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PubMed2004

Cost-effectiveness of aspirin chemoprevention for Barrett's esophagus.

BACKGROUND: Recent data suggest that nonsteroidal anti-inflammatory drugs, including aspirin, may prevent the progression of Barrett's esophagus to adenocarcinoma. However, use of aspirin is associated with numerous potential complications, including gastrointestinal bleeding and hemorrhagic strokes. We used a modeling approach to determine and compare the effectiveness and cost-effectiveness of aspirin with and without endoscopic surveillance to prevent esophageal adenocarcinoma. METHODS: A Markov Monte Carlo decision model was constructed to compare four strategies for management of Barrett's esophagus: aspirin therapy, endoscopic surveillance with biopsies, both, or neither. Patients who took a daily enteric-coated aspirin were modeled to have a 50% reduction in the incidence of esophageal adenocarcinoma but could have complications related to therapy, at which point the aspirin was discontinued. Potential cardiac benefits of aspirin and its role in the chemoprevention of other cancers were not included in the analysis. The analysis was from a societal perspective from age 55 years until death. Sensitivity analyses were performed to investigate the effects of changes in model parameters on estimated costs and effectiveness outcomes across a wide range of assumptions. RESULTS: Aspirin therapy was more effective and less costly than no therapy, resulting in 0.19 more quality-adjusted life years (QALYs). The combination of aspirin and endoscopic surveillance produced 0.27 more QALYs than no therapy at a cost of 13,400 U.S. dollars more, for an associated incremental cost-effectiveness ratio of 49,600 U.S. dollars/QALY. Aspirin use in combination with endoscopic surveillance dominated endoscopic surveillance alone, resulting in 0.06 more QALYs and 11,400 U.S. dollars less cost. The model's results were sensitive to increasing age and to decreased benefit or delay in aspirin's chemopreventive efficacy. CONCLUSION: Using published values of parameters, regardless of whether a patient undergoes endoscopic surveillance, aspirin use in the management of Barrett's esophagus appears to be a cost-effective strategy to prevent esophageal adenocarcinoma.

Aged↗

PubMed1993

Clinical efficacy of aspirin and dextran for thromboprophylaxis in geriatric hip fracture patients.

The clinical efficacy of thromboprophylaxis with aspirin and dextran 40 was compared in a prospective review of 530 geriatric hip fracture patients treated surgically. All patients were also treated with early mobilization with weight bearing as tolerated and above-knee elastic stockings. In addition to clinical efficacy in preventing thromboembolic complications [deep vein thrombosis (DVT), pulmonary embolism (PE)], safety and cost-effectiveness were also assessed. The overall incidence of clinical thromboembolic disease was 2.8% (DVT = 0.4%, PE = 2.4%). The incidence of DVT (0.5%) and PE (2.6%) in the aspirin group was essentially the same as the incidence of DVT (0.3%) and PE (2.4%) in the dextran group. The inhospital mortality rate (aspirin 4.6%, dextran 3.8%), wound drainage (aspirin 1.5%, dextran 0.9%), deep wound infection (aspirin 0.5%, dextran 0.3%), gastrointestinal bleeding (aspirin 2.1%, dextran 1.5%), and congestive heart failure (aspirin 2.6%, dextran 1.8%) did not differ significantly between the two groups. The intraoperative transfusion rate was similar in both groups (aspirin .65 units, dextran .55 units). However, postoperatively, the transfusion rate was significantly higher in the dextran group (aspirin .26 units, dextran .41 units, p < .05). The treatment of thromboembolic complications was the same for each group and therefore represents similar treatment costs. However, the cost of prophylaxis with dextran was $309 per patient and with aspirin was $1.79 per patient. Our findings suggest that, based on clinical diagnostic criteria, aspirin and dextran are equally effective thromboembolic prophylactic agents in geriatric hip fracture patients. The safety, cost, and ease of administration of aspirin may make its use more desirable.

Aged↗

PubMed2006

Aspirin resistance: is this term meaningful?

PURPOSE OF REVIEW: To review data for and against the existence of 'aspirin resistance', a term coined to indicate aspirin-treated patients having ex-vivo tests of platelet activation insensitive to aspirin treatment and recurrence of cardiovascular disease. RECENT FINDINGS: 'Aspirin resistance' defined by ex-vivo tests of platelet activation yielded values ranging from 21 to 78%, indicating that such tests do not provide a useful measurement. In long-term aspirin-treated patients, studies demonstrated small but functionally relevant platelet thromboxane A2 formation that was responsible for an enhanced platelet activation in response to platelet agonist. These studies, however, did not fully exclude that aspirin compliance may be implicated in such phenomena. Two trials performed in patients with coronary artery disease demonstrated that laboratory evidence of aspirin resistance was no longer detectable when aspirin compliance was accurately monitored. SUMMARY: Given the multifactorial nature of atherothrombosis, recurrence of cardiovascular events in aspirin-treated patients does not necessarily suggest 'drug failure'. A cause-effect relationship between platelet insensitivity to aspirin and cardiovascular recurrence has not been defined overall because aspirin compliance has been scarcely considered. Until this information is taken into account, the existence of 'clinical resistance' to aspirin should be reconsidered.

Aspirin↗

PubMed2007

Assessment of biochemical aspirin resistance at rest and immediately after exercise testing.

Some aspirin-treated patients experience thromboembolic events, a phenomenon termed 'aspirin resistance', which may be clinical or biochemical by definition. Physical exercise is known to enhance platelet secretion and aggregability. To evaluate the presence of biochemical aspirin resistance at rest and immediately after exercise in individuals with stable coronary artery disease or coronary artery disease risk factors. We prospectively enrolled 101 patients who had received 100 or 300 mg/day enteric-coated aspirin for at least 7 days. Biochemical aspirin resistance (defined as normal collagen-epinephrine closure time < 165 s) was studied using the standardized platelet function analyzer. Of the 101 patients, 63 were aspirin sensitive both at rest and immediately after exercise, 18 exhibited biochemical aspirin resistance both at rest and after exercise, and 20 were aspirin sensitive at rest but exhibited biochemical aspirin resistance immediately after exercise. The results of exercise testing were similar in all three groups (each P > 0.05). Our results indicate that in almost 20% of the patients, aspirin did not seem to protect against exercise-induced platelet activation, despite the presence of aspirin sensitivity at rest. We did not, however, determine the extent to which the biochemical aspirin resistance noted in our study applied to clinical events.

Aged↗

PubMed2005

The human leucocyte antigen-DRB11302-DQB10609-DPB1*0201 haplotype may be a strong genetic marker for aspirin-induced urticaria.

BACKGROUND: Urticaria/angioedema is a common aspirin-induced allergy; however, its pathogenic mechanism is not understood. OBJECTIVE: In order to uncover the genetic mechanism, we studied the associations of the human leucocyte antigen (HLA) genotypes in patients with aspirin-induced urticaria compared with aspirin-intolerant asthma and normal control in a Korean population. METHODS: Ninety-four aspirin-induced urticaria patients presenting urticaria/angioedema-induced by both ASA and NSAID (50 had underlying chronic urticaria) and showing positive responses on oral aspirin challenge test, 76 aspirin-intolerant asthmatics with positive responses on lysine-aspirin bronchoprovocation test, and 185 normal healthy controls were enrolled. HLA-DRB1, DQB1, and DPB1 genotypings were performed by direct DNA sequencing analysis. RESULTS: The allele frequencies of HLA-DRB1(*)1302 (18.1%) and HLA-DQB1(*)0609 (10.1%) in aspirin-induced urticaria were significantly higher than in aspirin-intolerant asthma (5.3%, P=0.0004; 2.0%, P=0.0024) and in normal controls (8.1%, P=0.0005; 3.2%, P=0.0008), and they remained significant after correcting for multiple comparisons. The patients with these two HLA markers had a significantly younger age than patients without, while no associations were found in with respect to atopic status, a history of previous allergic diseases, total IgE level, or presence of underlying chronic urticaria (P>0.05, respectively). In haplotype analysis, the HLA-DRB1(*)1302-DQB1(*)0609-DPB1(*)0201 was significantly higher in the aspirin-induced urticaria (8.0%) than in the aspirin-intolerant asthma (0.7%, P=0.0014) and normal controls (2.0%, P=0.0006). CONCLUSION: These findings suggest that the HLA-DRB1(*)1302-DQB1(*)0609-DPB1(*)0201 may be a strong genetic marker to determine the aspirin-induced urticaria phenotype.

Adult↗

PubMed1990

Selective inhibition of platelet cyclooxygenase with controlled release, low-dose aspirin.

The hypothesis that slow administration of low doses of aspirin may selectively inhibit platelet cyclooxygenase and thromboxane A2 formation was evaluated using controlled release aspirin formulations. In the first study, doses of either 50, 100, 325 and 1,300 mg of these formulations and 300 mg soluble aspirin were ingested daily by healthy volunteers for one week. In the second study, doses of 5, 10, 25 and 50 mg controlled release aspirin, 50 mg soluble aspirin and 100 mg aspirin and glycine formulation were ingested daily for ten days. Platelet function and urinary prostaglandin production were assessed immediately before and on the seventh day of dosing in both studies and in the second study, repeated on the tenth day of dosing. Platelet function and serum thromboxane B2 production were fully inhibited by all formulations of 50 mg aspirin and above, but not by doses of controlled release aspirin below 50 mg doses. The excretion of urinary 6-keto-PGF1 alpha (a major metabolite of prostacyclin) was significantly reduced at controlled release aspirin doses above 100 mg and at all doses of rapidly absorbed aspirin tested. As no significant reduction in the urinary 6-keto-PGF1 alpha production was observed at doses of controlled release aspirin of 50 and 100 mg and below, it appeared that these doses did not inhibit the systemic vascular cyclooxygenase. These data are consistent with a selective inhibition of platelet function by daily doses of 50 and 100 mg of the controlled release formulation of aspirin.

6-Ketoprostaglandin F1 alpha↗

PubMed2006

Biological effects of aspirin and clopidogrel in a randomized cross-over study in 96 healthy volunteers.

BACKGROUND: Some data suggest that biological 'resistance' to aspirin or clopidogrel may influence clinical outcome. OBJECTIVE: The aim of this study was to evaluate the relationship between aspirin and clopidogrel responsiveness in healthy subjects. METHODS: Ninety-six healthy subjects were randomly assigned to receive a 1-week course of aspirin 100 mg day(-1) followed by a 1-week course of clopidogrel (300 mg on day 1, then 75 mg day(-1)), or the reverse sequence, separated by a 2-week wash-out period. The drug effects were assessed by means of serum TxB2 assay, platelet aggregation tests, and the PFA -100 and Ultegra RPFA -Verify Now methods. RESULTS: Only one subject had true aspirin resistance, defined as a serum TxB2 level > 80 pg microL(-1) at the end of aspirin administration and confirmed by platelet incubation with aspirin. PFA-100 values were normal in 29% of the subjects after aspirin intake, despite a drastic reduction in TxB2 production; these subjects were considered to have aspirin pseudo-resistance. Clopidogrel responsiveness was not related to aspirin pseudo-resistance. Selected polymorphisms of platelet receptor genes were not associated with either aspirin or clopidogrel responsiveness. CONCLUSIONS: In healthy subjects, true aspirin resistance is rare and aspirin pseudo-resistance is not related to clopidogrel responsiveness.

Adolescent↗

PubMed1993

Influence of aspirin on human megakaryocyte prostaglandin synthesis.

To evaluate whether currently popular aspirin regimens have an effect on the prostaglandin synthesis in human megakaryocytes we measured thromboxane B2 (TXB2) synthesis in response to thrombin stimulation in human megakaryocytes ex vivo. Human megakaryocytes were purified by Counterflow Centrifugal Elutriation from bone marrow punctures, taken from volunteers before and 2 hours after ingestion of one dose of 500 mg (n = 4), 80 mg (n = 4) or 40 mg (n = 2) aspirin. Subsequently, megakaryocytes were purified before and 12 h after ingestion of 80 mg (n = 3) aspirin twice daily for 1 week and 12 h after 500 mg (n = 3) aspirin. On average, 140 +/- 102 x 10(3) (mean +/- 1 SD) megakaryocytes were recovered. We found that aspirin inhibits megakaryocyte cyclooxygenase in a dose-dependent manner. Two hours after 500 mg of aspirin, TXB2 synthesis in megakaryocytes was inhibited by 96.8 +/- 2%, whereas one dose of 80 and 40 mg aspirin showed an inhibition of 79.4 +/- 13.7% and 80 +/- 6.2% respectively. However, the inhibition of TXB2 synthesis seems not to be long-lasting since, 12 h after the ingestion of aspirin, an increase of megakaryocyte TXB2 production could be observed which reached significance after the 500 mg aspirin dosage (p < 0.048). We conclude that human megakaryocyte cyclooxygenase is sensitive to aspirin inhibition and that low doses of aspirin (40 and 80 mg) enter the systemic circulation and are able to inhibit megakaryocyte cyclooxygenase, but this inhibition is incomplete and megakaryocyte cyclooxygenase seems to recover within 12 h after ingestion of aspirin.

Aspirin↗

PubMedDate not supplied

Effects of cutaneous aspirin on the human stomach and duodenum.

Oral aspirin blocks cyclooxygenase in platelets, lowering serum thromboxane concentrations. Oral aspirin also blocks cyclooxygenase in the gastrointestinal mucosa, lowering prostaglandin production and increasing the risk of gastrointestinal ulceration and bleeding. Aspirin placed on the skin also inhibits cyclooxygenase in platelets, but aspirin absorption through skin is slow, which may minimize the gastrointestinal effects. Our objectives in this study were 1) to compare the pharmacokinetic and pharmacodynamic effects of cutaneous and oral aspirin in healthy volunteers and 2) to compare the effects of cutaneous aspirin on gastroduodenal mucosal prostaglandin E2 and F2 alpha content and on mucosal damage, using endoscopy. The bioavailability of cutaneous aspirin was 4%-8% that of oral aspirin. Cutaneous aspirin (750 mg/day for 10 days) significantly lowered serum thromboxane (by 85%) and gastric and duodenal prostaglandins (by 49%-71%); placebo had no effect. Moreover, cutaneous aspirin, but not placebo, resulted in significant gastric mucosal injury. These findings demonstrate that even tiny amounts of aspirin in the blood (2 microM) have inhibitory effects on prostaglandin production in the human stomach and duodenum that result in gastric mucosal damage, even without direct exposure of the stomach to aspirin.

Administration, Cutaneous↗

PubMed1999

Effects of aspirin on psychophysical measures of frequency selectivity, two-tone suppression, and growth of masking.

Three psychophysical measures of nonlinearity were evaluated before and during a course of aspirin ingestion to investigate the role of outer hair cells (OHCs) in these measures, as aspirin is thought to alter the functioning of OHCs. Six normal-hearing individuals received a moderate dose (3.9 g/day) of aspirin for four days, producing essentially flat, temporary hearing losses that ranged from 5-20 dB. The losses were about 2 dB greater for a 300-ms signal than for a 15-ms signal, indicating reduced temporal integration with aspirin. On the final three days of aspirin use, three experiments were completed; each was designed to measure one aspect of nonlinear behavior: (1) the effects of level on frequency selectivity in simultaneous masking using notched-noise maskers, (2) two-tone suppression using forward maskers at the signal frequency (fs) and suppressor tones above fs, and (3) growth-of-masking functions in forward masking using a masking tone below fs. Signal frequencies of 750 and 3000 Hz were used to evaluate the effects of aspirin at relatively low- and high-frequency regions of the cochlea. In experiment 1, aspirin broadened the auditory filters and reduced the effect of level on frequency selectivity. In experiment 2, aspirin reduced or eliminated two-tone suppression. And, in experiment 3, aspirin reduced the slopes of the growth-of-masking functions. Thus, the aspirin was effective in reducing nonlinearity in all three experiments, suggesting that these measures reflect the same (or a similar) active, nonlinear mechanism, namely the compressive nonlinearity provided by the OHCs. In all experiments, aspirin tended to have larger detrimental effects on the nonlinear measures at 3000 Hz than at 750 Hz, which can be explained in terms of greater involvement of nonlinear processing at higher frequencies. Finally, these effects of aspirin were found to be similar to those observed in preliminary measurements in two subjects with mild, permanent hearing loss.

Adult↗

PubMed2003

Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery.

BACKGROUND: Aspirin inhibits platelet activation and reduces atherothrombotic complications in patients at risk of myocardial infarction and stroke. However, a sufficient inhibition of platelet function by aspirin is not always achieved. The causes of this aspirin resistance are unknown. METHODS AND RESULTS: Patients undergoing coronary artery bypass grafting (CABG) have a high incidence of aspirin resistance. To evaluate functional and biochemical responses to aspirin, platelet-rich plasma was obtained before and at days 1, 5, and 10 after CABG. Thromboxane formation, aggregation, and alpha-granule secretion were effectively inhibited by 30 or 100 micromol/L aspirin in vitro before CABG, but this inhibition was prevented or attenuated after CABG. Whereas the inhibition of thromboxane formation and aggregation by aspirin in vitro partly recovered at day 10 after CABG, oral aspirin (100 mg/d) remained ineffective. The inducible isoform of cyclooxygenase in platelets, COX-2, has been suggested to confer aspirin resistance. In fact, immunoreactive COX-2 was increased 16-fold in platelets at day 5 after CABG, but the COX-2 selective inhibitor celecoxib did not alter aspirin-resistant thromboxane formation. By contrast, the combined inhibitor of thromboxane synthase and thromboxane receptor antagonist terbogrel equally prevented thromboxane formation of platelets obtained before (control) and after CABG. CONCLUSIONS: Platelet aspirin resistance involves an impairment of both in vivo and in vitro inhibition of platelet functions and is probably due to a disturbed inhibition of platelet COX-1 by aspirin.

Arachidonic Acid↗

PubMed1980

Relative effects of aspirin on platelet aggregation and prostaglandin-mediated coronary vasodilatation in the dog.

Aspirin, as an inhibitor of platelet aggregation, may be of benefit in ischemic heart disease. However, aspirin blocks not only platelet aggregation but also synthesis of prostacyclin, a vasodilator and platelet deaggregator. The relative sensitivity of prostaglandin-mediated coronary vasodilatation and platelet aggregation to inhibition by aspirin remains uncertain. We therefore investigated the relative dose-response relationship of aspirin on arachidonic acid-induced increments in coronary blood flow and on ADP-induced aggregation of platelets. In 11 open-chest dogs, intracoronary arachidonic acid, 0.1-3.0 mg, produced dose-related increases in coronary blood flow that were inhibited progressively by i.v. aspirin over the dose range 0.3-3.0 mg/kg. Aspirin at 3 mg/kg almost completely obliterated the response to 3 mg of arachidonic acid. Similarly, aspirin doses of 0.3-3.0 mg/kg progressively raised the minimal concentration of ADP necessary for platelet aggregation. The threshold concentration of ADP that produced aggregation of platelets from 10 control dogs ranged from 2.3 x 10(-6) M to 1.2 x 10(-5) M. Aspirin at 3 mg/kg completely inhibited aggregation of platelets from 11 of 12 dogs, even with ADP at 2.3 x 10(-4) M concentration, the maximum tested. Aspirin at 0.1 mg/kg failed to inhibit either ADP-induced platelet aggregation or arachidonic acid-induced increments in coronary blood flow. Thus, the two test systems showed similar sensitivity to inhibition by aspirin with respect to threshold dose and maximal effect. These results show that very low doses of aspirin inhibit arachidonic acid-induced coronary vasodilatation and that aspirin at low doses does not appear to selectively inhibit platelet activity relative to coronary vasodilatation.

Adenosine Diphosphate↗

PubMed1995

Aspirin in the treatment of acute myocardial infarction in elderly Medicare beneficiaries. Patterns of use and outcomes.

BACKGROUND: Although aspirin is an effective, inexpensive, and safe treatment of acute myocardial infarction, the frequency of use of aspirin in actual medical practice is not known. Elderly patients, a group with low rates of utilization of effective therapies such as thrombolytic therapy, also may be at risk of not receiving aspirin for acute myocardial infarction. To address this issue, we sought to determine the current pattern of aspirin use and to assess its effectiveness in a large, population-based sample of elderly patients hospitalized with acute myocardial infarction. METHODS AND RESULTS: As part of the Cooperative Cardiovascular Project Pilot, a Health Care Financing Administration initiative to improve quality of care for Medicare beneficiaries, we abstracted hospital medical records of Medicare beneficiaries who were hospitalized in Alabama, Connecticut, Iowa, or Wisconsin from June 1992 through February 1993. Among the 10,018 patients > or = 65 years old who had no absolute contraindications to aspirin, 6140 patients (61%) received aspirin within the first 2 days of hospitalization. Patients who were older, had more comorbidity, presented without chest pain, and had high-risk characteristics such as heart failure and shock were less likely to receive aspirin. The use of aspirin was significantly associated with a lower mortality (OR, 0.78; 95% CI, 0.70 to 0.89) after adjustment for potential confounders. CONCLUSIONS: About one third of elderly patients with acute myocardial infarction who had no contraindications to aspirin therapy did not receive it within the first 2 days of hospitalization. The elderly patients with the highest risk of death were the least likely to receive aspirin. After adjustment for differences between the treatment groups, the use of aspirin was associated with 22% lower odds of 30-day mortality. The increased use of aspirin for patients with acute myocardial infarction is an excellent opportunity to improve the delivery of care to elderly patients.

Aged↗

PubMed1999

Administration time-dependent effects of aspirin in women at differing risk for preeclampsia.

This study extends previous results on the effects of low-dose aspirin on blood pressure in pregnant women at differing risk of developing hypertension in pregnancy and who received aspirin at different times according to their rest-activity cycle. A double-blind, randomized, placebo-controlled trial was conducted in 240 pregnant women randomly assigned to 1 of 6 groups according to treatment (placebo or aspirin, 100 mg/d, starting at 12 to 16 weeks of gestation) and the time of treatment: on awakening (time 1), 8 hours after awakening (time 2), or before bedtime (time 3). Blood pressure and heart rate for each subject were automatically monitored for 2 days every 4 weeks from the day of recruitment until delivery, as well as at puerperium (6 to 8 weeks after delivery). Subjects were further divided for comparative purposes according to the results of the tolerance-hyperbaric test for early identification of those with a higher risk for developing hypertensive complications in pregnancy. Results indicated that there was no effect of aspirin on blood pressure at time 1 (compared with placebo). A blood pressure reduction was, however, highly statistically significant at time 2 and, to a greater extent, at time 3 (mean reductions of 14.2 and 9.6 mm Hg in 24-hour means for systolic and diastolic blood pressure, respectively, at the time of delivery compared with placebo given at the same time). Effects of aspirin on blood pressure were significantly larger for women with a positive test at the time of recruitment (P<0.001). Differences in blood pressure among pregnant women receiving aspirin at different times in the circadian cycle disappeared at puerperium (P>0.212). There was no effect of aspirin or placebo on heart rate. This study corroborates the statistically significant, time-dependent effect of low-dose aspirin on blood pressure in pregnant women with differing risk of developing hypertensive complications in pregnancy. Although the mechanism involved in the administration-time-dependent responsiveness of blood pressure to aspirin still remains uncertain, the use of doses of aspirin <80 mg/d that do not affect placental thromboxane, initiation of the use of aspirin after 16 weeks' gestation, and the lack of circadian timing for aspirin administration could all explain the lack of positive results in previous clinical trials.

Administration, Oral↗

PubMed2006

Aspirin and decreased adult-onset asthma: randomized comparisons from the physicians' health study.

RATIONALE: In an observational cohort study, women who self-selected for frequent aspirin use developed less newly diagnosed asthma than women who did not take aspirin. OBJECTIVE: To explore whether low-dose aspirin decreased the risk of newly diagnosed asthma in a randomized, double-blind, placebo-controlled trial. METHODS: The Physicians' Health Study randomized 22,071 apparently healthy male physicians, aged 40-84 yr at baseline and tolerant of aspirin, over an 18-wk run-in period, to 325 mg aspirin or placebo on alternate days. The aspirin component was terminated after 4.9 yr due principally to the emergence of a statistically extreme 44% reduction in risk of first myocardial infarction among those randomly assigned to aspirin. MEASUREMENTS: Physicians could self-report an asthma diagnosis on questionnaires at baseline, 6 mo, and annually thereafter. Asthma was not an a priori endpoint of the trial. RESULTS: Among 22,040 physicians without reported asthma at randomization, there were 113 new asthma diagnoses in the aspirin group and 145 in the placebo group. The hazard ratio was 0.78 (95% confidence interval, 0.61-1.00; p = 0.045). This apparent 22% lower risk of newly diagnosed asthma among those assigned to aspirin was not modified by baseline characteristics including smoking, body mass index, or age. CONCLUSIONS: Aspirin reduced the risk of newly diagnosed adult-onset asthma in a large, randomized clinical trial of apparently healthy, aspirin-tolerant men. This result requires replication in randomized trials designed a priori to test this hypothesis; it does not imply that aspirin improves symptoms in patients with asthma.

Adult↗

PubMed1979

Recovery of endothelial cell prostacyclin production after inhibition by low doses of aspirin.

Endothelial cells synthesize prostacyclin (PGI(2)), an unstable prostaglandin that inhibits platelet aggregation and serotonin release. Because cyclooxygenase, which is necessary for synthesis of PGI(2), is inactivated by aspirin, we examined the effect of aspirin on PGI(2) production by cultured human endothelial cells. Endothelial cells synthesize PGI(2) (20.1+/-7.2 ng/10(6) cells, mean+/-SD) when stimulated with 20 muM sodium arachidonate for 2 min. PGI(2) production is inhibited by low-dose aspirin (5 muM); the t((1/2)) of inactivation is 6.0+/-1.3 min (mean+/-SEM, n = 3). Thus, endothelial cell cyclooxygenase is as sensitive to aspirin as the enzyme in platelets. After 1 h incubation with aspirin, endothelial cell PGI(2) production was inhibited 50% by 2.1+/-0.4 muM aspirin and was inhibited 90% by 6.2+/-0.9 muM aspirin (mean+/-SEM, n = 4). When endothelial cells were incubated with 100 muM aspirin, washed, and recultured, their ability to synthesize PGI(2) returned to control levels in 35.6+/-1.0 h (mean+/-SEM, n = 4). Recovery of endothelial PGI(2) production after aspirin depended on de novo protein synthesis because treatment with cycloheximide (3 mug/ml) inhibited recovery by 92%.These results indicate that although endothelial cell cyclooxygenase in vitro is inhibited by low concentrations of aspirin, endothelial cells rapidly resynthesize their cyclooxygenase after the aspirin is removed. This rapid resynthesis of cyclooxygenase lessens the likelihood that aspirin used in clinical doses promotes thrombosis.

Aspirin↗

PubMed2002

Comparison of high-dose and low-dose aspirin plus intravenous immunoglobulin in the treatment of Kawasaki syndrome.

The efficacy of intravenous immunoglobulin (IVIG) in the treatment of Kawasaki syndrome (KS) has been unequivocally established, but questions remain concerning the proper dose of adjunctive aspirin therapy in the treatment of KS. The medical records of 72 children with KS were reviewed. All patients were treated with IVIG; 21 received 400 mg/kg/dose on 4 consecutive days and 51 received 2 g/kg as a single infusion. Seventy patients also received aspirin. Twenty-four of the 70 patients were started on high-dose aspirin (80-100 mg/kg/day) at the time of diagnosis. High-dose aspirin was given for a mean (+/- SE) duration of 6.1+/-0.9 days, then switched to low-dose aspirin (3-5 mg/kg/day). Forty-six of the 70 patients were started on low-dose aspirin at the time of diagnosis and remained on low-dose aspirin for the duration of treatment. Coronary artery abnormalities were present at the time of diagnosis in 12 of 72 patients (17%), including 6 of 6 of patients (100%) with atypical KS and 6 of 66 patients (9%) with typical KS. None of the remaining 60 patients developed coronary artery abnormalities after treatment with IVIG and aspirin. The mean duration of fever after initiation of therapy was 44+/-6 hours in patients treated with IVIG 400 mg/kg/dose on 4 consecutive days and 35+/-5 hours in patients treated with 2 g/kg as a single infusion (p=0.3). The mean duration of fever after the initiation of therapy was 47+/-8 hours in patients treated with high-dose aspirin compared to 34+/-5 hours in patients treated with low-dose aspirin (p=0.13). These preliminary results indicate there is no benefit to high-dose aspirin compared to low-dose aspirin in the treatment of children with KS.

Aspirin↗

PubMed1997

The influence of dosage form on aspirin kinetics: implications for acute cardiovascular use.

In this study, the pharmacokinetics of several formulations of aspirin were examined: soluble aspirin, mouth-dispersible aspirin, plain aspirin and enteric-coated aspirin granules. Blood samples were taken at frequent intervals for 24 hours after single dosing in 12 healthy volunteers and Tmax, Cmax and t1/2 measured. Cmax was significantly higher for soluble aspirin than for the other formulations and the t1/2 was shorter. The results show the rapid absorption of aspirin from a soluble formulation compared with that from plain aspirin or enteric-coated aspirin granules. Recommendations to treat patients suspected of having a heart attack as soon as possible with aspirin are now widely accepted and the present study would suggest that soluble aspirin should be the aspirin of choice in this situation.

Adult↗