cardiovascular events in Denmark 1998\u20132018

Randomised controlled trials have shown a neutral or even unfavourable risk–benefit balance of aspirin for primary prevention of cardiovascular events. Using Danish nationwide registries, we investigated aspirin use and associated risks during the past two decades (1998–2018). We linked individual patient data on repeated aspirin redemptions with registered hospital ICD-10 diagnoses of atherosclerotic cardiovascular disease and bleedings. The prevalence of aspirin use among 1.1 million Danish adults fluctuated over the 20-year study period peaking in 2008 with 8.5% (5.4% primary prevention) and dropping to 5.1% (3.1% primary prevention) in 2018. Aspirin use showed strong age dependency, and 21% of individuals > 80 years were treated with aspirin for primary prevention in 2018. Medication adding to bleeding risk was used concurrently by 21% of all aspirin users in 2018. The incidence of major bleedings were similar with primary and secondary prevention aspirin use and highest in elderly (2 per 100 patient years among individuals > 80 years in 2018). In conclusion, low-dose aspirin use for primary prevention of cardiovascular events remains prevalent. The widespread use of aspirin, especially among older adults, and substantial concomitant use of medications adding to bleeding risk warrant increased focus on discontinuation of inappropriate aspirin use.

Aspirin and colorectal cancer chemoprevention

The role of aspirin in colorectal cancer prevention is currently under intense scrutiny. Low dose Aspirin effectively suppresses the cyclooxygenase-2 enzyme system, which is thought to play an important role in the pathogenesis of colorectal cancer. A number of observational studies and randomized controlled trials have supported a chemoprevention effect. In some instances, regular use of low dose aspirin has provided a nearly 20% reduction in incidence. Compliance and underutilization remain important issues however, as does the incidence of side effects - aspirin is a non-steroidal anti-inflammatory drug, and regular use of these medications carries a small but significant risk of gastrointestinal bleeding, which on occasion, can be life-threatening. These are important problems, which need wider recognition and detailed exploration before we can suggest widespread use of aspirin in primary or secondary prevention.

Aspirin in Older Adults: Need for Wider Utilization in Secondary Prevention and Individual Clinical Judgments in Primary Prevention.

In the treatment or secondary prevention of cardiovascular disease (CVD), there is general consensus that the absolute benefits of aspirin far outweigh the absolute risks. Despite evidence from randomized trials and their meta-analyses, older adults, defined as aged 65 years or older, are less likely to be prescribed aspirin than their middle-aged counterparts. In primary prevention, the optimal utilization of aspirin is widely debated. There is insufficient randomized evidence among apparently healthy participants at moderate to high risk of a first CVD event, so general guidelines seem premature. Among older adults, randomized data are even more sparse but trials are ongoing. Further, older adults commonly take multiple medications due to comorbidities, which may increase deleterious interactions and side effects. Older adults have higher risks of occlusive events as well as bleeding. All these considerations support the need for individual clinical judgments in prescribing aspirin in the context of therapeutic lifestyle changes and other adjunctive drug therapies. These include statins for lipids and usually multiple drugs to achieve control of high blood pressure. As regards aspirin, the clinician should weigh the absolute benefit on occlusion against the absolute risk of bleeding. These issues should be considered with each patient to facilitate an informed and person-centered individual clinical judgment. The use of aspirin in primary prevention is particularly attractive because the drug is generally over the counter and, for developing countries where CVD is becoming the leading cause of death, is extremely inexpensive. The more widespread use of aspirin in older adults with prior CVD will confer net benefits to risks and even larger net benefits to costs in the United States as well as other developed and developing countries. In primary prevention among older adults, individual clinical judgments should be made by the health-care professional and each of his or her patients.

Misperceptions of aspirin efficacy and safety may perpetuate anticoagulant underutilization in atrial fibrillation.

The general public has been conditioned over many years to accept aspirin as an effective, safe, and inexpensive remedy for heart attacks and for primary and secondary prevention of cardiovascular events. In most countries aspirin was available as an over-the-counter remedy well before its widespread use in cardiovascular disease, which probably contributed to its widespread acceptability. Moreover, many physicians took part in the physicians health study,1 a pivotal study of primary prevention in cardiovascular disease, originally promoted as showing that aspirin reduced non-fatal myocardial infarction, but without emphasis of the increase in intracranial haemorrhage and unchanged mortality in this essentially neutral study. In non-valvular atrial fibrillation (AF), aspirin has for a number of years been recommended as thrombo-prophylaxis for those not considered at high risk (see Table 1 , e.g. CHADS2 score <2).2 Unfortunately, the implied benefit of guideline approbation probably led to widespread use of aspirin as the ‘easy’, or ‘soft’ option in those at higher stroke risk with either real or perceived contra-indications to Vitamin K antagonist (VKA, e.g. warfarin). This could be the result of differences in perception among physicians and patients of the risks of stroke vs. bleeding3,4 and also the misperception that aspirin is somewhat effective in stroke prevention in this setting and has lower bleeding risk. Another possible contributory factor may be an exaggerated estimate of VKA-associated bleeding, feared by physicians who do not see the strokes prevented, but do see the bleeds. Coupled with this is the issue that VKA therapy is hard to manage, and appears to be universally disliked by physicians, patients, the media, and industry. Perhaps the connotation with …

Gastrointestinal ulcers, role of aspirin, and clinical outcomes: pathobiology, diagnosis, and treatment.

Peptic ulcer disease is a major cause of morbidity and mortality in the US with more than six million diagnoses annually. Ulcers are reported as the most common cause of hospitalization for upper gastrointestinal (GI) bleeding and are often a clinical concern due to the widespread use of aspirin and nonsteroidal anti-inflammatory drugs, both of which have been shown to induce ulcer formation. The finding that Helicobacter pylori infection (independent of aspirin use) is associated with the development of ulcers led to a more thorough understanding of the causes and pathogenesis of ulcers and an improvement in therapeutic options. However, many patients infected with H. pylori are asymptomatic and remain undiagnosed. Complicating matters is a current lack of understanding of the association between aspirin use and asymptomatic ulcer formation. Low-dose aspirin prescriptions have increased, particularly for cardioprotection. Unfortunately, the GI side effects associated with aspirin therapy continue to be a major complication in both symptomatic and asymptomatic patients. These safety concerns should be important considerations in the decision to use aspirin and warrant further education. The medical community needs to continue to improve awareness of aspirin-induced GI bleeding to better equip physicians and improve care for patients requiring aspirin therapy.

Aspirin as Adjuvant Therapy for Colorectal Cancer

EVEN BEFORE THE TIME OF HIPPOCRATES, WILLOW EXtracts, which contain salicylates, were used in medicine as analgesic, anti-inflammatory, and antipyretic agents. Acetylsalicylic acid was isolated in the mid-19th century, and since 1899 when it was patented, aspirin has enjoyed global popularity. The relatively recent discovery of its antiplatelet activity has also led to the widespread use of aspirin as an antistroke and cardioprotective agent, but the list of its medical applications continues to increase. More than 30 years ago, Sporn et al coined the term chemoprevention to describe and propose the use of oral drugs, chemicals, or supplements to reduce the risk of cancer. In the ensuing decades, chemoprevention research has generated high hopes and enormous increases in funding, although only a few agents have shown efficacy in clinical trials, and of those few, most are too toxic for use by average-risk individuals. In addition to its other effects, aspirin has been shown to be a potentially effective chemopreventive agent for a number of cancers, but most clearly for colorectal neoplasia. Numerous observational studies and randomized trials have demonstrated the efficacy of aspirin against the development of colorectal adenomas and cancer through its actions as an inhibitor of the cyclooxygenase 2 (COX-2) pathway, which is overexpressed in 80% to 85% of colorectal cancers. Nonetheless, aspirin is not recommended as a colorectal cancer chemopreventive agent because of its adverse effects— notably gastrointestinal irritation and bleeding. Specific COX-2 inhibitors, such as rofecoxib or celecoxib, which have less gastrointestinal toxicity than aspirin, also have failed to come into widespread use because of their unexpected cardiovascular toxicity. However, aspirin may now have yet another new role as a cancer treatment agent, at least in the adjuvant setting. In this issue of JAMA, Chan and colleagues report that, among patients with colorectal cancer participating in a large cohort study, aspirin users had a 29% lower cancer-specific mortality and a 21% lower overall mortality than nonusers. The reduction in mortality was even greater among patients who initiated aspirin use after cancer diagnosis than among those who used it before, and the benefit was limited to those with tumors that overexpressed COX-2. Although these findings are based on an observational study rather than an intervention trial, they meet many of the usual criteria for acceptance as valid and causal. In a previous observational study of stage III colon cancer patients treated in a randomized chemotherapy trial, Fuchs et al found similar survival benefits among consistent aspirin users. The finding that former aspirin users derived less benefit from subsequent aspirin use than former nonusers did is biologically plausible, considering the tumors that developed in former users were not prevented by aspirin use. Furthermore, the results were consistent across a variety of strata such as age, sex, and cancer site (colon vs rectum). Most compelling, the benefits of aspirin use were observed only among patients who had COX-2–expressing tumors, enhancing the biological plausibility of the findings. In the study by Chan et al, the survival benefits of aspirin were similar in patients who received standard adjuvant chemotherapy and those who did not, and in patients with stage I and stage II disease as well as those who had stage III disease at diagnosis. Thus, aspirin may have the potential to be useful as adjuvant therapy not just for locally advanced disease but for early stage patients as well. Further studies are needed to confirm and extend these findings, and should also investigate the use of aspirin as an agent in individuals with metastatic disease. One such study is the Bolus, Infusional, or Capecitabine with Camptosar-Celecoxib (BICC-C) study, which started in 2003 and randomized patients with untreated metastatic colorectal cancer to 1 of 3 chemotherapy regimens, and in addition randomized them to either a COX-2 inhibitor (celecoxib) or placebo. The COX-2 inhibitor portion of the study was discontinued in 2005 because the cardiovascular toxicity of the agent became apparent and initial results of the trial indicated no survival benefit for the celecoxib-treated group.

The cost-effectiveness of drug treatments for primary prevention of cardiovascular disease: a modelling study

Efficient prevention policies need to be informed by knowledge of the cost-effectiveness of preventive treatments. This paper calculates the cost-effectiveness of aspirin, antihypertensive treatments and statins for prevention of cardiovascular disease. The investigation is a modelling study. Ten-year cardiovascular risks and treatment eligibility were determined for each individual in a population of 5603 obtained from the Health Survey of England. Using published costs and evidence of effectiveness the cost-effectiveness of treating each eligible individual was determined over a 10-year time horizon. The marginal cost-effectiveness of additional antihypertensive drugs and increasing doses of statins were determined and a sensitivity analysis was carried out. Of the 5603 individuals 27.5% (95% confidence interval, 26.3-28.7%) were eligible for at least one treatment: the majority of these were eligible for all three. Cost per cardiovascular disease event prevented is strongly determined by pretreatment cardiovascular disease risk. In three-quarters of patients eligible for all three treatments, the lowest cost per event prevented was with aspirin and in the remainder with two-drug antihypertensive treatment. The marginal costs per event prevented were highest with the addition of a fourth antihypertensive drug and statins. These findings depend on the use of low-cost antihypertensives but are otherwise robust to a wide range of assumptions. Modelling the cost-effectiveness of treatments to prevent cardiovascular disease is feasible and provides valuable information. Cost-effectiveness analysis argues for more widespread use of aspirin and two-drug antihypertensive treatment and against the use of four-drug antihypertensive treatment or statins.

Gastrointestinal Considerations in Patients with Cardiovascular Disease Using Nonopioid Analgesics for Mild-to-Moderate Pain or Cardioprotection

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used classes of medications worldwide, available both through prescription and over the counter (OTC). Although these drugs are highly effective for pain, gastrointestinal (GI) complications may occur. Risk factors for GI complications from NSAIDs have been well studied, and the highest risk exists among the elderly and patients with a history of GI bleeding or complications. The increasingly widespread use of aspirin for both primary and secondary cardiovascular prophylaxis has also drawn attention to the potential increase in GI complications. Several strategies may minimize NSAID-mediated GI complications, including the use of drugs that do not injure the gut, such as acetaminophen or a low-dose opiate. The cyclooxygenase-2 (COX-2) inhibitors, which cause approximately 50% fewer GI complications than traditional NSAIDs, may also be used, although their cardiovascular safety has recently come into question. Antacid therapy with proton pump inhibitors (PPIs) may also be used to reduce NSAID-related dyspepsia and upper GI complications. Misoprostol is also effective in preventing NSAID-related complications, but is not as well tolerated. In any patient, the risk-benefit ratio must be assessed to determine the appropriate therapies to minimize GI complications resulting from daily aspirin therapy.

Aspirin Resistance: Definitions, Mechanisms, Prevalence, and Clinical Significance

Aspirin is the most commonly used therapeutic agent in prevention of vascular ischemic events. Aspirin exerts its antithrombotic effect primarily by interfering with the biosynthesis of thromboxane A2 (TXA2) and inhibition of TXA2 -dependent platelet aggregation. A meta-analysis of secondary prevention trials indicated that aspirin reduced major cardiovascular or cerebral events by 25%. This led to the widespread use of aspirin for prevention of cardiovascular events. However, it appears that aspirin antiplatelet effect is not uniform in all patients and previous studies estimated that 8-45% of the population were aspirin resistant. Furthermore, (i) the optimal dosage of aspirin for complete inhibition of platelet aggregation by physiological agonists (i.e arachidonic acid) is subject to great interindividual variability, (ii) the tests to detect aspirin resistance in vitro are subject to debate and (iii) the mechanisms by which some patients are resistant to aspirin in vitro remain to be determined. Despite these unresolved questions, recent clinical studies provide the reliable evidence that aspirin resistance correlates with confirmed clinical unresponsiveness, highlighting the clinical interest of determining the aspirin inhibitory effects on patients' platelets. In conclusion, discovery of aspirin resistance in individuals might be important in order to devise better anti-platelet strategies and improve our ability to prevent acute thrombotic complication.

Improving the gastrointestinal tolerability of aspirin in older people.

Interventions to reduce mortality and disability in older people are vital. Aspirin is cheap and effective and known to prevent cardiovascular and cerebrovascular disease, many cancers, and Alzheimer dementia. The widespread use of aspirin in older people is limited by its gastrointestinal side effects. Understanding age-related changes in gastrointestinal physiology that could put older people at risk of the side effects of aspirin may direct strategies to improve tolerance and hence lead to greater numbers of older people being able to take this effective intervention.

Biological Assessment of Aspirin Efficacy on Healthy Individuals

The widespread use of aspirin requires clarification of the aspirin resistance phenomenon. Most studies on this field are focused on patients which may affect the action of aspirin. We evaluated the biological efficacy of aspirin in healthy subjects. Agonist-induced platelet aggregation was fully abrogated by 100 mg of aspirin in all individuals. By contrast, with the platelet function analyzer-100 device, 33.3% of the subjects displayed no response. This failure was overcome by 500 mg or by in vitro treatment of blood with 30 mumol/L acetylsalicylic acid. Intake of 100 mg of aspirin efficiently reduced by 75% the level of 11-dehydro thromboxane B2 (11-dTxB2) in all cases. However, variability on the pre-aspirin level (range 72.4 to 625.9 ng/mmol creatinine) led to substantial differences in the residual amount of the metabolite between subjects treated with aspirin (range 12.9 to 118.0 ng/mmol creatinine). Finally, there was no influence of platelet glycoprotein IIb/IIIa (Pro33Leu), platelet glycoprotein Ia/IIa, (C807T), and FXIII (Val34Leu) polymorphisms on the efficacy of aspirin. However, the cyclooxygenase (Cox)-1 50T allele associated with higher level of 11-dTxB2, both before and after aspirin. Moreover, the Cox-2 -765C variant displayed a slightly higher reduction in 11-dTxB2 level on treatment with aspirin. Our findings suggest that full resistance of healthy subjects to aspirin is rather unlikely. However, differences in aspirin absorption, or pharmacokinetic, or other unrecognized factors may lead to lack of effect of low dose of aspirin in some subjects when using tests like platelet function analyzer-100. Whether Cox polymorphisms are thrombotic risk factor for patients under aspirin will require further research.

Controversies of Oral Antiplatelet Therapy in Acute Coronary Syndromes and Percutaneous Coronary Intervention

Platelet activation is a pivotal event in the pathophysiology of acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) and has a substantial impact on the outcomes in these settings. Aggressive implementation of antiplatelet therapy has significantly decreased adverse cardiovascular events, such as death, myocardial infarction (MI), stroke, and repeat revascularization. Although the widespread use of aspirin has contributed to this improvement, many patients continue to have a significant risk of recurrent events during the ensuing months to years. The advent of other antiplatelet agents, notably the thienopyridine clopidogrel bisulfate has heralded a new era of combined antiplatelet blockade, offering the hope of better outcomes. Recently, clinical trials have tested the use of dual oral antiplatelet blockade and have shown impressive results. Notably, the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial found that dual therapy with clopidogrel and aspirin in ACS reduced adverse cardiovascular events by 20% at 1 year (p < 0.001). The PCI-CURE substudy of CURE and the Clopidogrel for the Reduction of Events During Observation (CREDO) trial demonstrated that these benefits extend to patients undergoing both urgent and elective PCI. This article will explore the current role of and controversies in oral antiplatelet therapy after ACS and PCI.

Review article: the ageing bowel and intolerance to aspirin.

Aspirin has a role in the prevention of cardiovascular and cerebrovascular disease, Alzheimer's dementia and several cancers. Encouraging all 50 year olds to take low-dose aspirin doubles their chances of living a healthy life into their nineties. The widespread use of aspirin, however, is limited as many older subjects are currently unable to take aspirin because of gastrointestinal side-effects. This review explores why gastrointestinal events occur with aspirin use and how a net benefit from prophylactic aspirin might be achieved in older subjects. It is suggested that, by understanding the age-related changes in upper gastrointestinal physiology and the mechanisms by which aspirin leads to the risk reductions associated with its use, it may be possible to direct interventions to improve tolerability in older subjects. This would allow greater numbers of older subjects to gain the benefits associated with aspirin use.

Resistance to aspirin in vitro is associated with increased platelet sensitivity to adenosine diphosphate

Background: Platelet activation plays an important role in arterial thrombosis and the widespread use of aspirin has reduced major events by 25% in the secondary prevention of cardiovascular diseases. However, it appears that aspirin antiplatelet effect is not uniform and 8–45% of the population are, in vitro, aspirin resistant, and it is well recognized that platelets can be activated by pathways that are not blocked by aspirin, such as adenosine diphosphate (ADP). Objectives: To investigate whether aspirin-resistant patients have a modified sensitivity to ADP-induced platelet activation Material and Methods: Seventy-two patients were enrolled. Platelet function was measured by the PFA-100® analyser; platelet GP IIb–IIIa activation by ADP 10 μM was assessed by flow cytometry using PAC-1 MoAb. Results: Using a collagen/epinephrine coated cartridge on the PFA-100®, the prevalence of aspirin resistance was 29.2% ( n=21). For aspirin-resistant patients, the collagen/ADP coated cartridge showed a closure time significantly shorter ( p=0.004) compared to the sensitive and control groups. Platelets from aspirin-resistant patients bound PAC-1 significantly more ( p=0.03) than the aspirin-sensitive patients and controls when activated with 10 μM ADP. Conclusions: Platelets from aspirin-resistant patients appear to be more sensitive and activable by ADP. This hypersensitivity could provide a possible explanation for the so-called aspirin resistance, and this could justify therapeutic improvement with alternative antiplatelet agents.

Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies.

Because of the widespread use of aspirin for prevention of cardiovascular diseases, side-effects associated with thromboprophylactic doses are of interest. This study summarizes the relative risk (RR) for serious upper gastrointestinal complications (UGIC) associated with aspirin exposure in general and with specific aspirin doses and formulations in particular. After a systematic review, 17 original epidemiologic studies published between 1990 and 2001 were selected according to predefined criteria. Heterogeneity of effects was explored. Pooled estimates were calculated according to different study characteristics and patterns of aspirin use. The overall relative risk of UGIC associated with aspirin use was 2.2 (95% confidence interval (CI): 2.1, 2.4) for cohort studies and nested case-control studies and 3.1 (95% CI: 2.8, 3.3) for non-nested case-control studies. Original studies found a dose-response relationship between UGIC and aspirin, although the risk was still elevated for doses lower or up to 300 mg day(-1). The summary RR was 2.6 (95% CI: 2.3, 2.9) for plain, 5.3 (95% CI: 3.0, 9.2) for buffered, and 2.4 (95% CI: 1.9, 2.9) for enteric-coated aspirin formulations. Aspirin was associated with UGIC even when used at low doses or in buffered or enteric-coated formulations. The latter findings may be partially explained by channeling of susceptible patients to these formulations.

Combined effects of aspirin and the novel antiplatelet agent clopidogrel on platelet function in vivo and in vitro

Abstract Background The platelet adenosine 5′-diphosphate (ADP) receptor antagonist clopidogrel has proved an effective antiplatelet agent in the prevention of arterial thrombosis. In the vast majority of studies clopidogrel has been used as an alternative to aspirin, but the widespread use of aspirin, and the different modes of actions of the two drugs, makes it important to determine the safety and efficacy of using both drugs in combination. This study reports the effect of this drug combination on bleeding times and platelet function in humans. Methods The study was conducted in normal, healthy subjects to evaluate the effects of different doses of clopidogrel on bleeding time, platelet aggregation and activation, above a baseline of standard aspirin therapy. Seven normal men (mean age 30 years) were given aspirin (150 mg) for 3 days. Subjects received clopidogrel (75 mg) at 24 and 48 h, followed by a third dose of clopidogrel (300 mg) on day 3. Results The combination of aspirin plus clopidogrel leads to a significant reduction in platelet function relative to aspirin alone (P &amp;lt; 0·05), and is associated with a significant increase in the bleeding time (P &amp;lt; 0·05). The response to collagen was similarly affected. Platelet fibrinogen binding in response to both ADP and thrombospondin-related adhesive protein was reduced only partially by aspirin, but significantly reduced by both doses of clopidogrel (P &amp;lt; 0·05 for all). P-selectin expression in response to both agonists was also reduced, but not significantly. Basal levels of fibrinogen binding, P-selectin, glycoprotein (GP) IIb–IIIa and GPIb expression were not affected by treatment. Conclusion Blocking both the cyclo-oxygenase and ADP pathways of platelet activation has a profound effect on platelet response to agonists, which may offer significant potential benefit in preventing thrombotic events relative to aspirin alone. Achieving the correct balance between haemostasis and thrombosis with these useful agents will require further study.

Possible interaction between aspirin and ACE inhibitors: update on unresolved controversy.

The widespread use of aspirin and angiotensin converting enzyme (ACE) inhibitors in patients with coronary artery disease contributes significantly to the reduction in morbidity and mortality from this common health problem. These agents are widely and concomitantly used, and they share mechanisms that may interact in negative or positive pathways. Data derived from in vitro preparations, animal studies, human studies, and case-control studies are inconsistent. No study has established firm evidence regarding the safety or adverse effect of aspirin on patients who are on ACE inhibitors. The efficacy and safety of aspirin in combination with ACE inhibitors has been questioned and debated. If a negative interaction does exist, it will affect daily practice in treating patients with coronary artery disease and heart failure. This article reviews the available data regarding the safety of combined aspirin and ACE-inhibitor treatment among patients with ischemic heart disease, to assess the possible interaction between the two drugs and to discuss the significance and implications of the data. (c)2000 by CHF, Inc.

Antiplatelet therapy in coronary artery disease: review and update of efficacy studies.

The mechanisms of action of currently available and newer antiplatelet agents and evidence of the efficacy of antiplatelet agents for primary and secondary prevention of coronary artery disease are reviewed. Available data do not support the widespread use of aspirin for primary prevention of cardiovascular disease. Patients over the age of 50 years with at least one additional risk factor for coronary artery disease may benefit, although possibly at an increased risk of hemorrhagic stroke. Aspirin is recommended for secondary prevention of vascular disease in patients with stable or unstable angina, clinical or laboratory evidence of coronary artery disease, history of myocardial infarction, or history of stroke or transient ischemic attack. There are no data supporting a role for dipyridamole for primary or secondary prevention of ischemic heart disease. Abciximab has been shown to reduce the risk of cardiovascular complications at 30 days after percutaneous transluminal coronary angioplasty in patients with refractory unstable angina. Studies with other glycoprotein IIb/IIIa-receptor antagonists, including eptifibatide, tirofiban, and lamifiban, have yielded promising results. Ticlopidine may be used for secondary prevention of cardiovascular disease in patients with unstable angina who are allergic to or intolerant of aspirin. Clopidogrel has been shown to be safe and effective for secondary prevention of vascular events. Aspirin has a role in secondary prevention of coronary artery disease; among patients who are allergic to or intolerant of aspirin, ticlopidine has a role in patients with unstable angina and clopidogrel has a potential role in patients with ischemic heart or vascular disease.

Therapy for Bleeding Peptic Ulcers

During the past 50 years, mortality from acute bleeding in the upper gastrointestinal tract has remained at 6 to 10 percent, despite improved medical and surgical treatments, the development of diagnostic and therapeutic endoscopy, and the availability of intensive care units.1 One contributing factor is that patients tend to be older and to have more coexisting illnesses than ever before.2 The widespread use of aspirin and other nonsteroidal antiinflammatory agents, even at low doses taken to prevent cardiovascular disease, has also substantially increased the risk of bleeding.3 Fortunately, in 70 to 80 percent of patients with upper gastrointestinal bleeding, the . . .

Potentiation of heat stress-induced hsp70 expression in vivo by aspirin.

Studies in cultured cells have demonstrated that non-steroidal anti-inflammatory agents can potentiate heat-induced hsp70 expression through activation of HSF1 to a DNA binding state. We investigated the influence of aspirin on hsp70 expression in intact rats subjected to heat stress. Rats were injected intraperitoneally either with aspirin (100 mg/kg) or vehicle alone, 60 min prior to their placement at 37 degrees C or room temperature for 30 min. hsp70 mRNA expression was analyzed in lung, liver and kidney isolated from animals assigned to one of four different treatment paradigms; untreated controls, heat, aspirin, and aspirin-plus-heat. Comparison of hsp70 expression in the treatment groups revealed that in all tissues examined, aspirin-plus-heat treatment resulted in 3-4 fold higher levels of hsp70 mRNA relative to those seen with heat treatment alone. Little or no hsp70 mRNA expression was detected in the unheated groups, regardless of aspirin treatment. In keeping with the mRNA expression, Hsp70 protein levels were also elevated in aspirin-plus-heat treated animals. Aspirin treatment did not alter hsp70 protein expression in the absence of heat. In contrast to in vitro observations, aspirin treatment in vivo did not alter HSF1 DNA binding properties. Core body temperature measurements revealed that aspirin pretreatment enhanced the rise in body temperature seen in response to heat treatment. This increased hyperthermic response to heat stress probably accounts for the potentiation of hsp70 expression observed in aspirin-plus-heat treated rats. Given the widespread use of aspirin in humans within a dose range comparable to that used here, our findings are likely to have important physiological consequences.