Antiplatelet Effect Of Aspirin Research Articles

Ibuprofen: pharmacology, efficacy and safety

This review attempts to bring together information from a large number of recent studies on the clinical uses, safety and pharmacological properties of ibuprofen. Ibuprofen is widely used in many countries for the relief of symptoms of pain, inflammation and fever. The evidence for modes of action of ibuprofen are considered in relation to its actions in controlling inflammation, pain and fever, as well as the adverse effects of the drug. At low doses (800-1,200 mg day(-1)) which in many countries are approved for non-prescription (over-the-counter) sale ibuprofen has a good safety profile comparable with paracetamol. Its analgesic activity is linked to its anti-inflammatory effects and is related to reduction in the ex vivo production in blood of cyclo-oxygenase (COX)-1 and COX-2 derived prostanoids. Higher prescription doses (circa 1,800-2,400 mg day(-1)) are employed long-term for the treatment of rheumatic and other more severe musculo-skeletal conditions. Recent evidence from large-scale clinical trials with the newer coxibs, where ibuprofen was as a comparator, have confirmed earlier studies which have shown that ibuprofen has comparable therapeutic benefits with coxibs and other NSAIDs. For long-term usage (6+ months) there are greater numbers of drop-outs due to reduced effectiveness of therapy, a feature which is common with NSAIDs. Spontaneous reports of adverse events and adverse drug reactions (ADRs) in clinical trails from long-term coxib comparator studies, as well as in epidemiological studies, shows that ibuprofen has relatively low risks for gastro-intestinal (GI), hepato-renal and other, rarer, ADRs compared with other NSAIDs and coxibs. A slightly higher risk of cardiovascular (CV) events has been reported in some, but not all studies, but the risks are in general lower than with some coxibs and diclofenac. The possibility that ibuprofen may interfere with the anti-platelet effects of aspirin, though arguably of low grade or significance, has given rise to caution on its use in patients that are at risk for CV conditions that take aspirin for preventing these conditions. Paediatric use of ibuprofen is reviewed and the main results are that the drug is relatively safe and effective as a treatment of acute pain and fever. It is probably more effective than paracetamol as an antipyretic. This assessment of the safety and benefits of ibuprofen can be summarized thus: (1) Ibuprofen at OTC doses has low possibilities of serious GI events, and little prospect of developing renal and associated CV events. Ibuprofen OTC does not represent a risk for developing liver injury especially the irreversible liver damage observed with paracetamol and the occasional liver reactions from aspirin. (2) The pharmacokinetic properties of ibuprofen, especially the short plasma half-life of elimination, lack of development of pathologically related metabolites (e.g. covalent modification of liver proteins by the quinine-imine metabolite of paracetamol or irreversible acetylation of biomolecules by aspirin) are support for the view that these pharmacokinetic and notably metabolic effects of ibuprofen favour its low toxic potential. (3) The multiple actions of ibuprofen in controlling inflammation combine with moderate inhibition of COX-1 and COX-2 and low residence time of the drug in the body may account for the low GI, CV and renal risks from ibuprofen, especially at OTC doses.

The antiplatelet effect of aspirin is reduced by proton pump inhibitors in patients with coronary artery disease

ObjectiveTo evaluate the effect of proton pump inhibitors (PPIs) on the platelet response to aspirin in patients with coronary artery disease (CAD).DesignCase–control study.Patients418 stable patients with CAD, 54 of whom...

Aspirin Resistance in Healthy Drug-Naive Men Versus Women (from the Heredity and Phenotype Intervention Heart Study)

This study was designed to determine the factors that contribute to interindividual variation in the antiplatelet effects of aspirin. We measured platelet response to aspirin in 745 (400 men and 345 women) drug-naive asymptomatic subjects of the Heredity and Phenotype Intervention (HAPI) Heart Study. Whole blood platelet aggregometry was performed to assess response to arachidonic acid, adenosine diphosphate, and collagen at baseline and after 14 days of aspirin 81 mg/day. There was wide interindividual variation in platelet aggregation in response to aspirin, with no clear biological threshold to define aspirin resistance. Variation in platelet function before and after aspirin was heritable. Women exhibited greater platelet aggregability in response to adenosine diphosphate and collagen at baseline and after aspirin administration. The degree to which aspirin inhibited collagen-induced platelet aggregation was also significantly less in women compared with men (mean +/- SD percent inhibition of collagen-induced [1 microg/ml] platelet aggregation 49.9 +/- 30.9 vs 57.5 +/- 42.5 in women and men, respectively, p = 0.005). Using a cutoff <70% inhibition of collagen-induced platelet aggregation, 21% of the total population demonstrated aspirin resistance, which occurred in 30% of women and 16% of men (p = 0.0002). Aspirin-resistant subjects were older, had significantly higher total cholesterol and low-density lipoprotein cholesterol levels, lower hematocrit, and higher platelet count compared with aspirin-sensitive subjects. In conclusion, in this study group, platelet function is heritable. There is wide interindividual variation in platelet response to aspirin as defined by whole blood platelet aggregometry, with women having lower mean percent inhibition of platelet aggregation and greater prevalence of aspirin resistance than men.

Antiplatelet effects of aspirin with phytosterols: Comparison with non-enteric coated aspirin alone

The novel combination of aspirin and phytosterols may be a potential strategy to treat patients with cardiovascular disease. We sought to determine if the antiplatelet effects of a combination caplet of 81 mg aspirin with 400 mg phytosterols differed from the antiplatelet effects of non-enteric coated aspirin. The first five days of aspirin therapy alone (T1) produced marked reductions in collagen-induced, ADP-induced, and archidonic acid- induced platelet aggregation, and in serum and urine TxB 2 compared to baseline. Five days after randomization to aspirin alone versus aspirin + phytosterols (T2), there were no differences in any measurement of platelet function within each group compared to T1 or between groups. The present study suggests that the antiplatelet effect of non-enteric coated 81 mg twice-daily aspirin therapy alone is not affected by the addition of phytosterols in a combination product.

CardioPulse: sensing the cardiovascular world

![Graphic][1] Scientific journals attempt to publish the best original research and the most comprehensive review articles in their field—and, indeed, this is the very reason for their existence. However, data and their interpretation and guidelines and their implementation are not the complete picture: behind every article, there is a young Fellow and an established investigator with their own views and environment they work in. Behind every guideline, there is a committee that tried to consider all aspects and all differences in clinical practice of various healthcare systems. Behind every university, there are politics as well as cultural values, and an economic system that determines many aspects of their life. CardioPulse tries to look behind the scenes, talks to the persons behind a discovery, discovers cardiovascular medicine in developing countries, and visits leading institutes around the world. Throughout history and until the Second World War, infections and tuberculosis, in particular, were the main problems clinicians faced, but soon thereafter, cardiovascular diseases became the major epidemic in the Western world. Since then, cardiovascular medicine has grown into a large and expanding field, boosted by the highly publicized myocardial infarction of the president of the United States, Dwight D. Eisenhower on 23 September 1955. With the campaigns against smoking, the implementation of defibrillators by Bernard Lawn in the 1960s, the introduction of coronary care units by Desmond Julian and others, the discovery of the anti-platelet effects of aspirin by Sir John Vane, the development of Beta-blockers by Sir Henry Black, the first bypass operation by Rene Favoloro in 1967 and later the use of thrombolysis, ACE-inhibitors, Statins and finally, the invention of percutaneous interventions with a balloon catheter by Andreas Gruntzig in 1977, heart disease has become a treatable condition, and later, even preventable. As a consequence, its prevalence and incidence and its mortality, … [1]: /embed/inline-graphic-1.gif

Variabilité de réponse plaquettaire à l’aspirine et nouvelles cibles thérapeutiques

Aspirin is the first-line oral antiplatelet drug to prevent thromboembolic arterial occlusions. Aspirin irreversibly inhibits cyclooxygenase (COX) 1 involved in the platelet production of thromboxane (TX) A(2), an inducer of vasoconstriction and a platelet activating agent. Recurrent vascular events despite aspirin intake, combined with laboratory evidence of poor antiplatelet effect, suggested what has been called "aspirin resistance". For clarity's sake a real aspirin resistance would be the absence of COX1 inhibition due to intrinsic platelet factors (which has never been reported). What has been described is (expected) variability. COX1 inhibition can be insufficient to modify TX-dependent platelet behaviour. Other agonists, the production of which does not involve COX1, can stimulate TX-receptors. The antiplatelet effect of aspirin can be insufficient for pharmacokinetic or pharmacodynamic reasons, the latter being further classified as TX-dependent or not. If platelets are so reactive that responses are more TX-independent than normally, then neither aspirin nor any drugs acting on this pathway can do the job. These mechanisms should be better understood and diagnosed, and this is the prerequisite for the development of newer antiplatelet agents.

Abstract 3730: Celecoxib Does Not Deteriorate Antiplatelet Effects of Aspirin and Clopidogrel in Healthy Volunteers

Background: Celecoxib, cyclooxygenase (COX)-2 inhibitor, has been reported to inhibit neointimal hyperplasia in animal studies and to reduce restenosis after coronary stenting in COREA-TAXUS clinical trial. The main concern is that celecoxib would increase thrombogenecity by inhibiting the synthesis of prostacyclin in endothelial cells. However, it is not known whether the administration of celecoxib would weaken antiplatelet effects of aspirin and clopidogrel which are used after stenting. Methods: We recruited healthy volunteers (n=40) and randomized them into five subgroups. Each subject received the medication for 6 days and blood samples were taken day 0 and 7. Celecoxib 200mg twice a day, and/or aspirin 100mg daily, and/or clopidogrel 75 mg daily was administered. We compared platelet function by using light transmittance aggregometry and arachidonic acid metabolite assay among subgroups. Results: Celecoxib single treatment did not significantly affect platelet aggregation. Dual asprin and Plavix treatment inhibited platelet aggregation by 53%, which was not affected by addition of celecoxib showing 52% inhibition (t-test: p = 0.873). The changes of prostacyclin level did not differ among each treatment group (ANOVA: p=0.193). Although statistically not significant, celecoxib seems to lower the thromboxane level further when added to antiplatelet agents. Conclusion: Celecoxib treatment did not interfere with antiplatelet effect of aspirin or clopidogrel, suggesting that celecoxib as anti-restenosis agent would be administered safely during coverage of dual antiplatelet therapy in patients with coronary stenting without increasing thrombogenecity.

Aspirin is insufficient in inhibition of platelet aggregation and thromboxane formation early after coronary artery bypass surgery

Aspirin administered early after coronary artery bypass grafting surgery (CABG) improves graft patency and patients survival. However, the antiplatelet effect of aspirin seems to be variable and aspirin resistance is currently still being discussed. The aim of the study was to assess aspirin efficacy in the early postoperative period. Forty patients undergoing elective CABG surgery (20 in on-pump and 20 in off-pump) were enrolled in the study. Functional and biochemical responses to aspirin were evaluated by arachidonic acid (ARA)-induced platelet aggregation and urine 11-dehydro Thromboxane B2 metabolite excretion. Samples were collected before surgery (baseline; > or =7 days after aspirin withdrawal) and on days 1, 2 and 5 after surgery. Median baseline ARA aggregability was 55%. On day 1, platelet aggregability decreased (12%, P < 0.001). On day 2, despite the aspirin administration, platelet aggregability exceeded the values from day 1 (38%, P < 0.001). Only on day 5, sufficient inhibition of platelet aggregation was achieved (8%, P < 0.001). Median preoperative urine concentration of 11-dehydroTxB2 was 106 ng/mmol of creatinine. On day 1, the concentration decreased only slightly and insignificantly (97 ng/ml, P = NS), similarly as on day 2 (86 ng/ml, P = NS). Only on day 5, significant decrease in concentration of thromboxane metabolite was achieved compared to preoperative values (46 ng/ml, P = 0.001). Aspirin did not sufficiently inhibit platelet aggregation and thromboxane formation in the early postoperative period. Thus, antiplatelet treatment strategy should be intensified or modified in patients early after bypass surgery.

Monitoring aspirin treatment in patients with thrombocytosis: Comparison of the platelet function analyzer (PFA)-100 with optical aggregometry

Aspirin provides satisfactory protection against thrombotic episodes in essential thrombocythemia (ET), but at higher platelet counts has been less effective. Our aim was to compare the platelet function analyzer (PFA)-100 with optical aggregometry in order to determine a reliable method in monitoring aspirin's influence on platelet function in patients with thrombocytosis. We studied 36 patients with thrombocytosis. Sixteen of them, receiving aspirin, composed group A, while group B consisted of 20 patients not taking aspirin. In all patients, we compared the platelet function measured by classic optical aggregation tests with closure times (CT) obtained by the PFA-100. The definition of platelet responses as normal or pathological showed that PFA-100 collagen and/or epinephrine (CEPI) CTs and epinephrine-induced aggregometry is the pair of methods with the higher agreement in monitoring of platelet dysfunction due to ASA treatment (a = 94%). Satisfactory results were also obtained for group B (a = 81%). The comparison between PFA-100 CEPI CTs and arachidonic acid-induced aggregometry exhibited moderate agreement both in the total number of patients and in group A (a = 79% and 94%, respectively). PFA-100 collagen and/or ADP (CADP) CTs and ADP-induced aggregometry were not concordant. The PFA-100 system appears to be a reliable and rapid method in the assessment of aspirin's antiplatelet effect in patients with thrombocytosis. Regarding aggregometry, the selection of the inducer, its concentration and cut-off points is crucial in defining the response to antiaggregating agents. It still remains to determine whether there is any relevance between the measurements obtained by these methods and clinical outcome in thrombocythemic patients.

Action of Aspirin on Whole Blood-Aggregation Evaluated by the Screen Filtration Pressure Method

There are few monitoring systems widely used in clinical practice for evaluating the effectiveness of aspirin therapy, so in the present study aspirin's antiplatelet effects we investigated with a whole blood aggregometer using a screen filtration pressure (SFP) method. Thirty-five healthy male volunteers took 100 mg/day aspirin for 14 days. Whole-blood aggregation was analyzed at baseline and on days 7 and 14, using collagen and adenosine diphosphate as the stimuli, and compared with the platelet-rich plasma (PRP) aggregation measured by optical aggregometer. The platelet-aggregation threshold index (PATI) for both methods, which was defined as the putative agonist-concentration giving half-maximal aggregation, and the PRP-maximal aggregation rate were analyzed. The maximal aggregation rate induced by 1.6 mg/L collagen decreased from 85.5% (80.8-92.8) [median (interquartile range)] at baseline to 51.5% (39-63.8) on day 14 (p<0.0001). The PRP-PATI and whole-blood PATI for collagen increased from 0.32 (0.28-0.70) to 1.82 mg/L (1.25-2.89) (p<0.0001) and from 0.28 (0.22-0.3) to 1.06 mg/L (1.01-1.29) (p<0.0001) respectively. The whole-blood PATI and PRP-PATI for collagen, as well as the maximal PRP aggregation rate, clearly distinguish platelet aggregability before and after aspirin intake. However, whole-blood analysis by the SFP-method is easier to perform, and is a promising method of monitoring aspirin's effects.

Population Pharmacodynamic Modelling of Aspirin- and Ibuprofen-Induced Inhibition of Platelet Aggregation in Healthy Subjects

The objective of this study was to develop a mechanism-based pharmacodynamic model that characterizes the antiplatelet effects of aspirin (acetylsalicylic acid) and ibuprofen alone and in combination. Ten healthy volunteers were enrolled in a single-blinded, randomized, three-way crossover study. Treatments consisted of single doses of oral aspirin (325 mg) and ibuprofen (400 mg) and concomitant administration of aspirin (325 mg) and ibuprofen (400 mg). Ex vivo whole blood platelet aggregation induced by collagen (1 microg/mL) or arachidonic acid (0.5 mmol/L) was measured by impedance aggregometry. Model development and population parameter estimation were performed using nonlinear mixed-effects modelling implemented in NONMEM. Relatively complete inhibition of platelet aggregation was achieved following aspirin treatment (approximately 77% inhibition within 2 hours), and return to baseline values occurred within 72-96 hours after dosing. In contrast, treatment with ibuprofen alone or in combination with aspirin produced transient inhibition of platelet aggregation, with complete recovery observed in 6-8 hours. The final pharmacodynamic model was based on the turnover of cyclo-oxygenase-1 (COX-1) enzyme, and incorporated irreversible inhibition by aspirin and reversible binding and antiplatelet effects of ibuprofen. The temporal response profiles from all three study arms were well described by the final model, and the parameters were estimated with good precision. The apparent turnover rate constant for COX-1 (kout) and the irreversible inhibition rate constant for aspirin (K) were estimated to be 0.0209 h(-1) and 0.152 (mg/L)(-1).h(-1), with interindividual variability of 30.6% and 26.2%, respectively. Simulations were used to evaluate the influence of clinically relevant ibuprofen regimens on the antiplatelet effect of aspirin, confirming clinical reports that the antiplatelet effect of aspirin would be blocked when multiple daily doses of ibuprofen are given, even if taken after aspirin administration. A mechanism-based pharmacodynamic model has been developed that characterizes the antiplatelet effects of aspirin and ibuprofen, alone and concomitantly, and predicts a significant inhibition of aspirin antiplatelet effects in the presence of a typical ibuprofen dosing regimen.

Flow cytometric assessment of platelet aspirin resistance using light scattering

A simple and reliable assay is needed for the prediction of the clinical efficacy of antiplatelet aspirin therapy. We have devised another method for the evaluation of platelet function and aspirin resistance (AR), via conventional flow cytometry (FCM). To devise an optimized protocol for the assessment of platelet AR, various analytic variables of FCM were investigated. Using this devised protocol, AR was assessed in healthy subjects as an example. The protocol utilized herein is as follows: citrate-anticoagulated platelet-rich plasma was mixed 1:1 with HEPES-buffered saline in two tubes, one of which is treated with aspirin. During the acquisition of FCM, arachidonate is added to the tube. The response of the aspirin-treated platelets is then compared with those of nontreated ones on a time/forward scatter plot. In the 61 total subjects, none was identified as aspirin resistant by this assay. Using light scattering, platelet aggregation and aspirin's antiplatelet effects can be readily and cost-effectively detected. According to this assay, biochemical AR appears to be rare. This new protocol may prove useful in a clinical setting or as a research tool.

Pyrazolinone analgesics prevent the antiplatelet effect of aspirin and preserve human platelet thromboxane synthesis.

Anti-inflammatory analgesics, including ibuprofen and naproxen, are known to interfere with the antiplatelet effect of aspirin, presumably as a result of a drug-drug interaction at the level of platelet cyclooxygenase-1 (COX-1). We studied whether dipyrone, which has recently been reported to inhibit COX isoforms by a mechanism different from conventional non-steroidal anti-inflammatory drugs (NSAIDs), also interferes with the antiplatelet effect of aspirin. Arachidonic acid- and collagen-induced aggregation, as well as thromboxane formation, were measured in human platelet-rich plasma. Platelet P-selectin expression was determined by flow cytometry and cell-free COX enzyme activity was quantified by luminol-enhanced luminescence of human platelet microsomes. In addition, computerized docking was performed based on the crystal structure of COX-1. 4-Methylaminoantipyrine (MAA), the active metabolite of dipyrone, largely attenuated or even completely abolished the inhibition of arachidonic acid-induced platelet aggregation, thromboxane formation and P-selectin expression by aspirin. Similar results were obtained for other pyrazolinones, as well as for the conventional NSAIDs ibuprofen and naproxen. Moreover, MAA attenuated the effect of aspirin on COX activity of platelet microsomes, suggesting a competition with aspirin at the COX-1 enzyme. This was confirmed by docking studies, which revealed that MAA forms a strong hydrogen bond with serine 530 within the COX-1, thereby preventing enzyme acetylation by aspirin. This study demonstrates for the first time that dipyrone and other pyrazolinones have a high potential to attenuate or prevent the antiplatelet effect of aspirin. This should be considered if pyrazolinone analgesics are administered to patients with cardiovascular disease requiring antiplatelet aspirin therapy.

Evaluation of Dose-Related Effects of Aspirin on Platelet Function

The antiplatelet effect of aspirin is attributed to platelet cyclooxygenase-1 inhibition. Controversy exists on the prevalence of platelet resistance to aspirin in patients with coronary artery disease and effects of aspirin dose on inhibition. Our primary aim was to determine the degree of platelet aspirin responsiveness in patients, as measured by commonly used methods, and to study the relation of aspirin dose to platelet inhibition. We prospectively studied the effect of aspirin dosing on platelet function in 125 stable outpatients with coronary artery disease randomized in a double-blind, double-crossover investigation (81, 162, and 325 mg/d for 4 weeks each over a 12-week period). At all doses of aspirin, platelet function was low as indicated by arachidonic acid (AA)-induced light transmittance aggregation, thrombelastography, and VerifyNow. At any 1 dose, resistance to aspirin was 0% to 6% in the overall group when AA was used as the agonist, whereas it was 1% to 27% by other methods [collagen and ADP-induced light transmittance aggregation, platelet function analyzer (PFA-100)]. Platelet response to aspirin as measured by collagen-induced light transmittance aggregation, ADP-induced light transmittance aggregation, PFA-100 (81 mg versus 162 mg, P < or = 0.05), and urinary 11-dehydrothromboxane B2 was dose-related (81 mg versus 325 mg, P = 0.003). No carryover effects were observed. The assessment of aspirin resistance is highly assay-dependent; aspirin is an effective blocker of AA-induced platelet function at all doses, whereas higher estimates of resistance were observed with methods that do not use AA as the stimulus. The observation of dose-dependent effects despite nearly complete inhibition of AA-induced aggregation suggests that aspirin may exert antiplatelet properties through non-cyclooxygenase-1 pathways and deserves further investigation.

Frequency of Genetic Polymorphisms of COX1 , GPIIIa and P2Y1 in a Chinese Population and Association with Attenuated Response to Aspirin

Aspirin is a frequently prescribed drug for primary and secondary prevention of myocardial infarction, stroke and cardiovascular death. However, aspirin resistance may affect up to 45% of the population. Little is known on the role of genetic factors that contribute to resistance or augmented response to aspirin in different human populations. In a large sample of nonsmoker, medication-free healthy volunteers from mainland China (n = 323; age: 22.1 +/- 2.0 years) (mean +/- standard deviation), we determined the frequency of polymorphisms in cyclooxygenase 1 (COX1) (A-842G and C50T), glycoprotein IIIa (GPIIIa) (PLA1/A2) and purinergic receptor P2Y (P2Y1) (C893T and A1622G) genes. These candidate genes were chosen on the basis of their impact on platelet physiology and aspirin mode of action. A four panel P2Y1 genotype-stratified sample of healthy volunteers (n = 24 in total), identified from the large study sample above, prospectively received a 100 mg daily oral dose of aspirin for 7 days. We measured changes in platelet aggregation before and after aspirin treatment. As a comparison reference group, 6 out of 24 subjects in the prospective aspirin trial had the P2Y1 CT893/AG1622 genotype that displays a low frequency (<7%) in the Chinese population. COX1 A-842G, C50T and GPIIIa PLA1/A2 genetic polymorphisms were not observed in our sample from mainland China. Allele frequencies of P2Y1 893T and 1622G were 3.5 and 30.6%, respectively. The heterozygosity for the P2Y1 A1622G polymorphism observed in the present study was different to Caucasians; Chinese displayed a higher allele frequency for the 1622G allele. After aspirin treatment, the net decrease in arachidonic acid-induced platelet aggregation was significantly larger in the P2Y1 CT893/AG1622 genotype panel (83.4 +/- 3.7%, net reduction by aspirin expressed as percentage of baseline) compared with CC893/GG1622 (68.2 +/- 13.5%), CC893/AG1622 (68.9 +/- 9.6%) and CC893/AA1622 (65.1 +/- 9.1%) genotypic groups (p = 0.012, 0.025 and 0.004, respectively; statistical power = 77%). There was no significant difference in antiplatelet effect of aspirin among the CC893/GG1622, CC893/AG1622 and CC893/AA1622 genotypes (p > 0.05). The COX1 A-842G, C50T and GPIIIa PLA1/A2 polymorphisms are rare in Chinese. In contrast to previous studies in Caucasian populations, these candidate functional polymorphisms are unlikely to be significant contributors to aspirin pharmacodynamics in Chinese persons. Importantly, the presence of the P2Y1 893CC genotype appears to confer an attenuated antiplatelet effect during aspirin treatment in healthy Chinese volunteers. These data collectively underscore the importance of population-to-population variability in clinical pharmacogenetics research and provide a basis for further long-term studies of aspirin response and P2Y1 genetic variation in patients with cardiovascular risk.

Relationship between endothelial dysfunction, oxidant stress and aspirin resistance in patients with stable coronary heart disease

Interindividual variability of platelet inhibition after aspirin administration has been described. Additionally, aspirin resistance occurs in some individuals, but the mechanism for aspirin resistance is still unknown. The aim of the present study was to examine the role of endothelial dysfunction in aspirin resistance. The antiplatelet effect of aspirin was studied prospectively in 54 consecutive patients with stable coronary heart disease. Platelet aggregation rate was measured and aspirin resistance was defined by a relative inhibition of adenosine diphosphate (5 micromol/L)-induced platelet aggregation of >or=70%. Thrombomodulin (TM) and free tissue factor pathway inhibitor (TFPI) were measured as endothelial dysfunction markers. Erythrocyte superoxide dismutase activity, plasma level of vitamin C, vitamin E and lipoperoxide were measured to estimate the oxidative stress. Platelet aggregation was positively correlated with TM (r = 0.277, P < 0.05) and TFPI (r = 0.288, P < 0.05) respectively. The TFPI level in aspirin-resistant patients (119.5 +/- 13.5 ng/mL) was significantly higher than that in aspirin-sensitive patients (107.8 +/- 18.9 ng/mL; P < 0.05). There were no statistically significant differences on any indicator of oxidative stress between two groups. Endothelial dysfunction is one of the mechanisms for aspirin resistance, whereas oxidative stress may not involve in the process of aspirin resistance.

A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease

We sought to compare the results obtained from six major platelet function tests in the assessment of the prevalence of aspirin resistance in patients with stable coronary artery disease. 201 patients with stable coronary artery disease receiving daily aspirin therapy (> or =80 mg) were recruited. Platelet aggregation was measured by: (i) light transmission aggregometry (LTA) after stimulation with 1.6 mM of arachidonic acid (AA), (ii) LTA after adenosine diphosphate (ADP) (5, 10, and 20 microM) stimulation, (iii) whole blood aggregometry, (iv) PFA-100, (v) VerifyNow Aspirin; urinary 11-dehydro-thromboxane B(2) concentrations were also measured. Eight patients (4%, 95% CI 0.01-0.07) were deemed resistant to aspirin by LTA and AA. The prevalence of aspirin resistance varied according to the assay used: 10.3-51.7% for LTA using ADP as the agonist, 18.0% for whole blood aggregometry, 59.5% for PFA-100, 6.7% for VerifyNow Aspirin, and finally, 22.9% by measuring urinary 11-dehydro-thromboxane B(2) concentrations. Results from these tests showed poor correlation and agreement between themselves. Platelet function tests are not equally effective in measuring aspirin's antiplatelet effect and correlate poorly amongst themselves. The clinical usefulness of the different assays to classify correctly patients as aspirin resistant remains undetermined.

Ranitidine appears to reduce the antiplatelet effect of aspirin,

Ranitidine appears to reduce the antiplatelet effect of aspirin,

Ranitidine appears to reduce the antiplatelet effect of aspirin,

Ranitidine appears to reduce the antiplatelet effect of aspirin,

Recent FDA Warning of the Concomitant Use of Aspirin and Ibuprofen and the Effects on Platelet Aggregation

Recent FDA Warning of the Concomitant Use of Aspirin and Ibuprofen and the Effects on Platelet Aggregation