Aspirin Resistance Research Articles

Prevalence and Clinical Predictors of Aspirin Resistance in Heart Transplant Recipients

<h3>Purpose</h3> Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Aspirin is thought to be associated with improved graft survival and reduced cardiac allograft vasculopathy in heart transplant (HT) recipients. The assessment of aspirin resistance by laboratory methods is potentially of great therapeutic importance, as it would enable identification of patients at risk for clinical events and allow intervention to prevent subsequent morbidity or mortality. We aimed to determine the prevalence and clinical predictors of aspirin resistance following HT. <h3>Methods</h3> We evaluated 67 stable HT recipients receiving antiplatelet monotherapy with aspirin (100 mg/day≥1 month). Platelets were stimulated with adenosine diphosphate (ADP) and arachidonic acid (AA), and aggregation was assessed using light-transmitted aggregometry. Aggregation was expressed as the maximal percent change in light transmittance from baseline. Aspirin resistance was defined as AA-induced platelet aggregation of ≥20%. <h3>Results</h3> Mean AA-induced aggregation was 29.6 ±24.8%. Of the total cohort, 40 patients (60%) were aspirin resistant and 27 (40%) were not. Aspirin-resistant patients had higher HbA1c values (7.7%±1.5 vs 5.3%±0.9, p<0.001) and higher prevalence of de-novo donor specific antibodies (DSA) (43 vs 11%, p=0.013). There were no differences in aspirin resistance by baseline donor and recipient characteristics (i.e., age, gender, etiology, BMI, hypertension, hemodynamics, immunosuppression). In a multivariable analysis (Figure) HbA1c and DSA were independently associated with a significantly higher risk of aspirin resistance. <h3>Conclusion</h3> Our study suggests a high rate of aspirin resistance in HT patients, which was associated with higher DSA and HbA1c levels, both known risk factors for transplant vasculopathy and survival. Further studies are needed to correlate aspirin resistance with clinical outcomes and hence to tailor therapeutic interventions.

Aspirin Resistance as a Result of Impaired Interaction of Platelets and Neutrophils in Patients with Coronary Heart Disease

Aim. To study the relationship between the levels of synthesis of reactive oxygen species (ROS) by platelets and neutrophils in patients with coronary heart disease (CHD) before and after coronary artery bypass grafting (CABG), depending on sensitivity to acetylsalicylic acid (ASA).Material and methods. The study included 95 patients with coronary artery disease who are indicated for CABG surgery. The control group consisted of 30 healthy donors. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients were received 100 mg of an enteric form of acetylsalicylic acid (ASA). Resistance to ASA was determined at the level of platelet aggregation with arachidonic acid ≥20% by optical agregometry at least at one observation point: before CABG, on 1-3 day and on 8-10 day after surgery. We evaluated the spontaneous and induced lucigenin-dependent chemiluminescence (CL) of platelets (ADP induction) and neutrophils (zymosan induction) by the exit time to maximum intensity (Tmax), maximum intensity (Imax) and area (S) under the CL curve.Results. 70.5% sensitive (sASA) and 29.5% resistant (rASA) to ASA patients were revealed. Prior to CABG, in sASA patients, the Imax of spontaneous and zymosan-induced neutrophil CL and CL platelet activity was increased relative to control values. Tmax of spontaneous platelet CL, Imax and S under the ADP-induced platelet CL curve were lower in sASA patients, if to compare with rASA patients. On the 1st and 8-10th day after CABG in sASA patients, the CL indicators of neutrophil and platelet activity also remained elevated compared to control values. On the 1st day after CABG decreased levels of S under the spontaneous CL curve of neutrophils in rASA patients was established compared with sASA patients, and increased levels of Imax and S under the curve of induced neutrophil CL were detected in comparison with the control range. In rASA patients, the values of Tmax of spontaneous platelet CL decreased in relation to the values detected in the control group and sASA patients. On the 8–10th day after CABG, most indicators of spontaneous and zymosan-induced CL neutrophils in rASA patients were also increased compared to control values. In rASA patients a positive correlation of Imax-induced CL was found (r=0.83) on the 1st day after CABG and negative correlations of Tmax of spontaneous CL (r=- 0.75) and S under the curve induced CL (r=-0.70) on the 8-10th day were detected between platelets and neutrophils.Conclusion. In sASA patients with coronary heart disease before and after CABG, a high level of synthesis of superoxide radical by neutrophils and platelets was detected. The relationship between the levels of the synthesis of superoxide radical by neutrophils and platelets was found only after CABG in rASA patients. Increased synthesis of superoxide radical due to metabolic and regulatory relationships in neutrophils and platelets stimulates pro-inflammatory processes in coronary artery disease and determines the sensitivity of platelets to ASA.

Unfavorable Changes of Platelet Reactivity on Clopidogrel Therapy Assessed by Impedance Aggregometry Affect a Larger Volume of Acute Ischemic Lesions in Stroke.

Background: High on-treatment platelet reactivity or its equivalent—resistance to the antiplatelet agent—significantly reduces the efficacy of the therapy, contributing to a negative impact on stroke course. Previous studies demonstrated that aspirin resistance is associated with a larger size of acute ischemic infarct. Due to the increasing use of clopidogrel in the secondary prevention of stroke, we aimed to assess the impact of clopidogrel resistance on the size and extent of ischemic lesions, both acute and chronic. Methods: This prospective, single-center and observational study involved 74 ischemic stroke subjects, treated with 75 mg of clopidogrel. We used impedance aggregometry to determine platelet reactivity 6–12 h after a dose of clopidogrel as a first assessment and 48 h later as the second measurement. A favorable dynamics of platelet reactivity over time was the decrease in the minimum value equal to the median in the entire study. The volume of acute ischemic infarct was estimated within 48 h after onset in diffusion-weighted imaging and fluid-attenuated inversion recovery sequences of magnetic resonance and the severity of chronic vascular lesions by Fazekas scale. Results: Subjects with mild severity of chronic vascular lesions (Fazekas 1) exhibited a significant decrease of platelet reactivity over time (p = 0.035). Dynamics of platelet reactivity over time differed between subjects with large, moderate, mild and insignificant size of acute ischemic lesion (Kruskall-Wallis H = 3.2576; p = 0.048). In multivariate regression models, we reported unfavorable dynamics of platelet reactivity alone and combined with a high initial value of platelet reactivity as independent predictors of higher risk of a significant ischemic infarct volume (OR 7.16 95%CI 1.69–30.31, p = 0.008 and 26.49 95%CI 1.88–372.4, p = 0.015, respectively). Conclusions: We emphasized that unfavorable dynamics of platelet reactivity over time during clopidogrel therapy in acute phase of stroke affect the volume of acute infarct and the severity of chronic vascular lesions.

Low miR-19b-1-5p Expression Is Related to Aspirin Resistance and Major Adverse Cardio- Cerebrovascular Events in Patients With Acute Coronary Syndrome.

BackgroundBecause of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR‐19b‐1‐5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio‐cerebrovascular (MACCE) events in patients with ACS.Methods and ResultsIn this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR‐19b‐1‐5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow‐up time of 1.01±0.43 years. Low miR‐19b‐1‐5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (‐Log‐miR‐19b‐1‐5p, [unstandardized beta, 44.50; 95% CI, 2.20–86.80; P<0.05]), even after adjusting for age, sex, ethnicity, and prior history of stroke. Lower miR‐19b‐1‐5p expression was independently associated with a higher risk of MACCE (‐Log‐miR‐19b‐1‐5p, [hazard ratio, 1.85; 95% CI, 1.23–2.80; P<0.05]). Furthermore, a significant interaction was noted between the inverse miR‐19b‐1‐5p expression and family history of premature coronary artery disease (P=0.01) on the risk of MACCE.ConclusionsLower miR‐19b‐1‐5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR‐19b‐1‐5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.

Biochemical aspirin resistance in acute stroke patients and its association with clinical factors: aprospective pilot study.

Aspirin is still widely used in treatment and prevention of cardiovascular diseases. To predict which patients cannot benefit from aspirin due to aspirin resistance remains agreat clinical challenge. Fifty one acute stroke/transient ischemic attack (TIA) patients (ASG) with ahistory of regular aspirin intake for the previous 7 days or more were included to the study within 24 hours of symptoms onset. Twenty nine patients admitted to our department for other reasons were the controls (CG). Each patient underwent routine blood tests (white blood cells, platelets, total cholesterol, C-reactive protein) and additional blood test: glycated haemoglobin (HbA1c), insulin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Biochemical aspirin resistance was measured using the VerifyNow Aspirin platelet function analyzer. There were 9 aspirin resistance patients in ASG (17.5%) and 3 in CG (10.3%) (p = 0.38). There were no differences in either age or gender between those groups. Twelve aspirin-resistant patients differed from aspirin nonresistant patients in age, NT-proBNP and total cholesterol levels (univariate model, p = 0.004, 0.04, 0.02, respectively). In amultivariate model patients aged 76 years and more would likely to be aspirin resistant with odds ratio = 9 (95% confidence interval: 1-78). Patients aged 76 and more can be more likely aspirin resistant than younger patients. We believe that especially in the elderly with congestive heart failure there is astrong need for further investigations in this field, including searching for alternative antiplatelet therapies.

Antiplatelet Direncinin Miyokard İnfarktüsü Sonrası Sol Ventrikül Trombüsü Gelişimine Etkisi: Prospektif, Gözlemsel, Vaka-kontrol Çalışması

Objective: Left ventricular (LV) thrombus is a serious complication of acute myocardial infarction (MI). In this study, the effect of biochemical resistance to antiplatelet agents used after ST elevation MI on LV thrombus development was investigated. Material and Methods: Patients who were diagnosed with anterior MI and undergone primary percutaneous coronary intervention were included in this study. The patients were divided into two groups: Patients with thrombus (Group 1) and the patients without thrombus (Group 2). PFA-100 platelet analyzer was used to measure platelet reactivity. Clopidogrel resistance was defined as collagen adenosine 5-diphosphate closure time (COLL/ADP CT) <120 seconds and acetylsalicylic acid (ASA) resistance was defined as collagen epinephrine closure time (COLL/EPI CT) <180 seconds. Group 1 and Group 2 were compared with ASA and clopidogrel resistance. Results: The mean CT for COLL/EPI was similar in two groups (Group 1: 221.4±64.8 sec, Group 2: 217.7±70.2 sec; p=0.81). ASA resistance was detected in 24 (26.7%) patients in the whole patient group. There was no difference between the two groups in terms of ASA resistance [8 patients (26.7%) in Group 1, 16 patients (26.7%) in Group 2; p=1.0]. The mean closure times for COLL/ADP were similar in two groups (Group 1: 145.9±63.9 sec, Group 2: 155.9±63.9 sec; p=0.48). Clopidogrel resistance was detected in 27 (30%) patients in the whole patient group. There was no difference between two groups in terms of clopidogrel resistance [9 (30%) patients in Group 1, 18 (30%) patients in Group 2; p=1.0]. There was no difference between two groups in patients with both clopidogrel and aspirin resistance. Conclusion: In vivo resistance to dual antiplatelet therapy does not appear to be an effective mechanism in the development of LV thrombus after MI.

Performance comparison of aspirin assay between Anysis and VerifyNow: Assessment of therapeutic platelet inhibition in patients with cardiac diseases

BACKGROUND:Assessment of platelet inhibition for aspirin therapy is important to manage patients who are at potential risk of developing thrombotic and hemorrhagic complications.OBJECTIVE:This study aimed to evaluate a new platelet assay (Anysis-aspirin), compare it with VerifyNow-aspirin in patients with cardiac diseases, and analyze the aspirin resistance rates between the two devices.METHODS:Citrated blood samples were collected from patients with cardiac diseases referred for the aspirin response test. In the Anysis assay, a test result was provided with a blood flow migration distance (MD) until blood flow stoppage, which was comparable to aspirin reaction units (ARUs) obtained using VerifyNow. The measurements were simultaneously conducted using the two devices and compared.RESULTS:The MD without and with aspirin use was 160±33 and 254±23 mm, respectively (p < 0.0001). Compared with VerifyNow (reference), the sensitivity and specificity of Anysis-200 were 96.3 and 90.3%, respectively (area under the curve, 0.968). Furthermore, the aspirin resistance rate in aspirin-administered patients was 20.9%using VerifyNow and 16.5%for Anysis-200. The Cohen’s kappa coefficient between the two devices was 0.81, indicating an almost perfect agreement between the two devices.CONCLUSIONS:Anysis-aspirin, a novel aspirin assay for assessing platelet inhibition, showed excellent agreement with VerifyNow-aspirin with high accuracy and precision. The Anysis-aspirin assay would be used as a point-of-care test to assess aspirin non-responsiveness and abnormal platelet reactivity.

Chronic Application of Low-Dose Aspirin Affects Multiple Parameters of Three Blood Cellular Types and Antithrombin Activity: A 1:1:1 Propensity Score Matching Analysis

The mechanisms of aspirin antithrombotic actions have not been fully elucidated. We re-analyzed the data from the project Aspirin Resistance in Patients with Ischemic Atherothrombotic Diseases from April 2008 to June 2010. A total of 530 subjects were classified into 3 groups, including 40 patients without aspirin use, 24 patients taking 25-50 mg/d aspirin, and 466 patients taking 75-100 mg/d aspirin over 1 month. By 1:1:1 propensity score matching adjusting 15 primary clinical covariates, 51 patients (n = 17 per group) comprised the final sample. Hemostasis-related parameters and high platelet reactivity as measured by arachidonic acid-induced and adenosine diphosphate-induced light transmission aggregometry were compared in the 3 groups. A dose-dependent relationship was observed between aspirin and decreased high platelet reactivity incidence (PAA < 0.001, PADP < 0.01, respectively), decreased monocyte ratio (P = 0.052), increased antithrombin activity (P < 0.001), and increased platelet distribution width (P < 0.05). Aspirin at 25-50 mg/d is related to the lowest red blood cell (RBC) count, whereas 75-100 mg/d aspirin showed the highest RBC count among the 3 groups (4.52 ± 0.35 × 1012/L vs. 4.35 ± 0.57 × 1012/L vs. 4.80 ± 0.59 × 1012/L, P = 0.046). Our finding demonstrated that aspirin exerts its antithrombotic effects at least by antiplatelet function, enhancing antithrombin activity and suppressing monocytes in vivo. In addition, 3 blood cell types, namely RBCs, monocytes, and platelets, are involved in the aspirin antithrombotic mechanism. The cellular response to aspirin partially enhances the antithrombotic effects while partially inhibiting the effects.

THE VASCULAR RISK FACTORS ASSOCIATED WITH ANTIPLATELET RESISTANCE IN ISCHEMIC STROKE PATIENTS

Objectives: This research is to measure the prevalence rate of antiplatelet resistance in ischemic stroke patients and measure the vascular risk factors associated with antiplatelet resistance in patients with ischemic stroke.&#x0D; Methods and Subjects: This was a cross-sectional study with the number of respondents in this study amounted to 155 patients who all had ischemic stroke disease at Bethesda Hospital in Yogyakarta Indonesia used stroke registry to complete the data of the risk factors. VerifyNow method is used to measure the responsiveness of antiplatelet therapy.&#x0D; Results: Among the 155 patients with ischemic stroke, 45 were women (29%), 110 were men (71%), and the elderly (age more than 60 years old) in 81 patients. In total 155 patients with ischemic stroke, 106 of them have hypertensive, with diabetes are 19 patients, dyslipidemia is 90 patients, and ischemic heart disease in 13 patients. The prevalence of antiplatelet resistance in risk factors, for age more than 60 years, is 21 patients (25%, RR=1.06, *p=0.96), in diabetes is 7 patients (36%, RR=1.17, **p=0.74), dyslipidemia is 19 patients (21%, RR=0.68, ***p=0.24), and ischemic heart disease is four patients (30%). Among 127 patients, 22% (28 patients) had aspirin resistance, while from 42 patients, 26.2% (11 patients) were resistant to clopidogrel.&#x0D; Conclusion: Antiplatelet resistance is common in ischemic stroke patients. One of five patients treated with antiplatelet showed non-responsiveness. Vascular risk factors do not increase the risk of antiplatelet resistance in ischemic stroke patients.

Assessment of the impact of PTGS1, PTGS2 and CYP2C9 polymorphisms on pain, effectiveness and safety of NSAID therapies

Cyclooxygenase 1 and 2 (COX-1, COX-2) are enzymes that catalyze the first reaction in the arachidonic acid pathway. COXs are the therapeutic target for non-steroidal anti-inflammatory drugs. Inhibition of COX enzymatic activity has an analgesic, anti-inflammatory and sometimes antiplatelet effect. Single-nucleotide polymorphisms (SNPs) within genes encoding COX-1 and COX-2 (PTGS1, PTGS2) influence the risk of pain and their intensity in some diseases. They also affect the effectiveness of NSAID therapy in rheumatoid diseases. Moreover, the relationship between certain polymorphisms of PTGS2 and a higher risk of migraine and the development of aspirin resistance in the prophylaxis of cardiovascular diseases was demonstrated. The isoform of cytochrome P450, CYP2C9 has a significant influence on the efficacy and safety of NSAID use. It is responsible for the metabolism and speed of removal of these drugs. The occurrence of some of its polymorphic forms is associated with a decrease in CYP2C9 enzymatic activity, leading to changes in the pharmacokinetics and pharmacodynamics of NSAIDs. The prolonged half-life and decrease in clearance of these drugs lead to serious side effects such as hepatotoxicity, nephrotoxicity, anaphylactic reactions, cardiovascular or gastrointestinal incidents. Studies on polymorphisms of cyclooxygenases and CYP2C9 may improve the safety and efficacy of NSAIDs therapy by adjusting the dose to individual polymorphic variants, as well as expanding knowledge about the pathomechanism of inflammatory diseases.

Effect of prediabetes on asprin or clopidogrel resistance in patients with recent ischemic stroke/TIA.

Diabetes mellitus (DM) had been discovered as an independent risk factor for high on-treatment platelet reactivity (HPR) in patients with ischemic stroke. However, studies on the relationship between prediabetes and the occurrence of HPR remain scarce. This study is aimed at clarifying the association between prediabetes and HPR among patients with recent ischemic stroke or transient ischemic stroke (TIA). Patients with ischemic stroke or TIA within 90days after onset were recruited consecutively. All patients were divided into three groups: DM, prediabetes, and normal glucose tolerance according to fasting glucose, HbA1c, or OGTT. Three months later, all patients were performed platelet aggregation inhibition test and screened for high on-treatment platelet reactivity. The effect of prediabetes on HPR was analyzed in a multivariable logistic regression model. This study recruited 237 patients with ischemic stroke or TIA, including 57 cases with prediabetes, 108 with DM, and 72 with normal glucose tolerance. Aspirin and/or clopidogrel resistance was discovered in 28 cases among prediabetes group, which was significantly more frequent than normal glucose tolerance group(49.1% versus 33.3%, P = 0.046). After adjusting for confounding factors, prediabetes was found as an independent risk factor for high on-treatment platelet reactivity (HPR) among patients with recent ischemic stroke or TIA (odds ratio 2.92; 95% CI, 1.29 to 6.63, P = 0.01). Prediabetes was an independent risk factor for high on-treatment platelet reactivity in patients with recent ischemic cerebrovascular disease. Patients with prediabetes should be highlighted for the efficacy test of antiplatelet drugs.

A Narrative Review of Aspirin Resistance in VTE Prophylaxis for Orthopaedic Surgery.

Total hip arthroplasties (THA) and total knee arthroplasties (TKA) confer one of the highest risks for developing venous thromboembolism (VTE) and pharmacological prophylaxis is imperative to help mitigate the risks. Aspirin is the most cost-effective medication for VTE prophylaxis, and its use post-THA/TKA has grown in popularity. Aspirin resistance is categorised as clinical or laboratory resistance with obesity, advancing age, diabetes mellitus, dyslipidaemia and inflammatory diseases identified as risk factors for aspirin resistance. Treatment failure due to aspirin resistance has been reported in cardiovascular and cerebrovascular disease leading to increased rates of mortality and re-embolisation. However, aspirin resistance in patients undergoing a THA/TKA has not been described, nor has there been investigation into the incidence rates or clinical outcomes. The aim of this narrative review is to appraise the concept of aspirin resistance in the context of aspirin use for VTE prophylaxis after THA/TKA surgeries. This is important to investigate as the risk factors for aspirin resistance, including obesity, advancing age, diabetes mellitus, dyslipidaemia and inflammatory diseases, are also risk factors for THA/TKA and risk factors for VTE. The presence of aspirin resistance in patients undergoing orthopaedic surgery may place patients at greater risk of thrombotic events if aspirin is prescribed for VTE prophylaxis. This could further increase the risk of complications associated with VTE and potential long-term consequences such as post-thrombotic syndrome. Future research is required to explore and quantify the rates of aspirin resistance and the clinical outcomes in orthopaedic patients; especially in those patients with these overlapping risk factors for THA/TKA, VTE and aspirin resistance.

ASPIRIN RESISTANCE IN PATIENTS WITH OSA: ARISA TRIAL

SESSION TITLE: New Insights Into the Relationship Between OSA and Cardiovascular Disease SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: Obstructive sleep apnea (OSA) is one of the leading independent risk factors associated with cardiovascular events. Untreated OSA is associated with endothelial dysfunction and platelet hyperactivity through multiple metabolic, thrombotic and inflammatory pathways linked to development of cardiovascular disease. Patients with concomitant OSA and cardiovascular risks are routinely prescribed aspirin for primary and/or secondary prevention; however, it is proposed this population carries higher risk of aspirin therapy resistance. Proposed mechanisms of aspirin resistance include increased platelet turnover, gene polymorphisms (COX-1, COX-2, GPIIb/IIIa), decreased aspirin-mediated acetylation, and prothrombotic effects of leptin – all shared mechanisms with OSA. We hypothesized that compliant use continuous positive airway pressure (CPAP) therapy, which is known to improve endothelial function and decrease platelet hyperactivity may improve endothelial function and aspirin responsiveness in this population. METHODS: In Phase 1, prevalence of aspirin resistance was determined in a group of OSA patients (n=59) on daily low-dose aspirin utilizing the VerifyNow Aspirin laboratory test. Aspirin resistance was defined as aspirin reaction units (ARU) ≥ 550. In Phase 2, aspirin responsiveness, stratified by pre-CPAP endothelial function determined by two methods, the VerifyNow Aspirin laboratory test and the non-invasive EndoPAT200. The measures were obtained before and after initiation of CPAP therapy in a cohort of aspirin-naïve patients with newly diagnosed OSA (n=18). Statistical significance was set as p<0.1. Aspirin resistance was defined as aspirin reaction units (ARU) ≥ 550. Endothelial dysfunction was defined as RHI <1.67. RESULTS: In Phase 1, aspirin resistance occurred in 17% of study subjects. In Phase 2, utilization of CPAP therapy was associated with significant improvement in endothelial function (p=0.03). In subjects with endothelial dysfunction pre-CPAP (44%), initiation of CPAP therapy was associated with significant decrease in mean ARU from 563 to 520 (p=0.09). Meanwhile, in subjects with normal endothelial dysfunction, ARU decreased insignificantly, from 574 to 566 (p=0.4). Control group was not part of data analysis due to limited number of subjects. CONCLUSIONS: Although a limited study due to sample size, aspirin resistance was prevalent among our cohort of OSA patients. Initiation of CPAP therapy was associated with significant improvement in aspirin responsiveness when endothelial dysfunction was present pre-CPAP therapy. CLINICAL IMPLICATIONS: The role of endothelial dysfunction and aspirin resistance should be explored in further studies that focus on the effect of CPAP and cardiovascular outcomes. DISCLOSURES: No relevant relationships by Rakhee Agarwal, source=Web Response No relevant relationships by Jose Mendez, source=Admin input No relevant relationships by Maria Scinico, source=Web Response No relevant relationships by Oleg Sostin, source=Web Response

Long Non-Coding RNA H19 Positively Associates With Aspirin Resistance in the Patients of Cerebral Ischemic Stroke.

Background and purposeAspirin is a novel anti-platelet drug that is intensively recommended for the prevention and treatment of cerebral ischemic stroke. However, the existence of aspirin resistance weakens the effects of aspirin and usually induces the recurrence of ischemic stroke. While the mechanism underlying aspirin resistance is still unclear. Long non-coding RNA H19 (H19) is closely associated with the onset and prognosis of cerebral ischemic stroke. Since the relationship between H19 and aspirin resistance have never been reported, herein, we aimed to evaluate the H19 expression in aspirin-resistant ischemic stroke patients and subsequently, ascertain the ability of H19 to diagnose aspirin resistance.MethodsWe included 150 patients with acute cerebral ischemic stroke who were followed up for one year to determine stroke recurrence. Levels of 11-dehydro thromboxane B2 (11dhTXB2) in urine were tested to evaluate the status of aspirin resistance, and those of H19 and 8-iso-prostaglandin-2α in plasma were assessed. The relationship between 11dhTXB2 or and 8-iso-prostaglandin-2α and H19, and the receiver operating characteristic curve of H19, the association of H19 and aspirin resistance with the recurrence of stoke were statistically analyzed.ResultsPlasma H19 was significantly up-regulated in patients with aspirin resistance (p=0.0203), and the H19 levels were positively associated with urine 11dhTXB2/creatinine (R=0.04364, p=0.0106) and positively associated with the level of 8-iso-PGF2α (R=0.04561, p=0.0089). The ROC curves indicated that H19 can sensitively and specifically diagnose aspirin resistance (area under the curve, 0.8005; 95% CI, 0.7301–0.8710; p < 0.0001; specificity, 75.86207%; sensitivity, 73.84615%.). H19 is an independent risk factor for aspirin resistance (OR=1.129, p=0.0321), and aspirin resistance and H19 are closely related with ischemic stroke recurrence.ConclusionsH19 is closely associated with aspirin resistance, and H19 probably induces aspirin resistance through increasing the production of 8-iso-prostaglandin-2α. Besides which, H19 may serve as a serological marker for diagnosing aspirin resistance with high specificity and sensitivity, and the test of H19 could give clues to the recurrence of ischemic stroke.

Remote platelet function testing using P-selectin expression in patients with recent cerebral ischaemia on clopidogrel

BackgroundAntiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients, in part because of treatment resistance. The primary aim was to assess the proportion of patients...

Performance comparison of platelet function analyzers in cardiology patients: VerifyNow and Anysis-200 aspirin assays.

Analysis of responsiveness to antiplatelet therapy is crucial in the management of patients with cardiovascular diseases. This study aimed to evaluate a new platelet function analysis system (Anysis-200) and to compare it with VerifyNow (Accumetrics, San Diego, CA, USA) in cardiology patients. Overall, 125 citrated blood samples were collected from 85 cardiology patients referred for platelet function testing. In Anysis-200, platelet function was measured as blood migration distance (MD) until clogging of flow passage, which is comparable to aspirin resistance units obtained using VerifyNow. The two devices were simultaneously used and compared. The MDs before and after taking aspirin were 175±51 and 247±27 mm, respectively (p < 0.0001). Compared with VerifyNow (reference), the sensitivity and specificity of Anysis-200 was 91.5% and 75.5%, respectively (area under the curve, 0.829). Further, the true positive rate in patients newly taking aspirin was 85% for VerifyNow and 92.5% for Anysis-200, respectively. The Cohen's kappa coefficient between the two devices was 0.682, indicating a relatively high agreement. Anysis-200, a novel system for assessing platelet aggregation, has accuracy and precision equivalent to that of, and significant agreement with, VerifyNow. Anysis-200 may be useful in screening patients with abnormal platelet reactivity and aspirin nonresponsiveness.

Incidence of aspirin resistance is higher in patients with acute coronary syndrome and atrial fibrillation than without atrial fibrillation.

In patients with atrial fibrillation, standard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is the standard of care after percutaneous coronary intervention (PCI). While this therapy reduces the risk of thrombosis and stroke, it increases the risk of bleeding. It is unclear whether the antiplatelet effect of aspirin and clopidogrel may worsen atrial fibrillation (AF). OBJECTIVE Thus we aimed to analyze platelet aspirin resistance (AR) and clopidogrel resistance (CR) in acute coronary (ACS) patients based on sinus rhythm (SR) and AF. METHODS In this prospective trial, we included 543 patients (mean age: 62± 12 years; range: 26 - 89 years) who were on aspirin and clopidogrel therapy after the diagnosis of acute coronary syndrome. AR and CR were analyzed by a Multiplate® MP-0120 device by using the method of whole blood aggregometry. RESULTS AF patients had significantly higher age, mean platelet volume, and High-Sensitivity C-Reactive Protein (p< 0.01 for each parameter). Similarly, Arachidonic-acid induced (ASPI) aggregation was higher in AF patients compared to SR patients (666±218 vs. 187±179, p<0.001). Among the ACS patients, significantly more female patients had AF (p<0.001). The incidence of hypertension in the AF group was higher compared to the SR group (p<0.001). However, adenosine diphosphate levels were not at a significant level in the two groups. CONCLUSION Our findings indicate that the platelet inhibitory effect of Aspirin was worse for patients with AF, suggesting that the effectiveness of aspirin may be less in the prophylaxis of thromboembolism and more a bleeding risk.

Prevalence and Features of Aspirin Resistance in Patients with Coronary Artery Disease

Purpose. To determine the frequency of development of aspirin resistance in patients with coronary heart disease and to identify risk factors for the development of resistance to acetylsalicylic acid (ASA) in patients with coronary heart disease. Material and Methods: 96 patients were enrolled in this study with stable forms of ischemic heart disease who received a standard dose of aspirin 75 mg/day for a long time. Patients were divided into 4 groups according to the prescription of ASA. Group 1 consisted of patients who did not receive aspirin, the second group consisted of patients taking aspirin up to 1 year, the third group consisted of patients taking aspirin from 1 year to 5 years, and the fourth group included patients taking aspirin for more than 5 years. An addition, according to the results of determining aspirin resistance, the patients were divided into 2 groups. Platelet aggregation was measured using a laser analyzer: adenosine diphosphate (ADP) with 1.0 and 5.0 μmol was used. Resistance criterion: ADP ≥72% at 5.0 μmol. Results: 17.7% of patients who took aspirin in a standard dose of 75 mg/day were resistant to aspirin, and a third of them took aspirin for more than 5 years. According to the results of a study of platelet aggregation activity, the average degree of platelet aggregation with 5.0 μmol of ADP was 82.4% in patients with no reaction to aspirin. An inadequate response to aspirin was reliably often observed in women and the elderly (58.8% and 70.5%). When analyzing the results of routine laboratory studies in patients with aspirin resistance, there was a tendency to higher levels of cholesterol and glucose (p˂0.05). Possible risk factors for the development of ASA resistance are hypercholesterolemia and hyperglycemia, since aspirin resistance was more common in patients with diabetes (13 out of 17) and obesity (11 out of 17).Conclusion: High rates of ADP-induced platelet aggregation were obtained in ¼ patients with coronary heart disease. A

Biochemical Aspirin Resistance and Clinical Outcome in Indian Patients with Ischemic Stroke (2537)

Biochemical Aspirin Resistance and Clinical Outcome in Indian Patients with Ischemic Stroke (2537)

Prevalence and Clinical Predictors of Aspirin Resistance in Heart Transplant Recipients

Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Aspirin is thought to be associated with improved graft survival and reduced cardiac allograft vasculopathy in heart transplant (HT) recipients. The assessment of aspirin resistance by laboratory methods is potentially of great therapeutic importance, as it would enable identification of patients at risk for clinical events and allow intervention to prevent subsequent morbidity or mortality. We aimed to determine the prevalence and clinical predictors of aspirin resistance following HT. We evaluated 67 stable HT recipients receiving antiplatelet monotherapy with aspirin (100 mg/day≥1 month). Platelets were stimulated with adenosine diphosphate (ADP) and arachidonic acid (AA), and aggregation was assessed using light-transmitted aggregometry. Aggregation was expressed as the maximal percent change in light transmittance from baseline. Aspirin resistance was defined as AA-induced platelet aggregation of ≥20%. Mean AA-induced aggregation was 29.6 ±24.8%. Of the total cohort, 40 patients (60%) were aspirin resistant and 27 (40%) were not. Aspirin-resistant patients had higher HbA1c values (7.7%±1.5 vs 5.3%±0.9, p<0.001) and higher prevalence of de novo donor-specific antibodies (DSA) (43 vs 11%, p=0.013). There were no differences in aspirin resistance by baseline donor and recipient characteristics (i.e., age, gender, etiology, BMI, hypertension, hemodynamics, immunosuppression). In a multivariable analysis (Figure) HbA1c and DSA were independently associated with a significantly higher risk of aspirin resistance. Our study suggests a high rate of aspirin resistance in HT patients, which was associated with higher DSA and HbA1c levels, both known risk factors for transplant vasculopathy and survival. Further studies are needed to correlate aspirin resistance with clinical outcomes and hence to tailor therapeutic interventions.