Prevalence Of Aspirin Resistance Research Articles

Abstract 4017: Reduced Anti-Platelet Response to Clopidogrel in Diabetic Patients Undergoing Percutaneous Coronary Intervention

Despite dual antiplatelet therapy with aspirin and clopidogrel, patients with diabetes mellitus (DM) suffer from frequent recurrent ischemic events. Previous studies have shown that DM patients have a higher prevalence of aspirin resistance than non-DM patients. The aim of this analysis was to determine if DM patients have a decreased antiplatelet response to either maintenance or high loading clopidogrel administration when compared to non-DM patients. One hundred and thirty eight patients that underwent percutaneous coronary intervention (PCI) in the Clear Platelets-2 Study were included in this analysis. Patients were grouped according to clopidogrel dose use and presence of DM. Subjects were either on maintenance therapy with 75mg of clopidogrel (C75 group; n=72) or received a loading dose of 600mg of clopidogrel immediately after PCI (C600 group; n=66). All patients received 325-mg aspirin. Platelet function was measured by Light Transmission Aggregometry using ADP (5 and 20μM), TRAP (15 μM), and collagen (2μg/ml). Overall, DM patients in the C75 group had higher platelet aggregation using 5 and 20μM ADP and 2μg/ml collagen. DM patients had lower relative platelet inhibition at 24hrs with 5 μM ADP and 2μg/ml collagen in the C600 group when compared to non-DM patients (Table ). DM patients undergoing PCI exhibit higher platelet aggregation when receiving standard clopidogrel maintenance dose and lower relative platelet inhibition with high clopidogrel loading dose. Higher doses of clopidogrel or more potent P2Y12 receptor antagonists may be needed in DM patients to obtain comparable platelet inhibition to non-DM patients.

Thrombogenicity in patients with percutaneous coronary artery intervention and dual antiplatelet treatment

Antiplatelet drugs are very effective and widely used for both the initial management of acute coronary syndrome and the long-term prevention of myocardial infarction, stroke, and peripheral artery disease. Dual antiplatelet therapy with clopidogrel and aspirin is more effective than aspirin monotherapy in most patients with cardiovascular disease.1,2 In addition, in patients with percutaneous coronary artery intervention (PCI), the addition of cilostazol on top of the dual antiplatelet treatment further increases clinical efficacy, as was shown in the CREST (Cilostazol for RESTenosis) trial.3 Finally, in a large randomized trial in 13 608 patients who were scheduled for PCI, prasugrel, a more potent and rapidly acting thienopyridine compound than clopidogrel, was more effective in reducing death from cardiovascular causes, non-fatal myocardial infarction, and non-fatal stroke.4 So, the degree of platelet function inhibition directly relates to clinical outcome in patients with PCI. Despite the use of more potent antiplatelet drugs, a considerable number of vascular patients have recurrent thrombotic events after PCI.5 It is thought that an ineffective response to these drugs contributes to the occurrence of these events, although the prevalence of aspirin resistance using aggregometry is only between 5.2 and 8%.6 The current literature is, … *Corresponding author. Tel: + 31205665976, Fax: + 31206968833, Email: p.w.kamphuisen{at}amc.uva.nl

Prevalence and Clinical Characteristics of Aspirin Resistance in the Patients with Type 2 Diabetes Mellitus

Background: We examined the prevalence and clinical characteristics of aspirin resistance in the Korean patients with type 2 diabetes mellitus. Methods: We studied 181 Korean patients with type 2 diabetes mellitus who were taking aspirin (100 mg/day for ≥ 3 months) and no other antiplatelet agents. The VerifyNow System was used to determine aspirin responsiveness. Aspirin resistance was defined as an aspirin reaction unit (ARU) ≥ 550. We measured the cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) to evaluate arteriosclerosis. The anthropometric parameters, electrocardiogram, blood pressure, fasting plasma glucose, lipid profiles, hemoglobin A1c, highly sensitive C-reactive protein (hsCRP), homocysteine, and microalbuminuria were measured in each patient. Results: The prevalence of aspirin resistance in type 2 diabetic patients was 9.4% (17 of 181). Those who had aspirin resistance were older than those without aspirin resistance (64.6 ± 10.6 vs. 59.8 ± 8.1, P = 0.024). Aspirin resistance was not associated with fasting plasma glucose, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, hemoglobin A1c, hsCRP, homocysteine, microalbuminuria, ABI, CAVI, and body mass index. Conclusion: Prevalence of aspirin resistance in the Korean patients with type 2 diabetes mellitus was 9.4%. Although aspirin resistance was associated with old age, we could not find any good clinical parameter to predict it. Therefore, aspirin resistance should be evaluated i n diabetic patients taking aspirin for prevention of cardiovascular complications. (KOREAN DIABETES J 32:53~59, 2008)

Aspirin Resistance in Children with Heart Disease at Risk for Thromboembolism: Prevalence and Possible Mechanisms

Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B(2) (11-dTXB(2)) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p < 0.01). 11-dTXB(2) levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB(2) levels before (7297 vs. 4160 pg/mg creatinine; p < 0.01) and after (2153 vs. 1412 pg/mg; p = 0.03) aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

Aspirin-resistant platelet aggregation in a cohort of patients with coronary heart disease

Aspirin resistance could be defined as thrombotic and embolic cardiovascular events despite regular aspirin therapy. The study aimed to determine the profile and prevalence of aspirin resistance in coronary artery disease patients. We evaluated the prevalence of aspirin resistance in a cohort of 505 patients with the diagnosis of coronary artery disease taking 80-300 mg regular aspirin daily. Platelet functions were analyzed by the Platelet Function Analyzer (PFA)-100 with collagen and epinephrine cartridges and collagen and ADP cartridges. A closure time of 186 s or less with the collagen and epinephrine cartridge was defined as aspirin resistance. Of the patients, 118 (23.4%) were aspirin resistant by the PFA-100. Aspirin-resistant patients were more likely to be older than aspirin-sensitive patients (P = 0.024). No statistically significant differences between the aspirin-resistant and aspirin-sensitive individuals were present in gender, major risk factors of coronary artery disease, number and localization of involved coronary vessels, serum lipid levels, and blood counts. According to the high prevalence of coronary heart disease, many people are affected by aspirin resistance, which may play a role in adverse cardiovascular events. Monitoring of platelet function in patients with coronary heart disease may support the optimization of antiplatelet therapy with additional and/or alternative agents.

Cardiology: Aspirin Resistance in Patients with Stable Coronary Artery Disease with and without a History of Myocardial Infarction

Aspirin therapy is a cornerstone in the prevention of atherothrombotic events, but recurrent vascular events are estimated to occur in 8-18% of patients taking aspirin for secondary prevention after 2 years. Estimates of biologic aspirin resistance vary from 5% to 60%, depending on the assay used. However, the relationship between biologic measurements of aspirin resistance and adverse clinical events remains unclear. To determine whether patients with documented myocardial infarction (MI) while on aspirin therapy (cases) were more likely to be aspirin resistant than were patients with coronary artery disease (CAD) who had no history of MI (controls) and to assess clinical predictors of aspirin resistance in patients with stable CAD. This case-control study examined aspirin responses using the VerifyNow Aspirin Assay system in 50 cases and 50 controls who had taken a dose of aspirin within 48 hours of presentation to the clinic visit. Odds ratios were estimated to determine the association between aspirin resistance and MI. Independent predictors of aspirin resistance were determined using univariate and multivariate analyses. An increase in the prevalence of aspirin resistance among cases (16% vs 12% in controls) was not observed (OR 1.40; 95% CI 0.45 to 4.37; p = 0.566). In the overall CAD population, female sex was independently associated with aspirin resistance (OR 4.01; 95% CI 1.15 to 13.92; p = 0.029). Additional large studies are required to understand whether biologically defined aspirin resistance is associated with increased risk for cardiovascular events, with special attention paid to sex differences.

“Aspirin Resistance”: Low Prevalence and Assay Discordance in a Pediatric Cohort.

“Aspirin resistance” (i.e., inadequate platelet inhibition as suggested by ex vivo assays in patients on aspirin) has been reported to occur commonly in adults and has been linked to an increased risk of adverse clinical events in this age group. However, its prevalence and clinical significance are largely unknown in children, with only limited pediatric data available. We have studied 22 children (ages 1 to 17 years) started on aspirin therapy for various indications (12 with a history of ischemic stroke, 6 after intervention via cardiac catheterization or surgery, 3 with a primary rheumatologic diagnosis, 1 with thrombocytosis) using a variety of measures of platelet inhibition, including optical aggregometry, PFA-100® and urinary thromboxane B2 concentration. We considered previously published definitions of aspirin resistance in adults, including ≥ 70% aggregation to 10 μM adenosine diphosphate (ADP) and ≥ 20% aggregation to 0.5 mg/mL arachidonic acid (AA), normal PFA-100 closure time (collagen/epinephrine cartridge) and normal urinary thromboxane B2 concentration (normal range defined by healthy pediatric controls). Subjects had received aspirin for a minimum of one week (range 1 to 249 weeks) prior to testing and mean aspirin dose was 3.4 mg/kg/d (range 1.3 to 7.9). Only 1 of 22 pediatric subjects (5%) met any of the pre-specified definitions for aspirin resistance; this single subject exhibited a normal PFA-100 closure time while receiving aspirin but was not aspirin resistant according to optical aggregometry or urinary thromboxane B2 criteria. Two other subjects on aspirin exhibited inappropriately “normal” aggregation to either ADP or AA (but not both). Each subject on aspirin excreted low levels of urinary thromboxane B2 compared with healthy non-medicated controls. To confirm an aspirin effect, five subjects were studied prior to initiation of aspirin therapy; each demonstrated pronounced changes in measured parameters after aspirin dosing (e.g. mean aggregation to AA decreased from 83 to 7%, p<.001). The small number of subjects who demonstrated any evidence of aspirin resistance did not differ from fully aspirin responsive subjects in terms of age, gender, race, platelet count, or aspirin dose, indication or therapy duration. Nor was there significant correlation between any of the measures of aspirin resistance we studied. In this initial prevalence study of a clinically diverse group of pediatric patients, laboratory evidence of aspirin resistance was not commonly encountered, despite our utilization of a broad panel of assays previously reported to identify aspirin resistance in adults. The prevalence of aspirin resistance in children thus appears low, and possibly less than that in adults. However, for the minority of pediatric patients who demonstrate laboratory evidence of aspirin resistance, this finding may hold clinical relevance; clinical follow-up of this cohort is ongoing. Finally, the lack of correlation we observed between assays previously linked to adverse clinical outcomes in patients taking aspirin supports that multiple molecular mechanisms contribute to the clinical phenotype of aspirin treatment failure.

The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events

Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events (MACE) in patients with stable coronary artery disease. The aim of our study was to determine; the prevalence of aspirin resistance in patients with acute coronary syndromes, the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects. We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome. Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 (Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP (Col/ADP) cartridges. Primary end points of the study were myocardial infarction, unstable angina, cardiac death. 19% (n = 20) of patients were aspirin resistant by PFA-100. In the follow-up, MACE occured in 9 patients (45%) with aspirin resistance and in 10 patients (11.7%) with aspirin sensitive platelet aggregation (p = 0.001). Multivariate analysis showed that aspirin resistance was an independant predictor of MACE. The prevalence of MACE in patients who were on clopidogrel treatment for 12 months were lower compared to those who were on a clopidogrel treatment for the first six months (p = 0.040). We determined that the MACE risk in patients with acute coronary syndromes having detected aspirin resistance, was higher at statistically significant levels compared to patients having aspirin sensitive platelet aggregation. Our results showed that aspirin resistance, was an independant predictor of MACE in patients with acute coronary syndrome.

5: Prevalence of Aspirin Resistance in Patients Presenting to the Emergency Department with Chest Pain

5: Prevalence of Aspirin Resistance in Patients Presenting to the Emergency Department with Chest Pain

Patients with Heart Failure Have Increased Prevalence of Aspirin Resistance: Preliminary Results from the ARTIST Trial

Patients with Heart Failure Have Increased Prevalence of Aspirin Resistance: Preliminary Results from the ARTIST Trial

Prevalence of aspirin resistance in patients with an evolving acute myocardial infarction

Objective To study the prevalence and importance of aspirin resistance in patients with an evolving acute myocardial infarction (AMI) by use of the Platelet Function Analyzer-100. Introduction Previous studies have demonstrated the existence of aspirin resistance, but the clinical relevance of the phenomenon remains to be clarified. If aspirin resistant patients comprise a high-risk subgroup, it might be expected that the prevalence of aspirin resistance in patients with AMI would be higher than in patients without AMI. We hypothesized that the prevalence of aspirin resistance in patients with AMI was twice the prevalence in patients without AMI. Methods We included 298 consecutive patients with known cardiovascular disease who were admitted to hospital with symptoms suggestive of an AMI. All had been taking aspirin 150 mg/day for at least 7 days prior to hospital admission. Platelet function was measured immediately at admission, and aspirin resistance was defined as a collagen/epinephrine Closure Time (CT CEPI) < 165 s. Results We found that 70 (23.5%) patients were aspirin resistant, and 70 (23.5%) patients ended up with the diagnosis of an AMI. The prevalence of aspirin resistance was significantly higher in patients with AMI as compared to patients without (36% versus 20%, OR 2.26, CI 95% 1.19–4.22, p = 0.0058). The CT CEPI measured at admission was an independent factor associated with an AMI. Conclusions Aspirin resistance is present in almost one fourth of patients admitted to hospital with symptoms suggestive of an AMI, and aspirin resistance is significantly associated with the diagnosis of a definite AMI.

Is aspirin effective in diabetic patients? No

Is aspirin effective in diabetic patients? No

Resistance in vitro to low-dose aspirin is associated with platelet PlA1(GP IIIa) polymorphism but not with C807T(GP Ia/IIa) and C-5T kozak (GP Ibα) polymorphisms

ObjectivesWe investigated whether three platelet gene polymorphisms, PlA1/A2, C807T, and C-5T Kozak (encoding, respectively, for platelet membrane glycoproteins (GP) IIIa, GP Ia/IIa, GP Ibα), could contribute to the resistance to a low dose of aspirin (160 mg/day). BackgroundAspirin antiplatelet effect is not uniform in all patients, and the mechanism by which some patients are in vitro resistant to aspirin remains to be determined. However, it has been suggested that polymorphisms of platelet membrane glycoproteins might contribute to aspirin resistance. MethodsNinety-eight patients on aspirin (160 mg/day) for at least one month were enrolled. Aspirin resistance was measured by the platelet function analyzer (PFA)-100 analyzer; genotyping of the three polymorphisms was performed using a polymerase chain reaction-based restriction fragment-length polymorphism analysis. ResultsUsing a collagen/epinephrine–coated cartridge on the PFA-100, the prevalence of aspirin resistance was 29.6% (n = 29). Aspirin-resistant patients were significantly more often PlA1/A1(86.2%; n = 25) than sensitive patients (59.4%; n = 41; p = 0.01). Of the 29 patients, 25 were reevaluated after having taken 300 mg/day aspirin for at least one month. Only 11 patients still have nonprolonged collagen epinephrine closure time, and these were all PlA1/A1. No relation was found between resistance status and C-5T Kozak or C807T genotypes. ConclusionsPlatelets homozygous for the PlA1allele appear to be less sensitive to inhibitory action of low-dose aspirin. This differential sensitivity to aspirin may have potential clinical implications whereby specific antiplatelet therapy may be best tailored according to the patient's PlAgenotype.

Resistance to aspirin in vitro is associated with increased platelet sensitivity to adenosine diphosphate

Background: Platelet activation plays an important role in arterial thrombosis and the widespread use of aspirin has reduced major events by 25% in the secondary prevention of cardiovascular diseases. However, it appears that aspirin antiplatelet effect is not uniform and 8–45% of the population are, in vitro, aspirin resistant, and it is well recognized that platelets can be activated by pathways that are not blocked by aspirin, such as adenosine diphosphate (ADP). Objectives: To investigate whether aspirin-resistant patients have a modified sensitivity to ADP-induced platelet activation Material and Methods: Seventy-two patients were enrolled. Platelet function was measured by the PFA-100® analyser; platelet GP IIb–IIIa activation by ADP 10 μM was assessed by flow cytometry using PAC-1 MoAb. Results: Using a collagen/epinephrine coated cartridge on the PFA-100®, the prevalence of aspirin resistance was 29.2% ( n=21). For aspirin-resistant patients, the collagen/ADP coated cartridge showed a closure time significantly shorter ( p=0.004) compared to the sensitive and control groups. Platelets from aspirin-resistant patients bound PAC-1 significantly more ( p=0.03) than the aspirin-sensitive patients and controls when activated with 10 μM ADP. Conclusions: Platelets from aspirin-resistant patients appear to be more sensitive and activable by ADP. This hypersensitivity could provide a possible explanation for the so-called aspirin resistance, and this could justify therapeutic improvement with alternative antiplatelet agents.

Profile and prevalence of aspirin resistance in patients with cardiovascular disease

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