Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ASPIRIN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2005

Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer.

CONTEXT: Randomized trials of short-term aspirin use for prevention of recurrent colorectal adenoma have provided compelling evidence of a causal relationship between aspirin and colorectal neoplasia. However, data on long-term risk of colorectal cancer according to dose, timing, or duration of therapy with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) remain limited. OBJECTIVE: To examine the influence of aspirin and NSAIDs in prevention of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 82 911 women enrolled in the Nurses' Health Study providing data on medication use biennially since 1980 and followed up through June 1, 2000. MAIN OUTCOME MEASURE: Incident colorectal cancer. RESULTS: Over a 20-year period, we documented 962 cases of colorectal cancer. Among women who regularly used aspirin (> or =2 standard [325-mg] tablets per week), the multivariate relative risk (RR) for colorectal cancer was 0.77 (95% confidence interval [CI], 0.67-0.88) compared with nonregular users. However, significant risk reduction was not observed until more than 10 years of use (P< or =.001 for trend). The benefit appeared related to dose: compared with women who reported no use, the multivariate RRs for cancer were 1.10 (95% CI, 0.92-1.31) for women who used 0.5 to 1.5 standard aspirin tablets per week, 0.89 (95% CI, 0.73-1.10) for 2 to 5 aspirin per week, 0.78 (95% CI, 0.62-0.97) for 6 to 14 aspirin per week, and 0.68 (95% CI, 0.49-0.95) for more than 14 aspirin per week (P<.001 for trend). Notably, women who used more than 14 aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47 (95% CI, 0.31-0.71). A similar dose-response relationship was found for nonaspirin NSAIDs (P = .007 for trend). The incidence of reported major gastrointestinal bleeding events per 1000 person-years also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin tablets per week; 1.07 for 2 to 5 aspirin per week; 1.40 for 6 to 14 aspirin per week; and 1.57 for more than 14 aspirin per week. CONCLUSIONS: Regular, long-term aspirin use reduces risk of colorectal cancer. Nonaspirin NSAIDs appear to have a similar effect. However, a significant benefit of aspirin is not apparent until more than a decade of use, with maximal risk reduction at doses greater than 14 tablets per week. These results suggest that optimal chemoprevention for colorectal cancer requires long-term use of aspirin doses substantially higher than those recommended for prevention of cardiovascular disease, but the dose-related risk of gastrointestinal bleeding must also be considered.

Adult↗
PubMed2001

Profile and prevalence of aspirin resistance in patients with cardiovascular disease.

We determined the prevalence and clinical predictors of aspirin resistance by prospectively studying 325 patients with stable cardiovascular disease who were receiving aspirin (325 mg/day for > or =7 days) but no other antiplatelet agents. We also compared the detection of aspirin resistance with optical platelet aggregation, a widely accepted method, with a newer, more rapid method, the platelet function analyzer (PFA)-100, a whole blood test that measures platelet adhesion and aggregation ex vivo. Blood samples were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate (ADP) and arachidonic acid, and by PFA-100 using collagen and/or epinephrine and collagen and/or ADP cartridges to measure aperture closure time. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and a mean aggregation of > or =20% with 0.5 mg/ml arachidonic acid. Aspirin semiresponders were defined as meeting one, but not both of the above criteria. Aspirin resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time (< or =193 seconds). By optical aggregation, 5.5% of the patients were aspirin resistant and 23.8% were aspirin semiresponders. By PFA-100, 9.5% of patients were aspirin resistant. Of the 18 patients who were aspirin resistant by aggregation, 4 were also aspirin resistant by PFA-100. Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women (34.4% vs 17.3%, p = 0.001) and less likely to be smokers (0% vs 8.3%, p = 0.004) compared with aspirin-sensitive patients. There was a trend toward increased age in patients with aspirin resistance or aspirin semiresponders (65.7 vs 61.3 years, p = 0.06). There were no differences in aspirin sensitivity by race, diabetes, platelet count, renal disease, or liver disease.

Adult↗
PubMed2000

The effect of mini-dose aspirin on renal function and uric acid handling in elderly patients.

OBJECTIVE: Aspirin is known to have a bimodal effect on the renal handling of uric acid (UA). High dosages (>3 gm/day) are uricosuric, while low dosages (1-2 gm/day) cause UA retention. Although very-low-dose (mini-dose) aspirin is used increasingly as a platelet aggregation inhibitor, no studies have been published on whether aspirin's renal effects occur at dosages of <0.5 gm/day. The aim of the present study was to evaluate the effects of commonly used mini-dosages of aspirin on renal function and UA handling in elderly patients. METHODS: The study included 49 elderly inpatients (age 61-94). Patients were excluded if they had renal failure, hyperuricemia, gout, or a history of bleeding, or if they were receiving anticoagulants, aspirin, or nonsteroidal antiinflammatory drugs. Previous medications and diet were kept unchanged. Aspirin was administered as follows: 75 mg/day (week 1), 150 mg/day (week 2), 325 mg/day (week 3), and 0 mg/day (week 4). Baseline and weekly samples of blood and urine were evaluated for UA, creatinine, blood urea nitrogen, creatinine clearance, UA excretion, UA clearance, and plasma levels of aspirin. RESULTS: At the lowest dosage, aspirin caused a 15% decrease in the rate of UA excretion (P = 0.045 by t-test), which was associated with a slight but significant increase in serum levels of UA (P = 0.009). These effects on UA levels were gradually reduced with increasing dosages of aspirin (multivariate analysis of variance with repeated measures showed no statistically significant difference in the rate of UA excretion between weeks 1-3 and week 0 [baseline], but the difference in serum UA levels for the same comparison was statistically significant [P = 0.038]). Generally, creatinine and UA clearance rates paralleled each other during aspirin treatment. However, 1 week after aspirin was discontinued, creatinine clearance remained decreased while UA clearance returned to baseline. Plasma aspirin concentrations were low and variable. However, patients with above-median aspirin levels had significantly greater changes in serum creatinine levels, urinary UA excretion rates, and UA clearance rates following the first week of aspirin treatment. Hypoalbuminemia and concomitant treatment with diuretics enhanced the effects of aspirin on renal function and UA retention. CONCLUSION: Mini-dose aspirin, even at a dosage of 75 mg/day, caused significant changes in renal function and UA handling within 1 week in a group of elderly inpatients, mainly in those with preexisting hypoalbuminemia. Given the widespread (and often unmonitored) use of mini-dose aspirin, especially among the elderly, these findings call for clinician alertness as well as for further studies to clarify the mechanisms underlying these phenomena.

Age Factors↗
PubMed2002

Effects of non-steroidal anti-inflammatory drugs on cyclo-oxygenase and lipoxygenase activity in whole blood from aspirin-sensitive asthmatics vs healthy donors.

1. Cyclo-oxygenase (COX) and lipoxygenase (LO) share a common substrate, arachidonic acid. Aspirin and related drugs inhibit COX activity. In a subset of patients with asthma aspirin induces clinical symptoms associated with increased levels of certain LO products, a phenomenon known as aspirin-sensitive asthma. The pharmacological pathways regulating such responses are not known. 2. Here COX-1 and LO activity were measured respectively by the formation of thromboxane B(2) (TXB(2)) or leukotrienes (LT) C(4), D(4) and E(4) in whole blood stimulated with A23187. COX-2 activity was measured by the formation of prostaglandin E(2) (PGE(2)) in blood stimulated with lipopolysaccharide (LPS) for 18 h. 3. No differences in the levels of COX-1, COX-2 or LO products or the potency of drugs were found in blood from aspirin sensitive vs aspirin tolerant patients. Aspirin, indomethacin and nimesulide inhibited COX-1 activity, without altering LO activity. Indomethacin, nimesulide and the COX-2 selective inhibitor DFP [5,5-dimethyl-3-(2-isopropoxy)-4-(4-methanesulfonylphenyl)-2(5H)-furanone] inhibited COX-2 activity. NO-aspirin, like aspirin inhibited COX-1 activity in blood from both groups. However, NO-aspirin also reduced LO activity in the blood from both patient groups. Sodium salicylate was an ineffective inhibitor of COX-1, COX-2 or LO activity in blood from both aspirin-sensitive and tolerant patients. 4. Thus, when COX activity in the blood of aspirin-sensitive asthmatics is blocked there is no associated increase in LO products. Moreover, NO-aspirin, unlike other NSAIDs tested, inhibited LO activity in the blood from both aspirin sensitive and aspirin tolerant individuals. This suggests that NO-aspirin may be better tolerated than aspirin by aspirin-sensitive asthmatics.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Antiplatelet effect of aspirin in patients with cerebrovascular disease.

BACKGROUND AND PURPOSE: Aspirin is used commonly to prevent ischemic strokes and other vascular events. Although aspirin is considered safe and effective, it has limited efficacy with a relative risk reduction of 20% to 25% for ischemic stroke. We sought to determine if aspirin as currently used is having its desired antiplatelet effects. METHODS: We ascertained patients with cerebrovascular disease who were taking only aspirin as an antiplatelet agent. Platelet function was evaluated using a platelet function analyzer (PFA-100). PFA test results were correlated with aspirin dose, formulation, and basic demographic factors. RESULTS: We ascertained 129 patients, of whom 32% were taking an enteric-coated aspirin preparation and 32% were taking low-dose (< or =162 mg/d) aspirin. For the entire cohort, 37% of patients had normal PFA-100 results, indicating normal platelet function. For the patients taking low-dose aspirin, 56% had normal PFAs compared with 28% of those taking > or =325 mg/d of aspirin, while 65% of patients taking enteric-coated aspirin had normal PFAs compared with 25% taking an uncoated preparation (P<0.01 for both comparisons). Similar results were obtained if PFA results were analyzed using mean closure times (low-dose aspirin, 183 sec; high-dose aspirin, 233 sec; enteric-coated, 173 sec; uncoated, 235 sec; P<0.01 for comparisons). Older patients and women were less likely to have a therapeutic response to aspirin, independent of aspirin dose or formulation. CONCLUSIONS: A significant proportion of patients taking low-dose aspirin or enteric-coated aspirin have normal platelet function as measured by the PFA-100 test. If these results correlate with clinical events, they have broad implications in determining how aspirin is used and monitored.

Age Factors↗
PubMed1999

Prospective study of aspirin use and risk of stroke in women.

BACKGROUND AND PURPOSE: In secondary prevention, aspirin reduces risk of ischemic stroke. In primary prevention of stroke, however, the role of aspirin is uncertain, especially in women. METHODS: In 1980, 79 319 women in the Nurses' Health Study cohort, 34 to 59 years of age and free of diagnosed cardiovascular disease, cancer, and rheumatoid arthritis, completed questionnaires that included information on aspirin use. Data on aspirin use were updated in 1982, 1984, and 1988. By 1994, after 994 231 person-years of follow-up, 503 incident strokes (295 ischemic strokes, 100 subarachnoid hemorrhages, 52 intraparenchymal hemorrhages, and 56 strokes of undetermined type) were documented. RESULTS: There was no clear relationship between aspirin use and risk of total stroke; risk was slightly reduced among women who took 1 to 6 aspirin per week and slightly increased among women who took 7 or more aspirin per week. Women who took 1 to 6 aspirin per week had a lower risk of large-artery occlusive infarction compared with women who reported no aspirin use; after simultaneous adjustment for other cardiovascular risk factors and selected nutrients, the multivariate relative risk was 0.50 (95% CI 0.29 to 0.85, P=0.01). Women who took 15 or more aspirin per week had an excess risk of subarachnoid hemorrhage; the multivariate relative risk was 2.02 (95% CI 1.04 to 3.91, P for trend=0.02). The reduction in large-artery occlusive infarction with aspirin was of greater magnitude for older, hypertensive, or smoking women than for younger, nonhypertensive, or nonsmoking women; the elevation in subarachnoid hemorrhage with aspirin was also more apparent for older or hypertensive women than for younger or nonhypertensive women. Aspirin use was not associated with risk of other subtypes of stroke. CONCLUSIONS: These prospective data indicate that women who take 1 to 6 aspirin per week have a reduced risk of large-artery occlusive infarction, but those who use 15 or more aspirin per week have an increased risk of subarachnoid hemorrhage. This observational study suggests benefits of aspirin for ischemic stroke with low frequency of use and hazards for hemorrhagic stroke with high frequency of use, particularly among older or hypertensive women. Thus, the effect on total stroke will depend on the dose of aspirin and the distribution of stroke subtypes and risk factors in the population.

Adult↗
PubMed2007

Rapid desensitization protocols for patients with cardiovascular disease and aspirin hypersensitivity in an era of dual antiplatelet therapy.

OBJECTIVE: To review the available protocols for rapid desensitization of patients with aspirin hypersensitivity and apply the data for use in patients with cardiovascular disease who would benefit from the dual antiplatelet therapy. DATA SOURCES: A literature search was conducted via MEDLINE from 1966 to December 2006. Main search terms included: aspirin sensitivity, aspirin allergy, aspirin desensitization, aspirin-induced asthma, aspirin therapy, and aspirin intolerance syndrome. STUDY SELECTION AND DATA EXTRACTION: Articles describing rapid aspirin desensitization protocols were selected for review. Literature pertaining to aspirin hypersensitivity, drug desensitization, and the use of aspirin and dual antiplatelet therapy was also examined. Three rapid desensitization protocols were identified and evaluated. DATA SYNTHESIS: While landmark studies demonstrated that dual antiplatelet therapy with aspirin and clopidogrel significantly reduces mortality and morbidity in acute coronary syndromes and coronary stenting, patients with aspirin hypersensitivity are frequently managed with clopidogrel alone with no supporting data. Approximately 10% of the population experiences hypersensitivity to aspirin, which can manifest as asthma exacerbations, rhinorrhea, angioedema, urticaria, and anaphylaxis. The hypersensitivity reaction is mediated through aspirin-directed antibodies or by excessive leukotriene production. The desensitization process involved depletion of these mediators, as well as down-regulation of leukotriene receptors. Two groups of investigators developed rapid protocols to desensitize patients with aspirin hypersensitivity safely and effectively. The rapid protocol developed by Wong provides benefits over other protocols with its low starting dose and completion in less than 3 hours, low incidence of adverse effects, and high success rate in aspirin desensitization. CONCLUSIONS: The Wong protocol is an attractive option for the rapid desensitization of patients requiring dual antiplatelet therapy with aspirin and clopidogrel in the perimyocardial infarction period.

Aspirin↗
PubMed2004

A prospective audit of blood loss and blood transfusion in patients undergoing coronary artery bypass grafting after clopidogrel and aspirin therapy.

OBJECTIVE: Platelet dysfunction is a common cause of bleeding after coronary artery bypass graft (CAG) surgery. This prospective observational audit explored the effects of clopidogrel and aspirin on chest drain output for the first 24 hours after CAG surgery. METHODS: During a 7 week period from July to Aug 2003, all patients who underwent CAG at the London Chest Hospital were audited. Patients undergoing concomitant valvular surgery were excluded. The study population included patients who had previous cardiac surgery and patients undergoing emergency procedures. Patients were sub-divided into those who were exposed within 7 days of surgery to clopidogrel alone, aspirin alone, both aspirin and clopidogrel and those not exposed to either agent. RESULTS: During the study period, 91 patients were audited. Two patients were excluded due to concomitant valvular surgery. The remaining 89 patients, included those who were exposed within 7 days of surgery to clopidogrel alone (n = 2 ), both aspirin and clopidogrel (n = 12), aspirin alone (n = 65) and those not exposed to either agent (n = 10). The groups were comparable in age, gender, body weight and baseline haematocrit. The clopidogrel and aspirin group had a lower mean chest drain output at 24 hours post CAG compared with both the aspirin alone and non-clopidogrel non-aspirin groups (694.4 mL vs. 831.9 mL vs. 726 mL), although these differences were not statistically significant. Both the clopidogrel-with-aspirin and the aspirin-only groups received blood products more frequently when compared with the non-clopidogrel non-aspirin group and also the mean number of units transfused per patient was greater. Consistent with the highest mean blood loss, the aspirin group was transfused more units of blood than the clopidogrel and aspirin group and non-clopidogrel non aspirin groups (1.67 vs. 1.0 vs. 0.6 units of blood) Again, these differences were not statistically significant. Nevertheless, overall, the frequency and amount of blood transfusion in those patients who were not receiving aspirin or clopidogrel preoperatively was lower than for those receiving clopidogrel and/or aspirin. CONCLUSIONS: Our audit suggested that continuing to administer clopidogrel and/or aspirin in the 7 days prior to CAG surgery is associated with higher postoperative bleeding and morbidity. However, this increased bleeding tendency did not appear to result in a clinically significant increased requirement for allogenic blood product transfusion.

Journal Article↗
PubMed2006

Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers.

BACKGROUND AND PURPOSE: Aspirin resistance may be relatively common and associated with adverse outcome. Meta-analysis has clearly shown that 75 mg plain aspirin is the lowest effective dose; however, it is not known whether the recent increased use of enteric-coated aspirin could account for aspirin resistance. This study was designed to determine whether enteric-coated aspirin is as effective as plain aspirin in healthy volunteers. METHODS: Seventy-one healthy volunteers were enrolled in 3 separate bioequivalence studies. Using a crossover design, each volunteer took 2 different aspirin preparations. Five aspirin preparations were evaluated, 3 different enteric-coated 75-mg aspirins, dispersible aspirin 75 mg and asasantin (25-mg standard release aspirin plus 200-mg modified-release dipyridamole given twice daily). Serum thromboxane (TX) B2 levels and arachidonic acid-induced platelet aggregation were measured before and after 14 days of treatment. RESULTS: All other aspirin preparations tested were inferior to dispersible aspirin (P<0.001) in their effect on serum TXB(2) level. Treatment failure (<95% inhibition serum TXB2 formation) occurred in 14 subjects, none of whom were taking dispersible aspirin. Mean weight for those demonstrating treatment failure was greater than those with complete TXB2 (>99%) inhibition (P<0.001). Using logistic regression analysis an 80-kg subject had a 20% probability of treatment failure. Asasantin was the most potent preparation in terms of inhibition of platelet aggregation. CONCLUSIONS: Equivalent doses of the enteric-coated aspirin were not as effective as plain aspirin. Lower bioavailability of these preparations and poor absorption from the higher pH environment of the small intestine may result in inadequate platelet inhibition, particularly in heavier subjects.

Adult↗
PubMed1997

Does daily aspirin diminish severity of first-ever stroke?

BACKGROUND: There are still uncertainties about aspirin efficacy in first-ever ischemic stroke prevention. Also it is unknown whether the severity of first ischemic stroke can be modified by aspirin pretreatment. OBJECTIVE: To analyze a series of patients who had their first ischemic stroke while taking aspirin to evaluate the ability of aspirin prophylaxis to diminish the severity of first-ever ischemic stroke. DESIGN: Case-control study. SETTING: Tertiary medical center to which patients were referred. PATIENTS: All consecutive patients admitted to the Tel Aviv Medical Center, Tel Aviv, Israel, from May 1988 through May 1994 because of first-ever ischemic stroke were divided into 2 groups according to aspirin use before stroke: aspirin-treated and non-aspirin-treated groups. MAIN OUTCOME MEASURES: Stroke severity was defined according to activities of daily living within 24 hours after admission: (1) mild stroke, with independence in activities of daily living; (2) moderate stroke, with partial dependency; and (3) severe stroke, with complete dependency. Using chi 2 test, stroke severity was compared between patients taking aspirin before their stroke and non-aspirin-treated patients. RESULTS: Among 2113 consecutive patients with first-ever ischemic stroke, 125 patients had already been taking 100 to 500 mg of aspirin daily. Aspirin-treated and non-aspirin-treated patients did not differ in stroke severity. Mortality was lower in aspirin-treated patients (7.9%) than in non-aspirin-treated patients (12%), but this difference was not statistically significant (P = 17). CONCLUSIONS: We conclude that aspirin as primary prevention treatment has no significant protective effect on severity of first-ever ischemic stroke. The diminution of mortality after first ischemic stroke in patients who had used aspirin should be investigated further.

Aged↗
PubMed2006

Aspirin failure course during exercise and its connection with soluble CD40L.

INTRODUCTION: The aspirin failure (resistance) is a still discussed and highly studied problem. This phenomenon is observed in rest, but could be precipitated by an exercise. The aspirin resistance was also linked with the inflammatory process which is a key event for the atherosclerosis development. Platelets seem to play an important role also in that setting, probably by the CD40-CD40L axis. The aim of the study was to assess the frequency of the aspirin failure induced by the exercise and the role of sCD40L in that regard. MATERIALS AND METHODS: The study included 40 patients with established coronary artery disease. The control group consisted of 10 patients without coronary artery disease matched for age. All patients and controls were on 75 mg of aspirin for at least 30 days and had treadmill testing and blood collected for measurement of sCD40L and optical platelet aggregation with ADP, collagen and arachidonic acid. Aspirin resistance was defined as a maximal aggregation with ADP and collagen exceeding 70%. RESULTS: There were 15 aspirin-resistant patients in the studied group (37%). There were significantly higher concentration of sCD40L (ng/ml) in aspirin-resistant patients in comparison with aspirin-sensitive ones before testing (7,9 +/- 2,5 vs. 5,1 +/- 3,5, p < 0,05) and on the top of it (8,1 +/- 2,9 vs. 4,5 +/- 3,9, p < 0,05). There were 3 persons who become resistant on the top of the exercise which was connected with the significant increase of sCD40L concentration in that group (from 7,6 +/- 1,9 before exercise to 10,1 +/- 2,9 on the top of the exercise, p < 0,05). There was also a positive correlation between the sCD40L level before and on the top of the exercise in an aspirin-resistant group (r = 0,48 for both, p < 0,05). Patients who were aspirin-resistant at rest had also significant elevation of platelet aggregation on the top of the exercise (ADP (%) from 90,5 +/- 8,6 to 95,0 +/- 6,5, p < 0,05 and collagen (%) from 87,8 +/- 8,7 to 92,1 +/- 8,0, p < 0,05). CONCLUSIONS: 1. Aspirin resistance phenomenon is present in about 37% patients on 75 mg aspirin daily.2. Aspirin-resistant patients have higher platelet aggregation during the exercise.3. Moderate physical exercise provokes 12% increase in the aspirin resistance phenomenon occurrence.4. Aspirin resistance is connected with higher sCD40L level at rest and exercise provoked aspirin resistance is connected with the sCD40L concentration increase.

Aged↗
PubMed2006

Variation and importance of aspirin resistance in patients with known cardiovascular disease.

AIM: To investigate whether aspirin resistance is a persistent condition, and to evaluate if aspirin resistance affects one-year clinical outcome. METHODS AND RESULTS: Previously we studied 298 patients admitted to hospital with symptoms suggestive of an acute myocardial infarction (MI) despite treatment with aspirin, and 70 patients (23.5%) were aspirin resistant. In the present study, platelet function was reassessed by use of a Platelet Function Analyzer-100 one year later. A total of 187 patients were re-examined, and 17 (9.1%) demonstrated aspirin resistance. Of these 17 patients, 12 also exhibited aspirin resistance at baseline resulting in a 6% (12/187) prevalence of persistent aspirin resistance. A total of 34 patients had changed from aspirin resistant at baseline to aspirin sensitive at follow-up. We found a significant decrease in the prevalence of aspirin resistance from baseline (43%) to follow-up (11%) in patients with MI at baseline (p=0.0018). Furthermore, a significant decrease was found for patients without MI at baseline (20% to 9%, p=0.0009). During follow-up, 17% (12/70) of the patients with aspirin resistance at baseline suffered death, MI or stroke compared to 16% (37/227) of aspirin sensitive patients (p=0.868). CONCLUSION: The prevalence of aspirin resistance varies with the clinical status of the patients, and indeed an acute MI is associated with temporary aspirin resistance. We also found that 6% of patients demonstrate persistent aspirin resistance. The presence of aspirin resistance did not affect one-year clinical outcome.

Aged↗
PubMed1988

Influence of antacid administrations on aspirin absorption in patients with chronic renal failure on maintenance hemodialysis.

In order to investigate the possible interaction between oral aspirin and antacids in uremic patients on chronic hemodialysis, we administered to 5 uremic patients: (1) aspirin alone; (2) aluminum-magnesium hydroxide with aspirin; (3) aluminum-magnesium hydroxide followed (two hours) by aspirin; (4) calcium carbonate simultaneously with aspirin; and (5) calcium carbonate followed (two hours) by aspirin. In all the occasions, aspirin was given two hours after a standard lunch. Both antacid preparations induced comparable changes in aspirin mean peak plasma concentration (Cmax), if given simultaneously with aspirin, whereas no difference was found in other pharmacokinetic parameters. When antacids were followed (two hours) by aspirin, both Cmax and time of maximum concentration (Tmax) were significantly altered in respect to the value with aspirin alone. No changes in the time course of post aspirin serum thromboxane B2 were detected when aspirin and antacids were administered simultaneously, but the inhibition of serum thromboxane B2 was delayed when antacids were followed (two hours) by aspirin. These results indicate that the administration of antacids to uremic patients interferes with absorption of oral aspirin. This interference can be minimized if aspirin and antacids are given simultaneously.

Absorption↗
PubMed2004

Ulcer formation with low-dose enteric-coated aspirin and the effect of COX-2 selective inhibition: a double-blind trial.

BACKGROUND & AIMS: We assessed the risk of ulcers with low-dose aspirin and the interaction of low-dose aspirin with a COX-2 selective inhibitor in a double-blind trial that compared placebo, low-dose aspirin, rofecoxib + low-dose aspirin, and ibuprofen. METHODS: Osteoarthritis patients > or =50 years of age without ulcers or erosive esophagitis at baseline endoscopy were assigned randomly to placebo, enteric-coated aspirin 81 mg/day, rofecoxib 25 mg combined with aspirin 81 mg/day, or ibuprofen 800 mg 3 times a day. Repeat endoscopies were performed at 6 and 12 weeks. RESULTS: The 12-week cumulative incidence of ulcers was placebo (N = 381) 5.8%, aspirin (N = 387) 7.3%, rofecoxib combined with aspirin (N = 377) 16.1%, and ibuprofen (N = 374) 17.1% (P < 0.001 for rofecoxib combined with aspirin and for ibuprofen vs. each of placebo and aspirin). Over 12 weeks, mean increases in the number of erosions were placebo 0.17, aspirin 0.85 (P = 0.002 vs. placebo), rofecoxib combined with aspirin 1.67, and ibuprofen 1.91 (both P < 0.001 vs. aspirin and placebo). CONCLUSIONS: Low-dose aspirin alone did not significantly increase ulcer incidence. Addition of a cyclooxygenase-2 (COX-2) selective inhibitor to low-dose aspirin increased ulcer incidence, to a rate not significantly less than a nonselective nonsteroidal anti-inflammatory drug (NSAID) alone. Determining the relative impact of COX-2 selective inhibitors and nonselective NSAIDs on gastrointestinal mucosal injury in low-dose aspirin users will require further study.

Aged↗
PubMed2005

Assessment of the antiplatelet effects of low to medium dose aspirin in the early and late phases after ischaemic stroke and TIA.

Vascular events commonly recur in stroke patients on aspirin, and may reflect incomplete inhibition of platelet function with aspirin therapy. The platelet function analyser (PFA-100) activates platelets by aspirating a blood sample at a moderately high shear rate through a capillary to a biologically active membrane with a central aperture. The membrane is coated with collagen, and either ADP (C-ADP) or epinephrine (C-EPI). The time taken for activated platelets to adhere, aggregate, and occlude the aperture is called the closure time. Previous studies have shown that aspirin prolongs the C-EPI closure time, without prolongation of the C-ADP closure time, in the majority of control subjects. We hypothesised that the PFA-100 would provide a sensitive assay for the detection of early and convalescent phase cerebrovascular disease (CVD) patients who had incomplete inhibition of platelet function with aspirin. We investigated potential cyclooxygenase-dependent and -independent mechanisms that might influence the responsiveness to aspirin using the PFA-100. Patients were studied during the early (< or = 4 weeks, n=57) and convalescent phases ((< or = 3 months, n=46) after ischaemic stroke or TIA. To investigate potential mechanisms that could contribute to aspirin responsiveness on the PFA-100, we measured von Willebrand factor antigen levels, and carried out platelet aggregometry experiments in platelet-rich plasma in response to sodium arachidonate (1 mM) and ADP (5 microM). Sixty percent of patients in the early phase and 43% of patients in the convalescent phase did not have prolonged C-EPI closure times on 75-300 mg of aspirin daily, and were defined as aspirin non-responders. Median C-ADP closure times were significantly shorter in aspirin non-responders than aspirin-responders in both the early and convalescent phases after symptom onset (P=0.008), suggesting platelet hyper-reactivity to collagen or ADP in the aspirin non-responder subgroup. There was a significant inverse relationship between plasma von Willebrand factor antigen levels and C-EPI closure times in both early and convalescent phase CVD patients (P=0.008). Mean von Willebrand factor antigen levels were significantly higher in aspirin non-responders than aspirin responsive patients in the early (P=0.001), but not convalescent phase (P=0.2) after stroke and TIA. None of the patients studied were defined as being aspirin-resistant using sodium arachidonate- or ADP-induced platelet aggregometry. A large proportion of ischaemic CVD patients have incomplete inhibition of platelet function with low to medium dose aspirin using the PFA-100. The results suggest that cyclooxygenase-independent mechanisms, including elevated von Willebrand factor antigen levels, play an important role in mediating aspirin non-responsiveness on the PFA-100.

Adenosine Diphosphate↗
PubMed1993

Low-dose aspirin and incidence of colorectal tumors in a randomized trial.

BACKGROUND: Laboratory, clinical, and epidemiologic studies have recently suggested that regular use of aspirin can reduce colorectal cancer incidence or mortality. However, observational epidemiologic analyses have had limited opportunity to control for confounding bias or to specify aspirin doses used. PURPOSE: Our purpose was to examine the relationship between regular use of low-dose aspirin and incidence of invasive and noninvasive colorectal tumors by utilizing data from the Physicians' Health Study, a randomized, double-blinded, placebo-controlled trial of aspirin and beta carotene. We also attempted to determine whether invasive cancers among aspirin users were associated with rectal bleeding and early stage at diagnosis. METHODS: The Physicians' Health Study includes 22071 U.S. male physicians. The aspirin arm was terminated in 1988 after a mean follow-up of 5 years. Stage at diagnosis and signs and/or symptoms during presentation were abstracted from medical records. Cox proportional hazards models were used to estimate relative risk (RR), 95% confidence intervals (CIs), and the association between aspirin and bleeding. Differences between aspirin and placebo groups in tumor risk over time were visualized with Kaplan-Meier curves. We assessed the association between aspirin and stage at diagnosis with a Mann-Whitney rank sum statistic for non-parametric comparison of two ordinal distributions. RESULTS: The RR of developing colorectal cancer for aspirin compared with placebo was 1.15 (95% CI = 0.80-1.65). For in situ cancers and polyps, the RR was 0.86 (95% CI = 0.68-1.10). There was no significant trend for decreasing RR by year of follow-up for invasive cancers (P = .09) or noninvasive tumors (P = .96). Aspirin and placebo groups did not differ in stage or prevalence of rectal bleeding at diagnosis. CONCLUSIONS: Regular aspirin use, at a dose adequate for preventing myocardial infarction, was not associated with a substantial reduction in the incidence of colorectal cancer during 5 years of randomized treatment and follow-up. A small decrease in polyps in the aspirin group could not be reliably distinguished from a chance association. Our results suggest that among low-dose aspirin users, (a) colorectal cancer mortality is not likely to be reduced by earlier detection and (b) incidence is not likely to be increased due to aspirin-induced gastrointestinal bleeding. IMPLICATIONS: The potential for a benefit from higher doses of aspirin or longer duration of use should be addressed by more detailed observational epidemiologic studies and prevention trials with longer follow-up of randomized participants.

Adult↗
PubMed1975

The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein.

Aspirin (acetylsalicylic acid) inhibits platelet prostaglandin synthesis and the ADP- and collagen-induced platelet release reaction. The mechanism of the inhibitory effect is unknown but may involve protein acetylation, since aspirin acetylates a variety of substrates, including platelet protein. We have examined the relationship between protein acetylation and aspirin's physiologic effect on platelets. Suspensions of washed human platelets were incubated at 37 degrees C with (3H)aspirin, and incorporation of radioactivity into protein was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Exposure to (acetyl-3H)aspirin but not (aromatic ring-3H)aspirin resulted in radioactive labeling of three platelet proteins, suggesting that the drug acetylates these three proteins. The acetylation of two of the proteins (located in the supernatant fraction) was not saturable, implying that these reactions may not be physiologically significant. Acetylation of the third protein, approximate mol wt 85,000 (located in the particulate fraction), saturated at an aspirin concentration of 30 muM and was complete within 20 min. Platelets prepared from aspirin-treated donors did not incorporate any (acetyl-3H)aspirin radioactivity into the particulate protein for 2 days after drug treatment and did not show full pretreatment uptake of radioactivity for 12 days thereafter. The course of increasing incorporation of (acetyl-3H)aspirin radioactivity parralleled that of platelet turnover. Therefore, in addition to its saturability, acetylation of the particulate fraction protein by aspirin was permanent. In two respects, the inhibition of platelet function by aspirin correlates well with the aspirin-mediated acetylation of the particulate fraction protein. Both persist for the life-span of the aspirin-treated platelet, and both occur at a similar saturating aspirin concentration. The evidence suggests that the physiologic effect of aspirin on human platelets is produced by acetylation of a single protein located in the particulate fraction. The acetylated protein may be related to cyclo-oxygenase, the prostaglandin G2 biosynthetic enzyme.

Acetates↗
PubMed2004

Failure of aspirin to prevent atherothrombosis: potential mechanisms and implications for clinical practice.

Aspirin (acetylsalicylic acid) reduces the odds of serious atherothrombotic vascular events and death in a broad category of high risk patients by about one-quarter. The mechanism is believed to be inhibition of thromboxane biosynthesis by inactivation of platelet cyclo-oxygenase-1 enzyme. However, aspirin is not that effective; it still fails to prevent the majority of serious vascular events. Mechanisms that may account for the failure of aspirin to prevent vascular events include non-atherothrombotic causes of vascular disease, non-adherence to aspirin therapy, an inadequate dosage, alternative "upstream" pathways of platelet activation (e.g. via stimulation of the ADP, collagen or thrombin receptors on platelets), aspirin-insensitive thromboxane biosynthesis (e.g. via monocyte cyclo-oxygenase-2), or drugs that interfere with the antiplatelet effects of aspirin. Genetic or acquired factors may further modify the inhibitory effects of aspirin on platelets (e.g. polymorphisms involving platelet-associated proteins, increased platelet turnover states). Identification and treatment of the potential causes of aspirin failure could prevent at least another 20% of serious vascular events (i.e. over and above those that are currently prevented by aspirin). There is currently no role for routine laboratory testing to measure the antiplatelet effects of aspirin. Clinicians should ensure that patients at high risk of atherothrombosis (>3% risk over 5 years) are compliant with aspirin therapy and are taking the correct dosage (75-150 mg/day). Patients who cannot tolerate aspirin, are allergic to aspirin, or have experienced recurrent serious atherothrombotic events whilst taking aspirin, should be treated with clopidogrel, and patients with acute coronary syndromes benefit from the combination of clopidogrel plus aspirin. Future research is required to standardize and validate laboratory testing of the antiplatelet effects of aspirin and to identify treatments that can both improve these laboratory measures and reduce the risk of future atherothrombotic events.

Aspirin↗