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PubMed2002

Cost effectiveness of aspirin, clopidogrel, or both for secondary prevention of coronary heart disease.

BACKGROUND: Both aspirin and clopidogrel reduce the rate of cardiovascular events in patients with coronary heart disease. We estimated the cost effectiveness of the increased use of aspirin, clopidogrel, or both for secondary prevention in patients with coronary heart disease. METHODS: We used the Coronary Heart Disease Policy Model, a computer simulation of the U.S. population, to estimate the incremental cost effectiveness (in dollars per quality-adjusted years of life gained) of four strategies in patients over 35 years of age with coronary disease from 2003 to 2027: aspirin for all eligible patients (i.e., those who were not allergic to or intolerant of aspirin), aspirin for all eligible patients plus clopidogrel for patients who were ineligible for aspirin, clopidogrel for all patients, and the combination of aspirin for all eligible patients plus clopidogrel for all patients. RESULTS: The extension of aspirin therapy from the current levels of use to all eligible patients for 25 years would have an estimated cost-effectiveness ratio of about $11,000 per quality-adjusted year of life gained. The addition of clopidogrel for the 5 percent of patients who are ineligible for aspirin would cost about $31,000 per quality-adjusted year of life gained. Clopidogrel alone in all patients or in routine combination with aspirin had an incremental cost of more than $130,000 per quality-adjusted year of life gained and remained financially unattractive across a wide range of assumptions. However, clopidogrel alone or in combination with aspirin would cost less than $50,000 per quality-adjusted year of life gained if its price were reduced by 70 to 82 percent, to $1.00 and $0.60 per day, respectively. CONCLUSIONS: Increased prescription of aspirin for secondary prevention of coronary heart disease is attractive from a cost-effectiveness perspective. Because clopidogrel is more costly, its incremental cost effectiveness is currently unattractive, unless its use is restricted to patients who are ineligible for aspirin.

Adult↗

PubMed2001

Prior aspirin users with acute non-ST-elevation coronary syndromes are at increased risk of cardiac events and benefit from enoxaparin.

BACKGROUND: The aim of this article was to investigate whether prior aspirin use in patients with acute coronary syndromes affects clinical outcome. The Efficacy Safety Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study (ESSENCE) and Thrombolysis in Myocardial Infarction (TIMI) 11B trials have shown superiority of enoxaparin over unfractionated heparin (UFH) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the treatment effect of enoxaparin in the subset of patients reporting prior aspirin use has not been determined. METHODS: The rate of death, myocardial infarction, and urgent revascularization at days 8 and 43 after randomization was compared among patients who received aspirin within the week before randomization with those who did not receive aspirin in the TIMI 11B trial. A total of 3275 patients (84%) were prior aspirin users. RESULTS: The admission diagnosis was similar for prior and nonprior aspirin users. At both day 8 and day 43 the event rate was higher for prior aspirin users than for nonprior aspirin users (odds ratio 1.6 [1.24-2.08], P =.0004 at day 43), even after correction for baseline characteristics. Compared with those prior aspirin users taking UFH, enoxaparin-treated prior aspirin users had a reduced rate of the composite end point of death, myocardial infarction, and urgent revascularization at day 8 (odds ratio 0.82 [0.67-1.00], P =.046) and day 43 (odds ratio 0.83 [0.70-0.98], P =.032). CONCLUSION: Patients with UA/NSTEMI and prior aspirin use had a 60% higher risk of death and cardiac ischemic events compared with nonprior aspirin users. On the basis of this subanalysis, enoxaparin is superior to UFH in all patients. In prior aspirin users the benefit is more clearly demonstrated.

Angina, Unstable↗

PubMed2006

Regular aspirin use and retinal microvascular signs: the Blue Mountains Eye Study.

OBJECTIVE: Hypertension is closely related to microvascular abnormalities and there is increasing interest in agents that target the microvasculature. The effect of aspirin on the microvasculature has not been well studied. We examined the cross-sectional and longitudinal associations between regular aspirin use and retinal microvascular signs. DESIGN AND METHODS: We digitized retinal photographs from participants of the Blue Mountains Eye Study cohort (1992-1994, n = 3654, aged over 49 years, and 1997-1999, n = 2335) and used a computer-assisted method to measure average retinal arteriolar and venular diameters. Information on the frequency of aspirin use was collected, with regular aspirin use defined as weekly or daily. RESULTS: Regular aspirin users comprised 21.2% (n = 775) of the baseline population. At baseline and in individuals who were on one or more antihypertensive medication, regular aspirin use was found to be associated with retinal arterioles on average 3.6 mum (95% confidence interval 1.0, 6.2) wider than those of non-users or occasional aspirin users, after adjusting for age, blood pressure, smoking, diabetes, non-steroidal anti-inflammatory drug use and other variables. Increasing frequency of aspirin use was associated with increasing retinal arteriolar diameter (Ptrend < 0.01). At 5-year follow-up, regular users of aspirin and antihypertensive medication(s) had wider retinal arterioles than those who used aspirin less regularly. Neither antihypertensive medication use alone nor aspirin use alone was associated with wider retinal vessels. CONCLUSION: Our finding of a possible association between the combined use of aspirin and antihypertensive agent(s) and wider retinal arteriolar diameter warrants further investigation into the effects of aspirin on the microvasculature.

Aged↗

PubMed1994

Effect of the 5-lipoxygenase inhibitor ZD2138 on aspirin-induced asthma.

BACKGROUND: The cysteinyl leukotrienes may play a central part in the mechanisms of aspirin-sensitive asthma. Previous work has shown that individuals with aspirin-sensitive asthma have high basal urinary LTE4 levels which increase further upon aspirin ingestion, and that sulphidopeptide leukotriene receptor antagonists attenuate aspirin-induced airflow obstruction. If the cysteinyl leukotrienes cause aspirin-induced asthmatic reactions, inhibition of the 5-lipoxygenase pathway should prevent aspirin-induced bronchospasm. This hypothesis has been tested with ZD2138, a specific non-redox 5-lipoxygenase inhibitor. METHODS: Seven subjects (four men) with aspirin-sensitive asthma with baseline FEV1 values > 67% were studied. ZD2138 (350 mg) or placebo was given on two separate occasions two weeks apart in a randomised double blind fashion. A single dose of aspirin was administered four hours after dosing and FEV1 was measured for six hours. Inhibition of the 5-lipoxygenase pathway by ZD2138 was assessed by measurements of urinary LTE4 levels and ex vivo calcium ionophore stimulated LTB4 generation in whole blood, before administration of drug or placebo and at regular time intervals after dosing and aspirin administration. RESULTS: ZD2138 protected against the aspirin-induced reduction in FEV1 with a 20.3 (4.9)% fall in FEV1 following placebo compared with 4.9 (2.9)% following ZD2138. This was associated with 72% inhibition of ex vivo LTB4 generation in whole blood at 12 hours and a 74% inhibition of the rise in urinary LTE4 excretion at six hours after aspirin ingestion. CONCLUSIONS: In aspirin-sensitive asthma the 5-lipoxygenase inhibitor ZD2138 inhibits the fall in FEV1 induced by aspirin and this is associated with substantial inhibition of 5-lipoxygenase.

Adult↗

PubMed1987

Does aspirin damage canine gastric mucosa by reducing its surface hydrophobicity?

Intraluminally administered aspirin disrupts the gastric mucosal barrier in a pH-dependent manner and may do so by compromising the hydrophobic or nonwettable lining to the stomach. We examined the pH dependence and time-course of aspirin's effects on barrier integrity by measuring the aspirin-induced changes in surface wettability, potential difference (PD), and electrical resistance (R) of canine gastric mucosa mounted in Ussing chambers. Luminal surface hydrophobicity, as determined by contact angle (CA) measurements, and PD were reduced by acidic aspirin solutions but were not reduced by acidic solutions without aspirin (pH 2.6) or by aspirin solutions that were neutral or only mildly acidic (pH greater than 4.0). Significant reductions in CA were correlated well with the proportion of aspirin in its lipid-soluble undissociated form (r = 0.93, P less than 0.001). Acidified-aspirin solutions significantly reduced CA and PD after a 2.5-min incubation period. Significant reductions in R occurred 25 min after exposure to acidified aspirin. Morphological damage to the gastric epithelium was not apparent after a 5-min exposure to acidified aspirin but was conspicuous 30 min after aspirin treatment. Aspirin-induced reductions in CA were highly associated with decreases in mucosal PD in both the pH and time-dependent studies (r = 0.93 and r = 0.99, respectively, P less than 0.001). These data support the hypothesis that the undissociated form of aspirin compromises the protective nonwettable lining of the stomach and in doing so, disrupts the gastric mucosal barrier.

Animals↗

PubMed1995

Adaptation of rat gastric mucosa to aspirin requires mucosal contact.

Adaptation of the gastric mucosa to repeated administration of aspirin is a well-documented phenomenon, but the underlying mechanism is not fully understood. In this study, we tested the hypothesis that adaptation of the rat stomach to chronic aspirin administration required contact between the aspirin and the gastric mucosa. Rats were orally treated twice daily with either aspirin (100 mg/kg) or the vehicle. After various periods of treatment (< or = 20 days), the rats were given a higher dose of aspirin (250 mg/kg po), and the extent of gastric damage was assessed 3 h later. Rats receiving chronic aspirin demonstrated the development, in a time-dependent manner, of resistance to the damaging effects of aspirin. Chronic aspirin administration also significantly decreased the susceptibility of the rat stomach to damage induced by indomethacin or naproxen. The adaptation phenomenon was associated with a parallel increase in inflammatory infiltration of the mucosa, as measured by tissue myeloperoxidase activity and histology. Prostaglandin synthesis was markedly suppressed (> 80%) in all rats treated with aspirin. Gastric mucosal ornithine decarboxylase activity was not affected by chronic aspirin administration. If aspirin was administered subcutaneously or intrajejunally for 20 days, neither adaptation nor inflammation of the gastric mucosa was observed. These studies demonstrate that the rat stomach adapts to chronic oral administration of aspirin, but not to aspirin administration via other routes. Adaptation of the gastric mucosa occurred in parallel to infiltration of granulocytes. Whether these two phenomena are mechanistically or causally linked is not yet clear.

Adaptation, Physiological↗

PubMed1985

Pharmacology of platelet inhibition in humans: implications of the salicylate-aspirin interaction.

The current dispute over the effects of "low" vs "high" doses of aspirin should take into consideration the pharmacokinetics of this drug. In fact, different pharmaceutical formulations of aspirin may deliver little or no aspirin to the systemic blood. This was the case, for instance, in healthy volunteers taking 320 mg of compressed aspirin or 800 mg of enteric-coated aspirin. In all instances thromboxane B2 generation in serum was fully inhibited. Platelet cyclooxygenase might therefore be effectively acetylated by exposure to aspirin in the portal circulation, whereas vascular cyclooxygenase could be spared. Thus aspirin formulations ensuring complete first-pass deacetylation should be sought rather than "low" or "high" doses of unspecified aspirin formulations. Regardless of the type and dose of aspirin administered, salicylate is formed and accumulates in the circulation. It may antagonize the effects of aspirin on cyclooxygenase, at least in acute conditions. As an example, after administration of 1 g of salicylate to healthy volunteers, when plasma levels of the drug were about 75 micrograms/ml, the effect of 40 mg iv aspirin (given 40 min later) on platelet cyclooxygenase and aggregation was significantly diminished. In contrast, in patients undergoing saphenectomy, the same dose of salicylate (1 g) gave plasma drug levels of about 25 micrograms/ml; salicylate was unable to prevent the inhibitory effect on platelets of 40 mg iv aspirin (given 1 hr later) but did act on vascular prostacyclin. Thus the combination of salicylate with aspirin at an appropriate dose and blood level ratio may result in almost complete dissociation of the drug's effect on platelets and vessels in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Results of the APRICOT Study.

BACKGROUND: Successful coronary thrombolysis involves a risk for reocclusion that cannot be prevented by invasive strategies. Therefore, we studied the effects of three antithrombotic regimens on the angiographic and clinical courses after successful thrombolysis. METHODS AND RESULTS: Patients treated with intravenous thrombolytic therapy followed by intravenous heparin were eligible when a patent infarct-related artery was demonstrated at angiography < 48 hours. Three hundred patients were randomized to either 325 mg aspirin daily or placebo with discontinuation of heparin or to Coumadin with continuation of heparin until oral anticoagulation was established (international normalized ratio, 2.8-4.0). After 3 months, in which conservative treatment was intended, vessel patency and ventricular function were reassessed in 248 patients. Reocclusion rates were not significantly different: 25% (23 of 93) with aspirin, 30% (24 of 81) with Coumadin, and 32% (24 of 74) with placebo. Reinfarction was seen in 3% of patients on aspirin, in 8% on Coumadin, and in 11% on placebo (aspirin versus placebo, p < 0.025; other comparison, p = NS). Revascularization rate was 6% with aspirin, 13% with Coumadin, and 16% with placebo (aspirin versus placebo, p < 0.05; other comparisons, p = NS). Mortality was 2% and did not differ between groups. An event-free clinical course was seen in 93% with aspirin, in 82% with Coumadin, and in 76% with placebo (aspirin versus placebo, p < 0.001; aspirin versus Coumadin, p < 0.05). An event-free course without reocclusion was observed in 73% with aspirin, in 63% with Coumadin, and in 59% with placebo (p = NS). An increase of left ventricular ejection fraction was only found in the aspirin group (4.6%, p < 0.001). CONCLUSIONS: At 3 months after successful thrombolysis, reocclusion occurred in about 30% of patients, regardless of the use of antithrombotics. Compared with placebo, aspirin significantly reduces reinfarction rate and revascularization rate, improves event-free survival, and better preserves left ventricular function. The efficacy of Coumadin on these end points appears less than that of aspirin. The still-high reocclusion rate emphasizes the need for better antithrombotic therapy in these patients.

Aged↗

PubMed1989

Combination therapy with low-dose aspirin and ticlopidine in cerebral ischemia.

We compared combination therapy with low-dose aspirin plus ticlopidine to therapy with aspirin alone or ticlopidine alone in patients suffering transient ischemic attack or cerebral infarction. In 17, 24, and 23 patients, respectively, 300 mg/day aspirin, 200 mg/day ticlopidine, and 81 mg/day aspirin plus 100 mg/day ticlopidine were administered orally. Aspirin alone markedly inhibited platelet aggregation induced by arachidonic acid, partially inhibited platelet aggregation induced by adenosine diphosphate, and did not inhibit platelet aggregation induced by platelet activating factor. Ticlopidine alone inhibited platelet aggregation induced by adenosine diphosphate and platelet activating factor, but did not inhibit platelet aggregation induced by arachidonic acid. Combination therapy with aspirin plus ticlopidine markedly inhibited platelet aggregation induced by all three agonists. Plasma concentrations of beta-thromboglobulin and platelet factor 4 remained unchanged by aspirin alone, were slightly reduced by ticlopidine alone, and were markedly reduced by aspirin plus ticlopidine. Plasma concentration of thromboxane B2 was reduced by aspirin alone or with ticlopidine, but not by ticlopidine alone. The level of 6-ketoprostaglandin F1 alpha was reduced only by aspirin alone. Bleeding time was significantly prolonged by aspirin alone and by ticlopidine alone, although the greatest prolongation was produced by aspirin plus ticlopidine. Our results indicate that the combination of aspirin plus ticlopidine is a potent antiplatelet strategy, although the clinical importance of the changes observed need to be determined by a properly designed and controlled prospective study.

6-Ketoprostaglandin F1 alpha↗

PubMed1976

Effect of aspirin on normal and cholera toxin-stimulated intestinal electrolyte transport.

The effect of aspirin on normal and cholera toxin-stimulated electrolyte transport has been investigated in vitro, because this drug appears to inhibit cholera toxin-induced intestinal secretion in in vivo animal models. In the Ussing chamber, 10 mM aspirin decreased the control rabbit ileal potential difference and short-circuit current by 50% and increased conductance by 28%. Bidirectional electrolyte flux determinations showed that aspirin significantly increased both Na and Cl absorption and reduced flux (which probably represents HCO3 secretion) to zero. This effect of aspirin appears to be identical to that reported to others with catecholamines as determined with similar techniques. However, alpha-adrenergic blockers did not prevent the electrical effects of aspirin, suggesting that aspirin does not have its effect through release of tissue stores of catecholamines. In the presence of aspirin, cholera toxin increased the potential difference and short-circuit current, and decreased the conductance of rabbit ileum in a fashion qualitatively similar to control tissues. However, aspirin reversed cholera toxin-stimulated Na transport from secretion to absorption, inhibited cholera toxin, induced Cl secretion by 58% and partially, but not significantly, inhibited HCO3 secretion. Thus, the inhibitory effect of aspirin on cholera toxin-induced electrolyte secretion appears to be due to aspirin-stimulated Na and Cl absorption. Although aspirin reduced tissue cyclic AMP concentrations in normal and cholera toxin-stimulated ileum, it also inhibited the electrolyte secretion induced by exogenous cyclic AMP. Thus, if aspirin's stimulatory effect on sodium and anion absorption in normal tissue and its inhibitory effect on cholera toxin-stimulated sodium and anion secretion involves a cyclic AMP-mediated system, the effect must be a step distal to cyclic AMP production or degradation. The exact mechanism of aspirin's effect on normal and cholera toxin-induced electrolyte transport, and its possible usefulness in the treatment of cholera diarrhea, remains to be determined.

Animals↗

PubMed2005

High frequency of aspirin resistance in patients with acute coronary syndrome.

Aspirin is widely used for secondary prevention of cardiovascular disease, but is not effective for all patients. This phenomenon is called as aspirin resistance. Although the prognosis is worse in patients who develop acute coronary syndrome (ACS) while using aspirin, the frequency of aspirin resistance in these patients has not been evaluated. We aimed to evaluate the frequency of aspirin resistance in patients with ACS and to determine its relationship with the angiographic severity and extent of the associated coronary artery disease. The present study included 104 patients with ACS (75 men, 60.4 +/- 10.8 years) who were hospitalized while using aspirin for at least last 7 days and 100 patients with stable coronary artery disease (73 men, 57.6 +/- 10.6 years), documented by coronary angiography, history of revascularization or myocardial infarction (MI), and the use of aspirin for last 7 days. The latter group had no MI or ACS for last 3 months. Platelet function was assessed with PFA-100, which simulates primary homeostasis at injured blood vessels. Coronary angiography was performed in 83 cases of the patients with ACS during hospital stay. Aspirin resistance is more prevalent in patients with ACS (40.3%) when compared with stable coronary artery disease patients (27%). The difference was statistically significant (p = 0.04). The ACS patients with aspirin resistance were older and had severe myocardial damage. However, there were no significant differences in angiographic severity and extent of coronary artery disease between aspirin-resistant and aspirin-sensitive patients. Frequency of aspirin resistance is higher in patients who develop ACS while using aspirin than that in patients with stable coronary artery disease.

Adult↗

PubMed2003

Decisional attributes of patients with diabetes: the aspirin choice.

OBJECTIVE: The aim of this study was to determine personal characteristics and preferences that affect decision making (decisional attributes) in patients with diabetes. In particular, we were interested in relating these attributes to the choice of using aspirin to reduce cardiovascular risk. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional survey (70% response rate) of 206 diabetic patients (median age, 63 years; 42% women; 91% completed high school; median HbA(1c), 8%) attending a tertiary care diabetes clinic. Patients answered a 42-question survey exploring decisional attributes. Medical records provided the source of clinical information. We evaluated sociodemographic, clinical, and decisional predictors of aspirin use. We also conducted a multivariable analysis with aspirin use as a dependent variable. RESULTS: Sixty-seven percent of patients surveyed used aspirin. Patients using aspirin were at higher risk of cardiovascular disease (odds ratio 1.4, 95% CI 1.0-2.1), knew more about the benefits of aspirin (1.9, 1.4-2.6) and less about the risks of aspirin (1.4, 1.2-1.8), and were more certain about using aspirin (0.5, 0.3-0.8) than patients not using aspirin. Patients using aspirin placed a higher value on preventing cardiovascular events than on avoiding the side effects of aspirin. Patients perceived that their diabetes provider and the American Diabetes Association had greater influence on their decision to use aspirin than family members or other patients with diabetes. CONCLUSIONS: The decisional attributes of patients with diabetes are associated with aspirin use. Decisional attributes may be the target of research and interventions to reduce underutilization to levels consistent with patient preferences.

Adult↗

PubMedDate not supplied

Effect of aspirin on hemostasis and thrombosis.

Aspirin inhibits platelet function by acetylating platelet cyclo-oxygenase. When aspirin is administered in doses as low as 40-160 mg per day, it inhibits platelet cyclo-oxygenase activity by more than 80%. The effect of aspirin on platelet function is maintained for the life-span of the platelet and there is evidence that aspirin also acetylates platelets before they are released in the circulation and while they are still within megakaryocytes. Aspirin also inhibits the synthesis of PGI2 by vascular wall cells but compared to the platelet, this vessel wall effect is relatively short-lived and requires slightly larger doses of aspirin. In vivo studies in rabbits indicate that very high doses of aspirin are thrombogenic. However, there is no evidence that aspirin is thrombogenic in man even when administered in high therapeutic doses. The optimal antithrombotic dose of aspirin has not yet been determined. Clinically, impressive results have been obtained with low doses of aspirin (ranging from 100 to 300 mg per day) in preventing aorta coronary bypass thrombosis, in patients undergoing hemodialysis, and in patients with unstable angina. Aspirin is also effective in preventing stroke and death in patients with cerebral ischemia when administered in doses of approximately 1 gram per day. There are trends suggesting that aspirin is effective when administered in doses between 300 mg per day and 1500 mg per day in patients who have survived myocardial infarction. The side-effects of aspirin are mainly gastrointestinal and are dose-related. Generalized bleeding is very uncommon and limited mainly to patients with other hemostatic abnormalities or due to the concomitant use of anticoagulant therapy.

Animals↗

PubMed2000

Effect of sodium arachidonate on thrombin generation through platelet activation--inhibitory effect of aspirin.

BACKGROUND: Sodium arachidonate was used in this study to determine its capacity to generate thrombin through platelet activation. Whether aspirin prevent this effect was also investigated. METHODS AND RESULTS: Seventeen healthy volunteers without and after 160 mg/day aspirin intake for 3-5 days were studied. Lag-time and TG at basal condition and after platelet stimulation by sodium arachidonate (AA) were measured in normal non-aspirinated as well as "in vivo" aspirinated platelet rich plasma. (PRP). The lag-time was statistically significant shorter in non-aspirinated PRP activated with AA compared with non-activated PRP. This effect was inhibited by aspirin. In non-aspirinated PRP, there was an increase of TG at 4 and 6 min. incubation when platelets were activated with AA but the difference disappeared after 8 min. incubation, (84 +/- 71; 148 +/- 58 and 142 +/- 92 nmol/L respectively) compared with non-aspirinated. non-activated platelets (16 +/- 23; 55 +/- 56 and 111 +/- 76 nmol/L at 4,6 and 8 min, p < 0.0001, p < 0.0001 and p = 0.292, respectively). The AUCo-->22 min were 520.6 +/- 545.5 in non-aspirinated, non-stimulated PRP and 808.9 +/- 617, in non-aspirinated PRP activated with sodium arachidonate (p = 0.014). Aspirin administered in vivo produced a decrease of TG in PRP activated with AA. CONCLUSION: Platelet activated by AA trigged TG. This effect was inhibited by aspirin and could be an additional beneficial effect of aspirin in the prevention of thrombosis.

Adult↗

PubMed1992

[Effect of intravenous injection of aspirin on the cochlea].

It is not yet well understood how aspirin acts on the auditory system. This study was aimed at elucidating the effects of aspirin on the cochlear hair cells and cochlear nerve of guinea pigs by recording (1) spontaneous activity of cochlear nerve fibers, (2) compound action potentials (CAPs) evoked by electrical pulses applied to the cochlea through the round window membrane, (3) acoustically evoked action potentials (APs) through the round window membrane and (4) acoustic emissions (sound pressure near the tympanic membrane) evoked by electrical pulses applied to the cochlea. The following results were obtained. (1) After guinea pigs were given aspirin (200 mg/kg) intravenously, a transient reduction in spontaneous activity of cochlear nerve fibers and elevation over the subsequent 10-20 minutes were observed in three of four fibers recorded for more than 30 minutes. The mean spontaneous discharge rate in 102 fibers after aspirin administration (200 mg/kg) was not significantly higher than the control values from 30 to 120 minutes after aspirin administration, while the rate in 112 fibers after aspirin administration (400 mg/kg) was significantly higher. (2) After injecting of 100 mg/kg, 200 mg/kg and 400 mg/kg of aspirin, the amplitude of electrically evoked CAPs decreased significantly, while their latency increased significantly only after injection of 400 mg/kg of aspirin. (3) Changes in the amplitude of acoustically evoked APs and electrically evoked CAPs were compared before and after intravenous injections of 400 mg/kg of aspirin. The AP suppression ratio at low sound intensity was significantly greater than that of CAPs at low and high current levels. (4) After injection of 400 mg/kg of aspirin, the waves of electrically evoked acoustic emissions and their peaks in the frequency analysis disappeared either reversibly or irreversibly. The observed changes in spontaneous activity of cochlear nerve fibers in response to aspirin administration to guinea pigs may represent a tinnitus-like phenomenon. The detection of electrically evoked CAPs suggests that aspirin acts on the cochlear nerve and causes a decrease in its excitability, and the discovery of acoustically evoked APs and electrically evoked acoustic emissions is interpreted as indicating that aspirin acts not only on the cochlear nerve but also on cochlear hair cells.

Acoustic Stimulation↗

PubMed2006

Effect of aspirin plus clopidogrel on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study was to determine whether aspirin plus clopidogrel can further suppress inflammation in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS: One hundred and fifteen patients with NSTEACS were randomized into two groups: group A (aspirin alone, n =58) and group B (aspirin plus clopidogrel, n =57). Patients in group A received a loading dose of 300 mg aspirin, then 100 mg per day. The patients in group B received a loading dose of 300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel per day. Serum high sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha) were measured in all patients at baseline prior to any drug treatment after admission, and at 7 and 30 days after beginning drug treatment. Thirty healthy volunteers on no medications were enrolled as controls (group C). RESULTS: Baseline levels of hs-CRP and TNF-alpha in group A and group B were significantly higher than those in group C. Seven days after administration, the levels of hs-CRP in both group A and group B decreased significantly [Group A: (6.15 +/- 1.39) mg/L vs (9.18 +/- 1.62) mg/L, P <0.01; Group B:(4.99 +/- 1.62) mg/L vs (10.29 +/- 1.47) mg/L, P <0.01]. Similarly, levels of TNF- alpha in both groups decreased at 7 days compared to baseline [Group A: (90.99 +/- 28.91) pg/ml vs (117.20 +/- 37.13) pg/ml, P <0.01; Group B: (74.32 +/- 21.83) pg/ml vs (115.27 +/- 32.11) pg/ml, P <0.01]. Thirty days after administration, the levels of hs-CRP in both group A and group B decreased further to (3.49 +/- 1.53) mg/L, and (2.40 +/- 1.17) mg/L respectively (P <0.01 for both comparisons). Levels of TNF-alpha in groups A and B also decreased significantly between 7 and 30 days, to 63.28 +/- 29.01 pg/ml (group A) and (43.95 +/- 17.10) pg/ml (group B; P <0.01 for both comparisons). Significantly lower levels of hs-CRP and TNF-alpha were observed in group B compared to Group A at thirty days after initiating drug treatment (P <0.05). CONCLUSIONS: Aspirin plus clopidogrel treatment reduced levels of serum hs-CRP and TNF-alpha in patients with NSTEACS significantly more than aspirin alone. Because both aspirin and clopidogrel produce important anti-inflammatory effects, these results suggest the possibility that long-term treatment with aspirin plus clopidogrel may produce greater clinical benefits compared to treatment with aspirin alone.

Adult↗

PubMedDate not supplied

Profile and prevalence of aspirin resistance in Indian patients with coronary artery disease.

BACKGROUND: Aspirin resistance is considered to be an enigma and the data available on aspirin resistance is scarce. This study was initiated to prospectively evaluate the prevalence of aspirin resistance in patients with stable coronary artery disease by using an established method of optical platelet aggregation. METHODS AND RESULTS: We studied 50 patients who were on 150 mg of aspirin for the previous 7 days. Fasting blood samples were assessed using optical platelet aggregation (Chronolog Corp, USA). The mean platelet aggregation with 10 microm of adenosine diphosphate in our patient group was 49.42 +/- 23.29% and with 0.5 mg/ ml of arachidonic acid it was 13.58 +/- 21.40%. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microm of adenosine diphosphate and a mean aggregation of > or =20% with 0.5 mg/ml of arachidonic acid. Aspirin semi responders were defined as those meeting only one of the criteria. Based on these criteria, 2.08% patients were found to be aspirin-resistant, 39.58% were aspirin semi responders and 58.33% were aspirin responders. Females tended to be more aspirin semi responsive (p = 0.08). All other parameters tested, namely, age, smoking, diabetes mellitus, hypertension, obesity, lipids, hemoglobin, platelet count, ejection fraction and drug intake did not show any statistically significant difference among the groups. Thus, in our group 41.66% patients showed inadequate response to aspirin. CONCLUSIONS: This study shows that aspirin resistance and aspirin semi responsiveness do occur in the Indian patients and there are no reliable clinical predictors for this condition. The diagnosis therefore relies primarily on laboratory tests.

Adult↗

PubMed1991

Presystemic acetylation of platelets by aspirin: reduction in rate of drug delivery to improve biochemical selectivity for thromboxane A2.

The utility of aspirin in the treatment of vascular occlusive disease has been ascribed to its blockade of platelet thromboxane A2 (TxA2), a potent inhibitor of vascular smooth muscle contraction and platelet aggregation. Coincident with the inhibition of TxA2 by aspirin at currently used dose regimens is a decrease in formation of prostacyclin (PGI2), an eicosanoid with opposing effects to TxA2 in vivo. The coincident inhibition of PGI2 could potentially limit the therapeutic efficacy of aspirin. This study addressed the issue as to whether a reduction in the rate of drug delivery could enhance the biochemical selectivity of aspirin toward inhibition of TxA2. Intubation studies were performed in parallel groups of healthy volunteers in which a 50-mg aspirin dose was administered as either a bolus or a 5 or 10 mg/hr infusion via a nasogastric tube. A control group received buffer solution. Systemic plasma levels of aspirin, major urinary metabolites of TxA2 and PGI2 and serum thromboxane B2 levels ex vivo were evaluated. Relative to the group receiving bolus aspirin, the slower rates of aspirin delivery increased the effective selectivity of the administered aspirin for TxA2. To investigate further this apparent selectivity, controlled release (CR) dose forms of aspirin were prepared and evaluated in a preliminary dose-ranging study in healthy subjects. The doses studied were 50 and 75 mg CR and a 75-mg aspirin solution. The CR aspirin dose forms decreased the maximal plasma concentration of aspirin relative to a bolus dose. The pharmacodynamic effects of the CR formulations were assessed via measurement of ex vivo serum thromboxane B2 formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗