Prevalence of risk factors for venous thromboembolism and aspirin resistance in Australian patients undergoing total hip and knee arthroplasty.

INTRODUCTION: Aspirin is used for venous thromboembolism (VTE) prophylaxis after total hip and knee arthroplasty (THA/TKA). However, its efficacy is unclear in patients with multiple VTE risk factors and at risk of aspirin resistance (AR). BACKGROUND AND AIMS: To determine the prevalence of risk factors for VTE and AR in patients after THA/TKA and to determine the relationship between risk factors and drugs prescribed for thromboprophylaxis. METHODS: A retrospective cohort study of elective-THA/TKA in six Australian hospitals over a 1-year period. Medical records were manually reviewed to determine demographics, thromboprophylaxis regimen and presence of risk factors. The relationship between individual and cumulative risk factors with the thromboprophylaxis regimen was determined. RESULTS: In total, 1011 patients were included with a mean (SD) age of 65.9 (±11.0) years, and 56.4% were female. The five most prevalent risk factors were obesity (59.1%), age ≥65 years (58.2%), hypertension (45.3%), dyslipidaemia (35.9%) and diabetes (19.7%). Most patients had ≥1 risk factor for VTE (93.6%) and AR (93.6%), with 49.0% and 35.0% having ≥3 concurrent VTE and AR risk factors, respectively. The only significant relationship between risk factors and drugs was diabetes (P < 0.01). Rivaroxaban was more commonly used as the number of concurrent VTE risk factors increased (P < 0.05). CONCLUSION: Patients had a high prevalence of VTE and AR risk factors, suggesting aspirin may not be beneficial in many patients. Only diabetes was linked to the selection of thromboprophylaxis. Patients who received rivaroxaban had a greater average number of VTE risk factors. Guidelines should promote individualised prescribing in higher-risk patients.

Analysis of Platelet Function Testing in Children Receiving Aspirin for Antiplatelet Effects.

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18 years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6 months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8 years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6 mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children.

DNA methylation profile in the whole blood of acute coronary syndrome patients with aspirin resistance.

BACKGROUND: Aspirin resistance (AR) results in major adverse cardiovascular events, and DNA methylation might participate in the regulation of this pathological process. METHODS: In present study, a sum of 35 patients with AR and 35 non-AR (NAR) controls were enrolled. Samples from 5 AR and 5 NAR were evaluated in an 850 BeadChip DNA methylation assay, and another 30 AR versus 30 NAR were evaluated to validate the differentially methylated CpG loci (DML). Then, qRT-PCR was used to investigate the target mRNA expression of genes at CpG loci. Finally, Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to reveal the enriched pathways. RESULTS: The AR and NAR groups displayed significant differences in DNA methylation at 7707 positions, with 270 hypermethylated sites (e.g., cg09555818 located in APOC2) and 7437 sites hypomethylated sites (e.g., cg26828689 located in SLC12A5). Six DML were validated by pyrosequencing, and it was confirmed that DNA methylation (cg16391727, cg21008208, cg21293749, and cg13945576) was related to the increasing risk of AR. The relative mRNA expression of the ROR1 gene was also associated with AR (p = 0.007), suggesting that the change of cg21293749 in DNA methylation might lead to differential ROR1 mRNA expression, ultimately resulting in AR. Furthermore, the identified differentially methylated sites were associated with the molecular pathways such as circadian rhythms and insulin secretion. CONCLUSION: Hence, the distinct DNA methylation might play a vital role in the biological regulation of AR through the pathways such as circadian rhythms.

Does proton pump inhibitor reduce the antiaggregant efficacy of aspirin in ischemic stroke?

OBJECTIVE: To evaluate the effect of using acetylsalicylic acid (aspirin) together with lansoprazole in the secondary prevention of ischemic stroke. MATERIALS AND METHODS: 199 patients with a diagnosis of ischemic stroke and transient ischemic attack (TIA) using 100 mg aspirin regularly were included in the study. All patients were evaluated for the presence of aspirin resistance before starting the study. 57 patients with aspirin resistance were excluded from the study. The remaining 142 patients were divided into two groups: the 1st group consisted of those with stomach discomfort and the 2nd group consisted of those without stomach discomfort. Patients in group 1 were given 30 mg of lansoprazole taken before breakfast in addition to aspirin therapy. All patients were re-evaluated for the presence of aspirin resistance at a one-month follow-up. The antiaggregant activity was evaluated by the impedance aggregometry method in both groups. RESULTS: Of 142 patients, 75 were in group 1, and 67 were in group 2. There was no difference between the two groups in terms of age and gender distribution of vascular risk factors. There was no statistically significant difference between the two groups in terms of aspirin efficacy. The dose of aspirin was increased in patients with aspirin resistance (AR). CONCLUSION: The combination of 30 mg lansoprazole and 100 mg aspirin does not cause a decrease in antiaggregant activity in the early period, but chronic use was not evaluated in this study. Patients with AR may benefit from an increase in the dose of aspirin.

The Diabetic Platelets.

This communication describes the platelet morphology and physiology noted in persons with diabetes and its complications. It reviews the effects of glucose lowering drugs on platelet function, and summarizes the role of anti-platelet drugs in diabetes management.

Editor's Choice - Association Between Peri-OPerative Aspirin ResisTance and CardioVascular Outcome (POPART-CVO): a Prospective Non-Interventional Cohort Study.

OBJECTIVE: New onset aspirin resistance during surgery, known as peri-operative aspirin resistance, is observed in up to 30% of vascular surgery patients and is associated with post-operative myocardial damage; questioning aspirin effectiveness towards peri-operative cardiovascular events. The objective of this study was to prospectively evaluate whether peri-operative aspirin resistance in vascular surgery is associated with an adverse cardiovascular outcome. METHODS: Based on a sample size calculation, 194 adult elective vascular or endovascular surgery patients receiving aspirin were analysed in this prospective, single centred, non-interventional cohort study. Platelet function was measured before surgery, one hour after incision, four hours post-operatively, and on the morning of the first and second post-operative days using the Multiplate analyser. The primary outcome was myocardial injury after non-cardiac surgery (MINS). Secondary outcomes included major bleeding, admission to intensive care unit, length of hospital stay, and major adverse cardiac and cerebrovascular events. Subgroup analyses were performed for patients with different cardiovascular risk and for patients who underwent endovascular surgery. RESULTS: Peri-operative aspirin resistance was observed in 27.8% of patients but was not associated with MINS (27.8% vs. 32.1%, aspirin resistance vs. no aspirin resistance, OR 0.812, 95% CI 0.406 - 1.624, p = .56) or with any of the secondary endpoints (all p > .050). In nine of the 10 subgroup analyses, aspirin resistance was not associated with a difference in MINS rate. However, in patients with a low cardiovascular risk profile (RCRI 0-2), MINS occurred more frequently in patients without aspirin resistance (p = .049). CONCLUSION: This study confirmed previous reports demonstrating that peri-operative aspirin resistance is common in patients undergoing vascular or endovascular surgery. However, in patients who continue aspirin throughout the peri-operative period, aspirin resistance is a phenomenon, which does not appear to be related to MINS. Measuring peri-operative platelet function using the Multiplate analyser with the intention to identify and potentially prevent or treat peri-operative aspirin resistance seems to be dispensable.

Platelet response to aspirin in UK and Irish pregnancy cohorts: a genome-wide approach.

A multi-center prospective cross-sectional and genome-wide association study (GWAS) recruited pregnant women taking low dose aspirin. Objectives were to (i) develop pregnancy-specific 95% reference intervals for a range of laboratory based platelet function tests (PFTs); (ii) select an optimal and acceptable PFT that reflected aspirin's COX-1 inhibition in women with confirmed aspirin adherence in pregnancy; and (iii) identify genomic variants that may influence pregnant women's platelet response to aspirin.The study included two independent cohorts of pregnant women. A range of PFTs and matched phenotyping with urinary 11-dehydrothromboxane B2 (11DTXB2) and nuclear magnetic resonance (NMR) spectroscopy detection of urinary salicyluric acid as a measure of aspirin adherence were performed. Genome-wide data was acquired from the UK Biobank Axiom® (Thermo Fisher Scientific). 11DTXB2 in combination with adherence testing with NMR salicyluric acid was an accurate and acceptable testing strategy for detecting biochemical aspirin responsiveness in pregnant women, with the provision of relevant reference ranges. GWAS meta-analysis found no significant single nucleotide polymorphisms in association with response to aspirin in pregnancy. Further evaluation in relation to effective dosing of aspirin in pregnancy and optimizing the benefits to specific subgroups should now be a priority for future research.

Aspirin resistance in infants with shunt-dependent congenital heart disease.

INTRODUCTION: Patients with cyanotic heart disease are at an increased risk of developing thrombosis. Aspirin has been the mainstay of prophylactic anticoagulation for shunt-dependent patients with several reports of prevalent aspirin resistance, especially in neonates. We investigate the incidence of aspirin resistance and its relationship to thrombotic events and mortality in a cohort of infants with shunt-dependent physiology. METHODS: Aspirin resistance was assessed using the VerifyNow™ test on infants with single-ventricle physiology following shunt-dependent palliation operations. In-hospital thrombotic events and mortality data were collected. Statistical analysis was performed to evaluate the effect of aspirin resistance on in-hospital thrombotic events and mortality risk. RESULTS: Forty-nine patients were included with 41 of these patients being neonates. Six patients (12%) were aspirin resistant. A birth weight < 2500 grams was a significant factor associated with aspirin resistance (p = 0.04). Following a dose increase or additional dose administration, all patients with initial aspirin resistance had a normal aspirin response. There was no statistically significant difference between aspirin resistance and non-resistance groups with respect to thrombotic events. However, a statistically significant incidence of in-hospital mortality in the presence of thrombotic events was observed amongst aspirin-resistant patients (p = 0.04) in this study. CONCLUSION: Low birth weight was associated with a higher incidence of aspirin resistance. Inadequate initial dosing appears to be the primary reason for aspirin resistance. The presence of both thrombotic events and aspirin resistance was associated with significantly higher in-hospital mortality indicating that these patients warrant closer monitoring.

A young patient with recurrent myocardial infarction within a half month. / åŠæœˆå† åå¤å¿ƒè‚Œæ¢—æ­»é’å¹´æ‚£è€ 1例.

In this study, we reported a young male patient with acute chest pain who was diagnosed as myocardial infarction. The regular medication was performed following coronary intervention. Under such condition, this patient had 3 times myocardial infarction within a half month. The laboratory results showed that there might be a state of hypercoagulability. Aspirin combined with clopidogrel and other treatment were administrated. Meanwhile, the examination demonstrated that there was aspirin-resistant in the patient. The antiplatelet drug and extended anticoagulation therapy were carried out. There was no further myocardial infarction, and no coronary arteries stenosis was found in the re-examination angiography. Aspirin resistance and hypercoagulability should be considered when patients occurred the repeated myocardial infarction after regular medication and coronary intervention. Replacement of the antiplatelet treatment or combination with anticoagulant therapy is necessary in similar patient to avoid the sever consequence.

Platelet function in stroke/transient ischemic attack patients treated with tocotrienol.

The purpose of this study was to characterize the effects of tocotrienol form of vitamin E (TCT) on platelet function in patients with stroke or transient ischemic attack (TIA). A double blind, randomized, single center phase II clinical trial was conducted comparing placebo (PBO) and 400 and 800 mg TCT daily for a year in 150 patients with a sentinel ischemic stroke or TIA event in the prior 6 months. Platelet function was measured at baseline and then, at 3 month intervals for a year, using light transmission aggregometry. The incidence of aspirin resistance in aspirin-treated patients or platelet inhibition in patients on clopidogrel alone was compared between the three treatment groups. Results showed that in patients taking aspirin and clopidogrel, the incidence of aspirin resistance was significantly decreased from 40% in PBO-treated patients to 9% in the 400 mg TCT group and 25% in the TCT 800 mg group (P = .03). In conclusion, patients on aspirin and clopidogrel had a higher incidence of aspirin resistance than all patients treated with aspirin alone and TCT decreased the frequency of aspirin resistance in this group.

N-Terminal Pro-Brain Natriuretic Peptide and Right Ventricular Diameter Are Related to Aspirin Resistance in Coronary Artery Disease Patients.

Background and Objectives: Resistance to ASA (ASAres) is a multifactorial phenomenon defined as insufficient reduction of platelet reactivity through incomplete inhibition of thromboxane A2 synthesis. The aim is to reassess the prevalence and predictors of ASAres in a contemporary cohort of coronary artery disease (CAD) patients (pts) on stable therapy with ASA, 75 mg o.d. Materials and Methods: We studied 205 patients with stable CAD treated with daily dose of 75 mg ASA for a minimum of one month. ASAres was defined as ARU (aspirin reaction units) ≥550 using the point-of-care VerifyNow Aspirin test. Results: ASAres was detected in 11.7% of patients. Modest but significant correlations were detected between ARU and concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) (r = 0.144; p = 0.04), body weight, body mass index, red blood cell distribution width, left ventricular mass, and septal end-systolic thickness, with trends for left ventricular mass index and prothrombin time. In multivariate regression analysis, log(NT-proBNP) was identified as the only independent predictor of ARU-partial r = 0.15, p = 0.03. Median concentrations of NT-proBNP were significantly higher in ASAres patients (median value 311.4 vs. 646.3 pg/mL; p = 0.046) and right ventricular diameter was larger, whereas mean corpuscular hemoglobin concentration was lower as compared to patients with adequate response to ASA. Conclusions: ASAres has significant prevalence in this contemporary CAD cohort and NT-proBNP has been identified as the independent correlate of on-treatment ARU, representing a predictor for ASAres, along with right ventricular enlargement and lower hemoglobin concentration in erythrocytes.

Aspirin resistance mediated by oxidative stress-induced 8-Isoprostaglandin F2.

WHAT IS KNOWN AND OBJECTIVE: Aspirin resistance refers to a patient's poor response to aspirin. There are many factors that can contribute to aspirin resistance, including single-nucleotide polymorphisms, medication compliance, drug-drug interactions and inflammation. COMMENT: Recently, oxidative stress-induced 8-isoprostaglandin F2α has attracted considerable attention because it is considered as a mechanism of aspirin resistance in many diseases, including coronary artery disease, neurology system disease, metabolic syndrome, cancer, chronic obstructive pulmonary disease and chronic kidney disease. In these diseases, increased oxidative stress may promote platelet activation and reduce the efficacy of aspirin by producing excessive amounts of 8-isoprostaglandin F2α. WHAT IS NEW AND CONCLUSION: Given the wide clinical use of aspirin, it is essential to understand why some patients do not response to it. This article reviews current research on aspirin resistance mediated by oxidative stress-induced 8-isoprostaglandin F2α.

Prevalence of aspirin resistance by thromboelastography plus platelet mapping in children with CHD: a single-centre experience.

RationaleAspirin resistance has been reported in up to 80% of children with cardiovascular defects undergoing surgery. Because of a patient who had embolic stroke while on therapeutic aspirin dose but in whom aspirin resistance was present on his thromboelastography platelet mapping, we chose to obtain thromboelastography platelet mapping on cardiac patients on aspirin to assess their risk. OBJECTIVES: This study evaluates aspirin resistance noted in these patients and their characteristics.Methods and resultsThis is a retrospective study of 25 patients taking aspirin for a month at therapeutic dose. In total, 11 female patients were enrolled. Ages in all subjects were 5 months to 27 years. A total of 19 patients had a Fontan surgery. Three had a cavopulomanary anastomosis, one had a hybrid procedure, and two had coronary anomalies. Compliance was assessed at the time of the clinic visit. Aspirin resistance was defined as platelet inhibition below 50%. Variables evaluated were level of platelet inhibition, age, body mass index, and gender.

Assessment of the relationship between platelet reactivity, vascular risk factors and gender in cerebral ischaemia patients.

AIM: Excessive activation and platelet aggregation play important roles in the aetiopathogenesis of cerebral ischaemia. The aim of this study was to assess the relationship between platelet reactivity, gender and vascular risk factors in cerebral ischaemia patients. CLINICAL RATIONALE FOR THE STUDY: The research is useful because we found high risk groups of inefficient aspirin treatment in cerebral ischaemia patients. MATERIAL AND METHODS: The study involved 101 patients, including 69 patients with ischaemic stroke and 32 patients with transient ischaemic attack. The assessment of platelet reactivity was made within 24 hours of the disease onset using two aggregometric methods: impedance and optical. RESULTS: Resistance to acetylsalicylic acid among people with cerebral ischaemia was estimated at 30.69% using impedance aggregometry and 9.2% using optical aggregometry. There were no differences in platelet reactivity or ASA resistance between the groups of patients with stroke and TIA in either method. In the whole group of patients (p = 0.04), and in the group of patients with stroke (p = 0.0143), higher reactivity of platelets was observed by impedance aggregometry in men than in women. In the whole group of patients (p = 0.0229), and in the subgroup with stroke (p = 0.0123), it was shown that aspirin resistance is significantly more common in the subgroup of men than in women. In patients suffering from nicotine addiction, significantly higher platelet reactivity was found in the whole group of patients (p = 0.004), as well as in the subgroup of patients with stroke (p = 0.0135). CONCLUSIONS: There are no differences between platelet reactivity and the incidence of aspirin resistance in patients with stroke and TIA. Male gender and smoking are associated with greater reactivity of platelets and more frequent occurrence of acetylsalicylic acid resistance in patients with cerebral ischaemia. CLINICAL IMPLICATIONS: Dual antiplatelet therapy or clopidogrel treatment should be considered in smoking males with cerebral ischaemia due to the high risk of aspirin inefficiency.

[Network pharmacology-based study on mechanisms of Danhong Injection in treatment of aspirin resistance].

This paper aims to discuss the potential targets,pathways and possible mechanisms of Danhong Injection in treatment of aspirin resistance by using network pharmacology concept and network analysis technique. Active ingredients and potential targets of Danhong Injection were collected from TCMSP database and the ingredients were further screened based on their topological characteristics. The active ingredients with nodal degree of freedom≥9 were selected as the main active ingredients. Targets related to aspirin resistance were collected from Genecards database. Drug-active ingredient-target-disease network was constructed by using Cytoscape3. 7. 0,and Funrich 3. 1. 3 software was used for gene enrichment analysis. Sixty main active ingredients were screened out from 110 active ingredients of Danhong Injection,including 51 ingredients in Salviae Miltiorrhizae Radix et Rhizoma and 11 ingredients in Carthami Flos,2 of which were both in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos. In addition,159 potential targets were collected. The results of gene enrichment analysis showed that Danhong Injection could improve aspirin resistance mainly through21 pathways involving coagulation process,inflammatory response and metabolism. This study revealed the effects of Danhong Injection for improving aspirin resistance in multi-component,multi-target and multi-pathway means mainly through regulation in coagulation process,inflammatory response and metabolism,providing more abundant information and basis for subsequent research and experimental work.

Decreased turnover aspirin resistance by bidaily aspirin intake and efficient cytoreduction in myeloproliferative neoplasms.

Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN) with an increased risk of arterial and venous thrombosis. Aspirin is recommended to reduce this risk, but resistance to antiplatelet therapy seems to hamper its efficacy in some patients. We have previously shown that multiple electrode aggregometry (MEA) was a valuable tool to assess aspirin resistance in MPN. In this study, MEA was used to assess the reduction in aspirin resistance after bi-daily (BID) aspirin intake or cytoreduction. Fifty one MPN patients (31 ET and 20 PV) receiving 75 mg aspirin once daily (OD) or BID, with or without cytoreductive treatment, were analyzed. Aspirin resistance was assessed using whole blood MEA (Multiplate®, Roche Diagnostics, Meylan, France). In all patients, global aspirin resistance consisted mainly of turnover resistance (TOR). 94% of patients with OD aspirin intake and without cytoreduction displayed biological aspirin resistance. By switching to a BID aspirin regimen, the proportion of resistant patients reduced to 47%. Cytoreduction also contributed to reduce aspirin resistance in a similar way (50% of aspirin resistant patients). Combining cytoreduction and BID aspirin regimen was the most efficient way to reduce aspirin resistance yielding to 12% resistant patients. Moreover, a nonlinear correlation was observed between TOR and naive platelet counts regardless of aspirin regimen. Last, mutational status did not seem to affect TOR. This study confirmed that BID aspirin is biologically more effective than OD aspirin in reduction of aspirin resistance. The latter was achieved through a reduction in TOR which was also decreased by cytoreductive therapy.

Association of GPIa and COX-2 gene polymorphism with aspirin resistance.

OBJECTIVE: This study aimed to explore the association between GPIa, COX-2 gene polymorphisms and aspirin resistance in the ischemic stroke patients from the southern part of Jiangsu province. METHODS: In all, 97 patients with acute ischemic stroke were enrolled in the study. GPIa gene polymorphism at 807C>T (rsl126643) locus and COX-2 gene polymorphism at -765G>C (rs20417) locus were genotyped by PCR pyrosequencing technology. Patients were divided into the aspirin sensitivity (AS) group and aspirin resistance (AR) group according to the platelet aggregation rate. The relationship between the two gene polymorphisms and aspirin resistance was investigated and analyzed. RESULTS: The distribution of the genotype (CC, CT, TT, CT + TT, and CC) and the frequency of allele T of GPIa gene at 807C>T locus were significantly different in AS and AR groups in female patients (P < .05). Logistic regression analysis showed that the genotype of CT+TT at 807C>T locus was significantly correlated with AR after adjustment for relative factors (P = .047, OR = 4.856, 95% CI: 1.020-23.108). There were no significant differences in the genotype distribution and allele frequency of the COX-2 gene -765G>C site between two groups (P > .05). CONCLUSION: GPIa gene polymorphism at 807C>T locus was associated with AR in Chinese Han females, and the expression of allele T increased the incidence of AR. The gene polymorphism of COX-2 gene at -765G>C locus was not significantly correlated with AR.

PFA-100-measured aspirin resistance is the predominant risk factor for hospitalized cardiovascular events in aspirin-treated patients: A 5-year cohort study.

WHAT IS KNOWN AND OBJECTIVE: Aspirin therapy is the clinical gold standard for the prevention of cardiovascular events. However, cardiovascular events still develop in some patients undergoing aspirin therapy. Many laboratory methods exist for measuring aspirin resistance. Using the platelet Function Analyzer (PFA)-100 system, we aimed to determine the effect of aspirin resistance on hospitalized cardiovascular events (hCVE) in a 5-year follow-up cohort. We also sought to determine the impact of aspirin resistance on the relationship between common cardiovascular risk factors and cardiovascular hospitalization. METHOD: Aspirin resistance was evaluated in aspirin-treated patients from the outpatient department. A total of 465 patients during a 5-year follow-up period were included in this study. The primary endpoint of the study was hospitalization for any acute cardiovascular event. The prevalence and associated risk factors of acute cardiovascular events were evaluated. RESULTS AND DISCUSSION: Aspirin resistance was prevalent in 91 (20.0%) of 465 patients. Prior hospitalization history of cardiovascular events was highly associated with aspirin resistance (P = .001). At the 5-year follow-up, cardiovascular events were found to have developed in 11 patients (8 stroke and 3 myocardial infarction) who exhibited aspirin resistance (12.1%) and in 9 (4 stroke and 5 myocardial infarction) patients who did not exhibit aspirin resistance (2.4%) (P < .001). At the 5-year follow-up, multivariate logistic regression analysis results showed a strong association between aspirin resistance and cardiovascular events (adjusted odds ratio 4.28; 95% CI: 1.64-11.20; P = .03). WHAT IS NEW AND CONCLUSION: PFA-100 measurements of aspirin resistance correlate with hCVE, as evidenced by both the past medical history and the 5-year follow-up. The logistic regression analysis results showed that aspirin resistance plays a larger role in hospitalized cardiovascular disease than do other cardiovascular risk factors.

[Dosage forms and doses of acetylsalicylic acid: significance for clinical practice].

The article presents a review of pharmacokinetics and pharmacodynamics of different acetylsalicylic acid (ASA) dosage forms. The review showed that efficacy and safety of ASA are determined by its systemic effects and do not depend on the dosage form. Issues of ASA resistance are discussed.

Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients.

BACKGROUND: The effect of genetic variants on aspirin resistance (AR) remains controversial. We sought to assess the association of genetic variants with AR and early clinical outcomes in patients with acute ischemic stroke (IS). METHODS: A total of 850 acute IS patients were consecutively enrolled. Platelet aggregation was measured before and after a 7-10 day aspirin treatment. The sequences of 14 variants of COX-1, COX-2, GPIb, GPIIIa, P2Y1 and P2Y12 were determined using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). The primary outcome was early neurological deterioration (END) within 10 days of admission. The secondary outcome was a composite of early recurrent ischemic stroke (ERIS), myocardial infarction (MI) and death within 10 days of admission. RESULTS: 175 (20.6%) patients were AR, 45 (5.3%) were aspirin semi-resistant, 121 (14.2%) developed END, 17 (0.2%) had ERIS, 2 (0.2%) died, and 6 (0.7%) had MI. Single locus analysis indicated that only rs1371097 was associated with AR. However, GMDR analysis indicated that the following three sets of gene-gene interactions were significantly associated with AR: rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097CT/rs2317676AG. END occurred significantly more frequently in patients with AR or high-risk interactive genotypes. Moreover, AR and high-risk interactive genotypes were independently associated with END. CONCLUSION: Sensitivity of IS patients to aspirin and END may be multifactorial and is not significantly associated with a single gene polymorphism. Combinational analysis may useful for further insight into the genetic risks for AR.