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PubMed2005

Aspirin resistance: moving forward with multiple definitions, different assays, and a clinical imperative.

Many patients are treated with aspirin to prevent a serious vascular event, most notably myocardial infarction and stroke. A growing number of studies have been appearing in the literature that indicate a significant fraction of aspirin-treated patients may be resistant to the antiplatelet effects of the drug. Resistance to aspirin may be related to the concomitant ingestion of aspirin and nonsteroidal anti-inflammatory drugs, which impairs the aspirin effect, or to more complex situations, such as metabolic defects that diminish the therapeutic effect of aspirin. The incidence of aspirin resistance is unknown, but it may approach 20% to 30%. The diagnosis of aspirin resistance has been evaluated using multiple assays, and because there are multiple assays, this has resulted in multiple definitions for aspirin resistance. This review considers aspirin resistance at a time when there is confusion about the definition, and the clinical assay to best assess it, because there is a clinical imperative to know now which patients taking aspirin are not receiving a therapeutic effect.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Community pharmacy Target Intervention Program to improve aspirin use in persons with diabetes.

OBJECTIVE: To identify the rate of aspirin or antiplatelet/anticoagulant use in persons with diabetes presenting to community pharmacies and determine whether a student pharmacist-driven Target Intervention Program (TIP) could increase the number of eligible persons with diabetes receiving aspirin therapy in accordance with American Diabetes Association (ADA) recommendations. DESIGN: Unblinded, single intervention. SETTING: Eight Community Pharmacy Advanced Practice Experience (CPAPE) sites in New York State. PARTICIPANTS: Persons having prescriptions filled for diabetes medications or supplies who were not receiving antiplatelet/anticoagulant medications. INTERVENTIONS: Assessment sheets were completed by student pharmacists for eligible patients to determine appropriateness for aspirin therapy. Recommendations for aspirin therapy were faxed to physicians when indicated, and physicians responded via fax for aspirin therapy implementation. The student pharmacists contacted patients, informed patients of physician decisions, and provided appropriate counseling. MAIN OUTCOME MEASURES: Number of persons with diabetes currently receiving aspirin or antiplatelet/anticoagulant medications and the number initiated on aspirin as a result of the TIP. RESULTS: A total of 436 persons with diabetes were identified. Of those contacted, 322 agreed to participate and 31 declined; 228 were taking aspirin or other antiplatelet/anticoagulant agents at baseline. Students completed assessment sheets, which were forwarded to physicians, for 79 subjects potentially eligible to receive aspirin therapy; 65 physician responses were received (82% response rate). Aspirin therapy was initiated in 53 patients (67%). CONCLUSION: The TIP enabled CPAPE students to increase aspirin use among eligible persons with diabetes in accordance with ADA guidelines.

Aspirin↗
PubMed2005

Underutilization of aspirin persists in US ambulatory care for the secondary and primary prevention of cardiovascular disease.

BACKGROUND: Despite the proven benefits of aspirin therapy in the primary and secondary prevention of cardiovascular disease (CVD), utilization rates of aspirin remain suboptimal in relation to recommendations. We studied national trends of aspirin use among intermediate- to high-risk patients in the US ambulatory care settings and compared the priority given to aspirin versus statins for CVD risk reduction. We also examined patient and health care provider contributors to the underuse of aspirin. METHODS AND FINDINGS: We used the 1993-2003 US National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey to estimate aspirin use by cardiovascular risk. Physician-noted cardiovascular diseases defined high risk. Intermediate risk was defined as having diabetes mellitus or multiple major risk factors. The proportion of patient visits in which aspirin was reported increased from 21.7% (95% confidence interval: 18.8%-24.6%) in 1993-1994 to 32.8% (25.2%-40.4%) in 2003 for the high-risk category, 3.5% (2.0%-5.0%) to 11.7% (7.8%-15.7%) for visits by patients diagnosed with diabetes, and 3.6% (2.6%-4.6%) to 16.3% (11.4%-21.2%) for those with multiple CVD risk factors. Beginning in 1997-1998, statins were prioritized over aspirin as prophylactic therapy for reducing CVD risk, and the gaps remained wide through 2003. In addition to elevated CVD risk, greater aspirin use was independently associated with advanced age, male gender, cardiologist care, and care in hospital outpatient departments. CONCLUSION: Improvements in use of aspirin in US ambulatory care for reducing risks of CVD were at best modest during the period under study, particularly for secondary prevention, where the strongest evidence and most explicit guidelines exist. Aspirin is more underused than statins despite its more favorable cost-effectiveness. Aggressive and targeted interventions are needed to enhance provider and patient adherence to consensus guidelines for CVD risk reduction.

Adult↗
PubMed2003

Antagonism of the acute hemodynamic effects of captopril in decompensated congestive heart failure by aspirin administration.

The concomitant use of angiotensin-converting enzyme inhibitors and aspirin may cause pharmacological antagonism. Hence we examined the effect of aspirin on the neurohormonal function and hemodynamic response to captopril in heart failure patients. Between April 1999 and August 2000, 40 patients were randomized into four equal groups: 1) captopril, 2) aspirin, 3) captopril-aspirin: captopril was given alone on the first day, followed by aspirin on the remaining days, and 4) aspirin-captopril: aspirin was given alone on the first day, followed by captopril on the remaining days. Hemodynamic, norepinephrine and prostaglandin measurements were performed pre- and post-medication for 4 days. Captopril (50 mg) was given orally every 8 h and 300 mg aspirin was given on the first day, and 100 mg/day thereafter. In the captopril group and only on the first day of captopril-aspirin, captopril produced increases in cardiac index (2.1 +/- 0.6 to 2.5 +/- 0.5 l min-1 m-2, P<0.0001), and reduced peripheral vascular resistance (1980 +/- 580 to 1545 +/- 506 dyn s-1 cm-5/m , P<0.0001) and pulmonary wedge pressure (20 +/- 4 to 15 +/- 4 mmHg, P<0.0001). In contrast, aspirin alone or associated with captopril showed no significant hemodynamic changes. Norepinephrine decreased (P<0.02) only in the captopril group. Prostaglandin levels did not differ significantly among groups. Thus, aspirin compromises the short-term hemodynamic and neurohormonal effects of captopril in patients with acute decompensated heart failure.

Aged↗
PubMed2005

Aspirin resistance: an evaluation of current evidence and measurement methods.

Aspirin resistance is a poorly characterized phenomenon, whereby certain patients do not benefit from the antithrombotic effect of aspirin. The frequency of aspirin resistance is unknown, but estimates range from 5-60%. The mechanism of aspirin resistance also is unknown; proposed mechanisms are poor patient compliance, poor aspirin absorption, increased isoprostane activity, platelet hypersensitivity to agonists, increased cyclooxygenase-2 activity, a cyclooxygenase-1 polymorphism, and the platelet alloantigen 2 polymorphism of platelet glycoprotein IIIa. Aspirin resistance appears to be dose related in some patients and therefore may be overcome with high doses. Evidence indicates that aspirin resistance is a dynamic state, with significant intrapatient variability in aspirin sensitivity with time. To date, a sensitive and specific assay of aspirin effect that reliably predicts treatment failure has not emerged. However, several commercially available products are being marketed for this purpose without convincing clinical data. Despite a wealth of literature on the topic, aspirin resistance remains an enigma. Further investigation is needed regarding strategies to identify and treat patients resistant to aspirin.

Antigens, Human Platelet↗
PubMed2003

Improving aspirin prophylaxis in a primary care diabetic population.

STUDY OBJECTIVE: To evaluate and improve adherence to American Diabetes Association guidelines for prophylactic aspirin therapy in ambulatory patients with diabetes using a pharmacy-directed intervention. DESIGN: Unblinded, single intervention. SETTING: Rural, primary care clinic. SUBJECTS: Eighty-five patients with a diagnosis of diabetes mellitus. INTERVENTION: Patients with diabetes were identified from database searches and routine clinic visits. Medical records were screened for aspirin use, allergies, adverse events, and contraindications. During routine clinic visits or structured telephone interviews, patients with indications for aspirin therapy were advised to begin enteric-coated aspirin 81 mg/day A follow-up survey assessed adherence. MEASUREMENTS AND MAIN RESULTS: At baseline, 28 (33%) of 85 patients were receiving aspirin therapy An additional 8 patients had contraindications to aspirin, and 2 patients had no indications for aspirin therapy Aspirin was recommended to 27 patients during clinic interventions and to 15 patients during telephone interventions. Two patients declined the recommendation. At the completion of this intervention, 70 (82%) of 85 patients were receiving daily aspirin or had accepted the recommendation to begin therapy. CONCLUSIONS: A pharmacy-directed intervention increased prophylactic aspirin therapy in patients with diabetes from 33% of patients at baseline to 82% at the end of the study The intervention, which has a simple, patient-focused design, serves as a template for improving aspirin prophylaxis among patients with diabetes in other ambulatory settings.

Aspirin↗
PubMed2003

Aspirin dosage and thromboxane synthesis in patients with vascular disease.

STUDY OBJECTIVE: To determine whether urinary 11-dehydrothromboxane B2 (d-TXB2) is a marker of aspirin resistance and define the relationship between aspirin dosage and concentrations of this thromboxane metabolite. DESIGN: Randomized, crossover study. SETTING: Two outpatient clinical centers. PATIENTS: Forty-eight patients (mean age 70 yrs) with vascular disease (52% clinical coronary artery disease, 29% cerebrovascular disease, 46% atrial fibrillation). INTERVENTION: Levels of serum thromboxane B2 and d-TXB2 were measured after patients were treated initially with aspirin 325 mg/day for 4 weeks, then again after random assignment to receive aspirin 81, 325, or 1300 mg/day for 4 weeks, and then again after resumption of 325 mg/day for 4 weeks. MEASUREMENTS AND MAIN RESULTS: During treatment with aspirin 325 mg/day, the mean +/- SD serum thromboxane B2 level was 0.9 +/- 1.2 ng/ml and median (interquartile range) was 0.4 (0.2-0.9) ng/ml. Mean urinary d-TXB2 was 16 +/- 7.9 ng/mmol creatinine, with a median of 15 (9.9-23) ng/mmol creatinine with aspirin 325 mg/day. After 4 weeks of aspirin 81 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p=0.04) were both significantly higher compared with aspirin 325 mg/day; for urinary d-TXB2, the median increase was 3.0 ng/mmol creatinine. After 4 weeks of treatment with aspirin 1300 mg/day, levels of serum thromboxane B2 (p<0.01) and urinary d-TXB2 (p<0.01) were both significantly lower compared with aspirin 325 mg/day; the median decrease in urinary d-TXB2 was 4.4 ng/mmol creatinine. CONCLUSION: Different aspirin dosages significantly affect serum and urinary markers of thromboxane synthesis.

Aged↗
PubMed2003

Risks versus benefits of NSAIDs including aspirin in myocarditis: a review of the evidence from animal studies.

NSAIDs, including aspirin (acetylsalicylic acid), are frequently used and effective in a broad variety of inflammatory diseases, i.e. rheumatic carditis and pericarditis. Myocarditis may constitute another suitable indication for NSAIDs in order to relieve the symptoms of the presumed viral infection or because pericardial effusion is often associated with this condition. However, concerns have been raised about their indiscriminate use in myocarditis. To clarify this issue, we conducted a systematic review of the literature concerning myocarditis, aspirin and NSAIDs. We examined five animal studies of NSAIDs (indomethacin and ibuprofen) and aspirin in coxsackievirus B3- and B4-induced myocarditis. These studies indicated a deleterious effect of NSAIDs and aspirin in this setting, demonstrating a 2- to 3-fold increase in inflammation, myocytes necrosis and even mortality when compared with placebo. This possible deleterious effect was more predominant when NSAIDs or aspirin were administered during the acute and subacute phases of myocarditis; however, it was still noted when NSAIDs were administered during the late phase of the disease (the effect of aspirin was not evaluated in late phase studies). According to these animal studies, such effect might be attributed to decreased viral clearance (possibly via interferon inhibition) and/or exaggerated cytotoxic response (via interleukin-2 or inhibition of suppressor cells factors) and/or coronary artery spasm. We found one animal study looking at autoimmune myocarditis and it did not demonstrate any beneficial or detrimental effect of aspirin. Moreover, recent data suggest that aspirin and NSAIDs may counteract part of the efficacy of ACE inhibitors and be deleterious in chronic heart failure. Taken together, these studies point to a possible deleterious effect of aspirin and NSAIDs in human myocarditis. In view of these animal studies and in the absence of controlled studies of aspirin or NSAIDs in human myocarditis, we do not recommend indiscriminate treatment with NSAIDs or high-dose aspirin in patients with myocarditis where there is no or minimal associated pericarditis.

Animals↗
PubMed2006

A multi-country economic evaluation of low-dose aspirin in the primary prevention of cardiovascular disease.

BACKGROUND: Low-dose aspirin (acetylsalicylic acid) is standard care in patients with a history of cardiovascular disease (CVD). The use of low-dose aspirin in primary prevention is not yet fully established, although meta-analyses and US and European guidelines support its use in people at increased risk of CVD. The primary objective of this study was to assess the economic consequences of the use of low-dose aspirin in the primary prevention of CVD in four European countries (UK, Germany, Spain and Italy). METHODS: Based on results (benefits and harms) reported in meta-analyses, a state-transition model was developed to predict the cost effectiveness of low-dose aspirin in the primary prevention of CVD. The model consists of five health states: no history of CVD, history of stroke, history of myocardial infarction (MI), history of stroke and MI, and death. A 10-year time horizon and 1-year cycles were used. Secondary prevention data were derived from the aspirin arm of the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) study. Direct costs from the public healthcare payer's perspective were used (euro, 2003 values). Effects were expressed in life-years (LY) and QALYs gained. Quality weights were obtained from published data.Country-specific discounting was applied on effects and costs (3.5% for the UK, 5% for Germany and 3% for Spain and Italy). Univariate sensitivity analysis and Monte Carlo simulation were performed to assess uncertainty in the results. RESULTS: For patients with an annual risk of coronary heart disease (CHD) of 1.5%, the model resulted in 10-year savings with low-dose aspirin of on average euro 201 (95% CI 81, 331), euro 281 (95% CI 141, 422), euro 797 (95% CI 301, 1331) and euro 427 (95% CI 122, 731) per patient in the UK, Germany, Spain and Italy, respectively. Average total cost was almost 3- to 4-fold higher in Spain and Italy than in the UK and Germany. Savings (non-significant) start in the first year of treatment in all countries. Sensitivity analyses on cost of complications, utility, discounting, stroke rate and gastrointestinal bleeding rate showed the robustness of the results. From an annual risk of CHD of 0.236% for the UK, 0.324% for Germany, 0.244% for Spain and 0.560% for Italy, low-dose aspirin was cost saving compared with placebo. Monte Carlo analysis showed aspirin dominance in about 97% of cases for the three studied annual risks of CHD (0.6%, 1.0% and 1.5%) in the UK, Germany and Spain. In Italy, aspirin dominance in > 95% of cases was seen at annual risks of 1% and 1.5%. CONCLUSIONS: Administering low-dose aspirin to patients with an annual risk of CHD of > or = 1% appears to be significantly cost saving from the healthcare payer's perspective in all countries analysed. Sensitivity analyses (CHD risk and bleedings) suggested the results were robust.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Aspirin reduces experimental cerebral blood flow in vivo.

Aspirin therapy for stroke prophylaxis in low risk patients has paradoxically demonstrated an increased risk of ischemic stroke in several studies. Moreover, the MAST-Italy trial reported a near doubling of mortality with the addition of aspirin to thrombolytics while experimentally, we have noted that aspirin antagonizes t-PA-mediated clot lysis. The mechanisms responsible for these observations is unclear. Of interest, few studies have examined the effect of aspirin on cerebral blood flow (CBF). The objective of this study was to examine the acute effect of high dose aspirin on CBF in a rabbit model. Mean arterial pressure, arterial blood gases, and core and brain temperature were controlled throughout the protocol. CBF, measured by the technique of hydrogen clearance using Platinum-Iridium flow probes, was measured before and 20 min following aspirin administration (20 mg kg-1 i.v.) in a cohort of 50 rabbits and compared to rabbits receiving vehicle (n = 19). Following aspirin therapy, CBF (cc/100 g-1 min-1) was reduced from 80.8 +/- 27.4 to 65.1 +/- 31.7 (mean +/- SD), a reduction to 80.4 +/- 21.3% of baseline (p < 0.00001, t-test), whereas CBF in the control group remained unchanged (81.0 +/- 25.4 vs. 77.5 +/- 24.0, mean +/- SD). Thus aspirin acutely reduced CBF by approximately 20% in a rabbit model, perhaps related to inhibitory effects on prostacyclin and/or nitric oxide. This result may help explain the possible increase in ischemic stroke seen in low risk patients on aspirin therapy. A reduction in CBF by aspirin may also assist in understanding the antagonism of t-PA-mediated clot lysis by aspirin seen in our rabbit model of thromboembolic stroke, particularly since all agents which share the ability to reverse this antagonism (nitric oxide donors, beta blockers, hydralazine, prostacyclin) also increase CBF by approximately 20%. Future strategies for 'antiplatelet' therapy may benefit from using agents which do not adversely affect CBF.

Animals↗
PubMed2000

Comparison of the pharmacokinetic profiles of soluble aspirin and solid paracetamol tablets in fed and fasted volunteers.

The aim of this study was to investigate the absorption of popular preparations of two common analgesics--soluble aspirin and solid paracetamol tablets. An open, randomised, crossover study design was used to compare the pharmacokinetic parameters of soluble aspirin and solid paracetamol tablets in 16 healthy, male volunteers from the University of the Witwatersrand, South Africa, in both fed and fasted states. Plasma concentrations of paracetamol, aspirin and salicylic acid were measured. It was found that the rate of absorption was significantly faster for soluble aspirin than for solid paracetamol, regardless of fed or fasting state, considering time to maximum concentration (p < 0.01), time to first quantifiable concentrations (p < 0.05) and absorption rate (p < 0.01). Absorption rate was significantly affected by food for both soluble aspirin (p = 0.028) and for solid paracetamol (p = 0.0003). Time to maximum concentration was not significantly affected by food for soluble aspirin (p = 0.17) but significantly lengthened for solid paracetamol (p = 0.0003). The extent of absorption was affected by food in terms of maximum concentration for both drugs (p = 0.0001), with a reduction of 49% in the fed state for solid paracetamol compared to 18% for soluble aspirin, the difference between the drugs being statistically significant (p = 0.0024). The overall bioavailability of soluble aspirin was unaffected by food and the bioavailability of salicylic acid was increased in the fed state, whereas that of solid paracetamol was lowered in the fed state. Greater inter-individual variation was seen in paracetamol concentrations compared with aspirin or salicylic acid levels. In conclusion, these results show that the absorption of soluble aspirin is largely unaffected by food, whereas, in the same volunteers, the absorption of solid paracetamol tablets is greatly affected. In some volunteers, maximum plasma concentrations of paracetamol following food did not reach levels previously reported to be required for effective analgesia, and this may have implications for pain relief in some individuals. The practice in some individuals of taking aspirin tablets after food to minimise potential gastric disturbance should not affect the level of analgesia.

Acetaminophen↗
PubMed2003

A novel mechanism for aspirin-mediated growth inhibition of human colon cancer cells.

PURPOSE: The molecular mechanisms by which aspirin and other nonsteroidal anti-inflammatory drugs exert chemopreventative effects in colon cancer are unclear and complex. Current investigations focus on the chemopreventive properties of nonsteroidal anti-inflammatory drugs, independent of their ability to inhibit cyclooxygenase (COX) activity, and presumably, identification of non-COX pathways will suggest new targets for clinical use. It was demonstrated recently that aspirin results in reduced microsatellite instability in colorectal cancer cells. We hypothesized that aspirin treatment might alter expression of DNA mismatch repair (MMR) proteins, representing another potential non-COX mechanism for its action. EXPERIMENTAL DESIGN: In this study, we have examined the effects of aspirin on the cellular growth rates, MMR protein levels, cell cycle analysis and apoptosis in MMR-deficient (HCT116) and MMR-proficient (HCT116+chr3 and SW480) human colon cancer cell lines. RESULTS: We found that treatment with aspirin inhibited the growth of these three cancer cell lines. In HCT116+chr3 cells, treatment with 1 mM of aspirin increased expression of the hMLH1 and hPMS2 proteins by 2.5-fold and 2-fold, respectively, and increased expression of the hMSH2 and hMSH6 proteins by 2-3-fold. For SW480 cells, treatment with 1 and 5 mM of aspirin increased expression of the hMLH1 and hPMS2 proteins by 2-4-fold and 3-5-fold, respectively, and increased expression of the hMSH2 and hMSH6 proteins by 3-7-fold. For all three of the cell lines, treatment with 1 and 2.5 mM of aspirin induced apoptosis at 48 and 72 h. Aspirin induced G(0)/G(1) cell cycle arrest in HCT116 cells. CONCLUSIONS: We conclude that aspirin acts through COX-independent mechanisms by resulting in an increase in MMR protein expression and subsequent apoptosis, which might serve as an additional means of growth inhibition in aspirin-treated human colon cancer cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

[Asthma with hypersensitivity to aspirin].

Aspirin-induced asthma (AIA) is a distinct clinical entity characterised by hypersensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) typically occurring in the form of asthma and severe rhinosinusitis. Its prevalence is about 10%, but AIA probably is underdiagnosed. The diagnosis can only be established with certainty by challenge tests, using increasing doses of aspirin. The crucial cell in AIA is the eosinophil, while the role of mast cell is more elusive. At the biochemical level, AIA is distinguished by profound underlying arachidonic acid disturbances. An overproduction of leukotrienes was observed in patients with aspirin hypersensitivity at baseline and following aspirin challenge. In some patients altered prostaglandin release following aspirin was encountered. The inhibition of COX-1, but not COX-2, was shown to precipitate post-challenge symptoms precipitated by aspirin. The new insights into eicosanoid molecular biology and genetics have recently emerged. The patients with aspirin-sensitive asthma require often prolonged oral, inhaled and nasal corticotherapy. Antileukotrienes also can be used. Aspirin and NSAIDs should be avoided. Nevertheless, highly specific COX-2 inhibitors are well tolerated. Aspirin desensitisation, followed by daily aspirin treatment, is a valuable therapeutic option.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Aspirin as an antithrombotic drug: from the aggregometer to clinical trials.

Aspirin inhibits thromboxane A2 and prostaglandin formation in platelets and prostaglandin I2 (prostacyclin) in vascular cells. It prevents platelet aggregation by irreversible acetylation of cyclooxygenase, a key enzyme in the arachidonic acid metabolism. Oral aspirin can be extensively hydrolyzed to inactive salicylate in the stomach and the liver (first-pass) before it enters the systemic circulation. Presystemic acetylation of platelets thus occurs during aspirin absorption, with a concomitant sparing of peripheral vascular cyclo-oxygenase, mainly exposed to salicylate. On the basis of its antiplatelet effect, aspirin has been assessed during the past two decades in patients with a history of myocardial infarction, stroke, transient ischemic attack or unstable angina. A meta-analysis of randomized controlled trials of long term aspirin treatment for secondary prevention of vascular disease indicated that aspirin (300-1500 mg daily) significantly reduced fatal and non-fatal vascular events. More recently aspirin (160 mg daily) produced a significant reduction in hospital vascular mortality and in non-fatal events in patients with suspected acute myocardial infarction. Combination of aspirin with streptokinase was significantly better than either drug alone. On the other hand two primary prevention trials of aspirin in healthy doctors did not show any modification of vascular mortality despite an overall reduction of non-fatal myocardial infarction. Resolution of some problems related to the mechanism of action of aspirin and to selection of trial populations will possibly increase the benefit/risk ratio of aspirin treatment for prevention of vascular disease.

Aspirin↗
PubMed1984

Plasma levels of salicylate and aspirin in healthy volunteers: relevance to drug interaction on platelet function.

Salicylate can prevent the inhibitory effect of aspirin on platelet cyclooxygenase activity. We investigated whether salicylate and aspirin interact in platelets in humans at doses and plasma levels of clinical relevance. In our first experiment in healthy volunteers, the lowest dose of intravenously administered aspirin that suppressed arachidonate-induced platelet aggregation and serum immunoreactive thromboxane B2 generation was 40 mg. In our second experiment, volunteers given oral doses of sodium salicylate (250 or 1000 mg) had peak plasma salicylate levels averaging 20 and 76 micrograms/ml, respectively. Neither platelet aggregation or thromboxane B2 formation was modified by either salicylate treatment. Forty minutes later, all six volunteers received 40 mg of aspirin intravenously. Aspirin levels were not affected by previous salicylate ingestion, but inhibition by aspirin of both platelet aggregation and thromboxane B2 generation was significantly prevented by the higher salicylate dose. In our last experiment, peak plasma levels of aspirin and salicylate were measured in healthy volunteers after ingestion of either 320 mg of compressed or 800 mg of enteric-coated aspirin. Salicylate levels averaged 19 and 51 micrograms/ml, respectively, after the lower and higher doses of aspirin, whereas aspirin averaged 3 micrograms/ml after either dose. Serum thromboxane B2 generation was almost completely inhibited 1 hour after either aspirin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated aspirin administration.

OBJECTIVES: The purpose of this study was to assess gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated aspirin. METHODS: A total of 47 healthy volunteers participated in randomized, controlled acute and chronic trials. Seventeen participated in a repeated measures acute trial, and 30 participated in an independent sample chronic trial. Gastrointestinal blood loss was determined by obtaining 72-hour stool collections and quantitating Chromium-51 labeled erythrocytes. RESULTS: Acute phase trials: gastrointestinal blood loss during base line was 0.47 (+/- 0.11) mL/day, 0.96 (+/- 0.12) mL/day with enteric-coated aspirin (p < 0.0006), and 1.82 (+/- 0.35) mL/day with plain aspirin (p < 0.0001 vs. base line, p = 0.0476 vs. enteric-coated aspirin). Chronic phase trials: gastrointestinal blood loss was 1.12 (+/- 0.31) mL/day with enteric-coated aspirin (p = 0.0024 vs. control) and 2.60 (+/- 0.68) with plain aspirin (p < 0.0001 vs. control, p = 0.0364 vs. enteric-coated aspirin). CONCLUSIONS: During acute and chronic ingestion, plain aspirin at a dose of 325 mg/day significantly increased gastrointestinal blood loss when compared to control or enteric-coated aspirin values, although enteric-coated aspirin values were also significantly increased compared to control. Gastric adaptation does not decrease blood loss with low dose aspirin consumption.

Adaptation, Physiological↗
PubMed1993

Aspirin use and risk of fatal cancer.

Aspirin and other nonsteroidal antiinflammatory drugs inhibit prostaglandin synthesis and tumor growth in many experimental systems, but it is unclear which of these tumor models are relevant to humans. We have reported reduced risk of fatal colon cancer among persons who used aspirin in a large prospective study. This analysis examines other fatal cancers in relation to aspirin among 635,031 adults in that study who provided information in 1982 on the frequency and duration of their aspirin use and did not report cancer. Death rates were measured through 1988. Death rates decreased with more frequent aspirin use for cancers of the esophagus, stomach, colon, and rectum but not generally for other cancers. For each digestive tract cancer, death rates were approximately 40% lower among persons who used aspirin 16 times/month or more for at least 1 year compared to those who used no aspirin. The trend of decreasing risk with more frequent aspirin use was strongest among persons who had used aspirin for 10 years or more; it remained statistically significant, except for esophageal cancer, in multivariate analyses that adjusted for other known risk factors. Biases such as early detection or aspirin avoidance among cases do not appear to explain the results. Our data suggest that regular, prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus, stomach, colon, and rectum. Future epidemiological and basic research should examine all digestive tract cancers in considering the chemopreventive or therapeutic potential of nonsteroidal antiinflammatory drugs.

Acetaminophen↗
PubMed1996

Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. A meta-analysis.

OBJECTIVE: To estimate the risk of myocardial infarction (MI) and death in patients with unstable angina who are treated with aspirin plus heparin compared with patients treated with aspirin alone. DATA SOURCES: Studies were retrieved using MEDLINE, bibliographies, and consultation with experts. STUDY SELECTION: Only published trials that enrolled patients with unstable angina, randomized participants to aspirin plus heparin vs aspirin alone, and reported incidence of myocardial infarction or death were included in the meta-analysis. DATA EXTRACTION: Patient outcomes including MI or death, recurrent ischemic pain, and major bleeding during randomized treatment; revascularization procedures after randomization; and MI or death during the 2 to 12 weeks following randomization were extracted by 2 authors, 1 of whom was blinded to the journal, institution, and author of each study. DATA SYNTHESIS: Six randomized trials were included. The overall summary relative risk (RR) of MI or death during randomized treatment was 0.67 (95% confidence interval [CI], 0.44-1.02) in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The summary RRs for secondary endpoints in patients treated with aspirin plus heparin compared with those treated with aspirin alone were 0.68 (95% CI, 0.40-1.17) for recurrent ischemic pain; 0.82 (95% CI, 0.56-1.20) for MI or death 2 to 12 weeks following randomization; 1.03 (95% CI, 0.74-1.43) for revascularization; and 1.99 (95% CI, 0.52-7.65) for major bleeding. We found no statistically significant heterogeneity among individual study findings. CONCLUSIONS: Our findings are consistent with a 33% reduction in risk of MI or death in patients with unstable angina treated with aspirin plus heparin compared with those treated with aspirin alone. The bulk of evidence suggests that most patients with unstable angina should be treated with both heparin and aspirin.

Angina, Unstable↗