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Background: The absolute risk of recurrences among patients using aspirin for prevention of cardiovascular events remains high. Persistent platelet reactivity despite aspirin therapy might explain this in part. Reported prevalences of this so-called aspirin resistance vary widely, between 0% and 57%., Objectives: The aim of the study was to systematically review all available evidence on prevalence of aspirin resistance and to study determinants of reported prevalence., Methods: Using a predefined search strategy, we searched electronic databases MEDLINE, EMBASE, CENTRAL, and Web of Science. To be included in our analysis, articles had to contain a laboratory definition of aspirin resistance, use aspirin as secondary prevention, and report associated prevalence., Results: We included 34 full-text articles and 8 meeting abstracts. The mean prevalence of aspirin resistance was 24% (95% CI 20%-28%). After adjustment for differences in definition, used dosage, and population, a statistically significant higher prevalence was found in studies with aspirin dosage < or =100 mg compared with > or =300 mg (36% [95% CI 28%-43%] vs 19% [95% CI 11%-26%], P < .0001). Studies measuring platelet aggregation using light aggregometry with arachidonic acid as an agonist had a pooled unadjusted prevalence of 6% (95% CI 0%-12%). In studies using point-of-care platelet function-analyzing devices, the unadjusted prevalence was significantly higher, at 26% (95% CI 21%-31%)., Conclusions: Prevalences widely differ between studies reporting on aspirin resistance. Both aspirin dosage and the method of defining aspirin resistance strongly influence estimated prevalence, which explains found heterogeneity among studies. On average, it appears that about 1 in 4 individuals may express biochemically defined aspirin resistance.

Purpose of Review: Dual antiplatelet therapy (DAPT)—aspirin in conjunction with a P2Y12 inhibitor—is the cornerstone of managing patients with acute coronary syndromes post-revascularization, but the clinical response is highly variable, with potentially devastating consequences. Herein, we review the mechanisms underpinning said variability and explore emerging approaches to normalizing therapeutic benefit. Recent Findings.: The potent P2Y12 inhibitors, prasugrel and ticagrelor, exhibit minimal inter-individual variability, replacing clopidogrel in DAPT and achieving greater rates of therapeutic response. However, these benefits decline in later phases when bleeding risk begins to supersede that of ischemia. Guided de-escalation of P2Y12 inhibition as well as shortening DAPT duration have emerged as strategies that retain antithrombotic efficacy while reducing bleeding risk. Aspirin is the other component of DAPT but is also used in isolation for secondary prevention of thrombotic disease. In contrast to the P2Y12 inhibitors, genetic influences on aspirin non-response appear to be outweighed by a triad of clinical factors: non-adherence, enteric aspirin use, and inappropriate dosing according to bodyweight and BMI. Summary: Multiple de-escalation strategies for DAPT have been shown to mitigate bleeding risk, but it remains unclear which approach is ideal, necessitating head-to-head investigations to determine which exhibits the most favorable cost-to-benefit ratio. However, there is likely a role for more than one approach in clinical practice, depending on patient risk profile. Our approach to aspirin use is also in need of reassessment: strategies to improve adherence, avoidance of enteric aspirin in cardiac patients, and dose adjustment according to bodyweight and/or BMI are all likely to improve rates of therapeutic response. Moreover, platelet function testing may have a role in identifying patients expected to benefit from primary prophylactic aspirin. [ABSTRACT FROM AUTHOR]

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Southern Clinics of Istanbul Eurasia is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Aspirin (acetylsalicylic acid) is commonly prescribed to patients with a history of myocardial infarction (MI) or occlusive vascular events (e.g., stroke). Due to the complications associated with failure to follow aspirin usage guidelines, determining predictors of aspirin noncompliance in these patient populations is of clinical value and may help prevent poor outcomes. Methods: This cross-sectional study of all patients with a previously diagnosed MI was conducted over a period of 3 months from May 2015 to July 2015 at a government-based hospital in Karachi, Pakistan. Patients were administered a questionnaire that comprised two parts. Part A was designed to measure sociodemographic data including age, gender, and marital status. Part B determined whether the patient was counseled on aspirin significance, and dosage recommendation, and was participating in cardiac rehabilitation therapy. Results: A total of 456 patients included in the study. Of them, 298 (66.7%) were males. The average age was 59 (standard deviation 11) years. The outcome from univariate logistic regression revealed that with 1 year increase of age, the usage of low dose of aspirin was significantly decreased by 2%. Patients with higher education attributed a significantly different effect on the usage of aspirin. Marital status divulged no significant association with the use of different doses of aspirin. The role of rehabilitation had no effect when adjusted for age and level of education. Conclusion: Post-MI patients with higher education level and undergoing rehabilitative therapy are more likely to take low-dose aspirin as compared to those who failed to have these attributes. There is a need for carrying out further work to confirm these findings and expand our recommendations, particularly the sensitive issue regarding adequate doctor counseling among these high-risk patients. [ABSTRACT FROM AUTHOR]

Aspirin resistance can be defined as the inability of the usual dose of aspirin medication to produce its antithrombotic effect. Patients with diabetes or cardiovascular disease are at higher risk of stroke, myocardial infarction or cardiovascular death due to aspirin resistance. The aim of this bibliometric study was to identify and analyse the status and trends of aspirin resistance research production at global level through publications indexed in the Scopus database; this will shed new light on future research trends and help researchers predict dynamic direction of research. Literature search using the Scopus database was conducted to assess publications related to aspirin resistance. The selected publications included the terms related to aspirin resistance in the title, abstract or keywords. The searching was accomplished on 20 March 2016 and can be considered to include all publications up to 31 December 2015. Global cumulative publication output on aspirin resistance consists of 986 papers during 1990-2015. Among the 986 documents, 19 (1.9%) were published before 2000, 567 (57.5%) were published from 2000 to 2009 and 400 (40.6%) were published from 2010 to 2015, with peak of publications on this topic in 2008. The leading country in the field of aspirin resistance was the United States, which had the greatest counts of independent articles (165) and international collaboration articles (44). Turkey was in the second rank with 78 articles, followed by Italy (68), the UK (62) and Poland (60). The total number of citations for all documents was 26,342, and the average citations per document were 26.7. The h-index for all aspirin resistance publications was 82. This study presents the results of the first bibliometric study (including quantitative and qualitative analysis) of scientific publications in the field of aspirin renitence at global level. Aspirin resistance-related researches have notably increased in the last years, especially from 2000 to 2015. The United States is the most prolific country, not only in research quantity but also in quality. Furthermore, Turkey and European countries provided more research related to aspirin resistance than other regions such as the developing countries. [ABSTRACT FROM AUTHOR]

Although aspirin is one of the most common anti-inflammatory drugs in the world, the effect of aspirin on human skeletal muscle inflammation is almost completely unknown. This study examined the potential effects and related time course of an orally consumed aspirin dose on the inflammatory prostaglandin E2 (PGE2)/cyclooxygenase (COX) pathway in human skeletal muscle. Skeletal muscle biopsies were taken from the vastus lateralis of 10 healthy adults (5 male and 5 female, 25 ± 2 yr old) before (Pre) and 2, 4, and 24 h after (Post) a standard dose (975mg) of aspirin and partitioned for analysis of 1) in vivo PGE2 levels in resting skeletal muscle and 2) ex vivo skeletal muscle PGE2 production when stimulated with the COX substrate arachidonic acid (5 μM). PGE2 levels in vivo and PGE2 production ex vivo were generally unchanged at each time point after aspirin consumption. However, most individuals clearly showed suppression of PGE2, but at varying time points after aspirin consumption. When the maximum suppression after aspirin consumption was examined for each individual, independent of time, PGE2 levels in vivo (184 ± 17 and 104 ± 23pg/g wet wt at Pre and Post, respectively) and PGE2 production ex vivo (2.74 ± 0.17 and 2.09 ± 0.11pg·mg wet wt-1·min-1 at Pre and Post, respectively) were reduced (P < 0.05) by 44% and 24%, respectively. These results provide evidence that orally consumed aspirin can inhibit the COX pathway and reduce the inflammatory mediator PGE2 in human skeletal muscle. Findings from this study highlight the need to expand our knowledge regarding the potential role for aspirin regulation of the deleterious influence of inflammation on skeletal muscle health in aging and exercising individuals. NEW & NOTEWORTHY This study demonstrated that orally consumed aspirin can target the prostaglandin/cyclooxygenase pathway in human skeletal muscle. This pathway has been shown to regulate skeletal muscle metabolism and inflammation in aging and exercising individuals. Given the prevalence of aspirin consumption, these findings may have implications for skeletal muscle health in a large segment of the population. [ABSTRACT FROM AUTHOR]

Background: The mechanisms behind residual platelet reactivity (RPR) despite aspirin treatment are not established. It has been shown that coronary artery disease (CAD) patients with high on-aspirin RPR have elevated levels of von Willebrand factor (vWF). ADAMTS13 is a metalloprotease cleaving ultra large vWF multimers into less active fragments. Our aim was to investigate whether ADAMTS13 and vWF/ADAMTS13 ratio were associated with high RPR, and further with clinical endpoints after 2 years. Methods: Stable aspirin-treated CAD patients (n = 999) from the ASCET trial. RPR was assessed by PFA-100. ADAMTS13 antigen and activity were analysed using chromogenic assays. Endpoints were a composite of acute myocardial infarction, stroke and death. Results: The number of patients with high RPR was 258 (25.8%). Their serum thromboxane B2 (TxB2) levels were low, indicating inhibition of COX-1. They had significantly lower levels of ADAMTS13 antigen compared to patients with low RPR (517 vs 544 ng/mL, p = 0.001) and significantly lower ADAMTS13 activity (0.99 vs 1.04 IU/mL, p = 0.020). The differences were more pronounced when relating RPR to ratios of vWF/ADAMTS13 antigen and vWF/ADAMTS13 activity (p <0.001, both). We found an inverse correlation between vWF and ADAMTS13 antigen (r = -0.14, p < 0.001) and ADAMTS13 activity (r = -0.11, p < 0.001). No correlations between TxB2 and ADAMTS13 antigen or activity, were observed, implying that ADAMTS13 is not involved in TxB2 production. Patients who experienced endpoints (n = 73) had higher vWF level (113 vs 105%, p = 0.032) and vWF/ADAMTS13 antigen ratio (0.23 vs 0.20, p = 0.012) compared to patients without. When dichotomizing vWF/ADAMTS13 antigen at median level we observed that patients above median had higher risk for suffering endpoints, with an adjusted OR of 1.86 (95% CI 1.45, 2.82). Conclusion: These results indicate that ADAMTS13 is of importance for RPR, and that it in combination with vWF also is associated with clinical endpoints in stable CAD patients on aspirin. Trial registration: Clinicaltrials.gov NCT00222261. Registered 13.09.2005. Retrospectively registered. [ABSTRACT FROM AUTHOR]

The benefit of aspirin use after coronary artery bypass graft surgery has been well proven. However, the effect of preoperative aspirin use in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB) has not been evaluated sufficiently. To evaluate platelet function changes during OPCAB due to preoperative aspirin use, we conducted a randomized controlled trial using flow cytometry and the Multiplate® analyzer. Forty-eight patients scheduled for elective OPCAB were randomized to the aspirin continuation (100 mg/day until operative day) and discontinuation (4 days before the operative day) groups. Platelet function was measured using the platelet activation markers CD62P, CD63, and PAC-1 by flow cytometry, and platelet aggregation was measured using the Multiplate® analyzer, after the induction of anesthesia (baseline), at the end of the operation, and 24 and 48 h postoperatively. Findings of conventional coagulation assays, thromboelastography by ROTEM® assays, and postoperative bleeding—related clinical outcomes were compared between groups. No significant change in CD62P, CD63, or PAC-1 was observed at the end of the operation or 24 or 48 h postoperatively compared with baseline in either group. The area under the curve for arachidonic acid—stimulated platelet aggregation, measured by the Multiplate® analyzer, was significantly smaller in the aspirin continuation group (P < 0.01). However, chest tube drainage and intraoperative and postoperative transfusion requirements did not differ between groups. Our study showed that preoperative use of aspirin for OPCAB did not affect perioperative platelet activation, but it impaired platelet aggregation, which did not affect postoperative bleeding, by arachidonic acid. [ABSTRACT FROM AUTHOR]

Background Despite decades of clinical use, the pharmacokinetics and the effects of acetylsalicylic acid ( ASA) in critically ill patients remain ill-defined. We aimed to investigate the pharmacokinetics and the effects of different ASA formulations during critical illness. Design A cross-sectional study and a randomized, parallel-group trial were performed. Critically ill patients under chronic oral ASA treatment (100 mg enteric-coated) were screened for high 'on-treatment' platelet reactivity ( HTPR) according to arachidonic acid-induced whole-blood aggregometry. Thirty patients with HTPR were randomized to receive 100 mg ASA intravenously, 100 mg enteric-coated ASA bid (bis in die) or 81 mg chewable ASA ( n = 10 per group). Serum thromboxane B2 ( TXB2) levels, ASA and salicylic acid levels were quantified. Results Of 66 patients, 85% (95% confidence intervals 74-93%) had HTPR. Compared to baseline infusion of 100 mg, ASA significantly reduced platelet aggregation after 24 h to median 80% (Quartiles: 66-84%). Intake of 81 mg chewable ASA significantly reduced platelet aggregation to 75% (54-86%) after four hours, but increased it to 117% after 24 h (81-163%). Treatment with 100 mg enteric-coated ASA bid decreased platelet aggregation after 24 h to median 56% (52-113%). Baseline TXB2 levels were median 0·35 ng/mL (0·07-0·94). Infusion of ASA or intake of 100 mg ASA bid reduced TXB2 levels to 0·07-0·18 ng/mL after 24 h, respectively. Chewable ASA reduced TXB2 levels only transiently. Pharmacokinetic analysis revealed highly variable absorption patterns of oral ASA formulations. Conclusion There is a very high prevalence of HTPR in critically ill patients on peroral ASA therapy, caused by an incomplete suppression of TXB2 and/or by impaired absorption of ASA. [ABSTRACT FROM AUTHOR]

Background: The no-reflow (NR) phenomenon exists despite percutaneous coronary intervention (PCI), and is especially prevalent in diabetics. The causes(s) of NR are not fully elucidated, but may be associated with impaired residual platelet and inflammatory reactivity during dual-antiplatelet therapy. Objective: To assess the relationship between dual-antiplatelet therapy, NR and conventional biomarkers suggestive of platelet and inflammatory response in diabetics following ST-segment elevation myocardial infarction (STEMI) treated with PCI. Methods: Sixty diabetics with (n = 27) and without NR (n = 33) were prospectively enrolled. All patients were treated with clopidogrel and aspirin. Platelet and inflammatory biomarkers were assessed serially in the peripheral blood and right atrium before and after PCI and then at 24 h, 7 days and 30 days. Results: Arachidonic acid (AA)-induced platelet aggregation and the serum thromboxane B2 level before and after PCI (in the peripheral and right atrium blood) were significantly higher in the NR patients than in those with no NR. AA-induced aggregation >100 (AUC*min) before PCI predicted NR in diabetic patients with 96.2% sensitivity and 38.5% specificity (AUC 0.66; 95% CI 0.52-0.71; p = 0.029). There were no other correlations between NR and platelet reactivity (collagen, adenosine diphosphate, thrombin receptor agonist peptide-induced aggregation, vasodilator-stimulated phosphoprotein platelet reactivity index, soluble P-selectin, soluble CD40 ligand, platelet-derived growth factor AB and the level of platelet-monocyte aggregates) or between NR and inflammatory indices (i.e. high-sensitivity C-reactive protein, interleukin 6 and interleukin 10). Conclusion: An inadequate response to aspirin, but not to clopidogrel, may be associated with the occurrence of the NR phenomenon in diabetics with STEMI who have been treated with primary PCI. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aspirin is effective in the second prevention for stroke. However, its benefits and risk in the primary prevention are disputed. Based on current clinical observation, only part of the population could benefit from aspirin in the primary prevention. This article focuses on the evidence, mechanism, applicable people and risk assessment in the application of aspirin based on guidelines and important articles for the primary prevention of stroke. [ABSTRACT FROM AUTHOR]

Greater ex vivo platelet aggregation to agonists may identify individuals at risk of acute coronary syndromes (ACS). However, increased aggregation to a specific agonist may be masked by inherent variability in other activation pathways. In this study, we inhibited the cyclooxygenase-1 (COX1) pathway with 2-week aspirin therapy and measured residual aggregation to collagen and ADP to determine whether increased aggregation in a non-COX1 pathway is associated with incident ACS. We assessed ex vivo whole blood platelet aggregation in 1,699 healthy individuals with a family history of early-onset coronary artery disease followed for 6±1.2 years. Incident ACS events were observed in 22 subjects. Baseline aggregation was not associated with ACS. After COX1 pathway inhibition, collagen-induced aggregation was significantly greater in participants with ACS compared with those without (29.0 vs. 23.6 ohms, p < 0.001). In Cox proportional hazards models, this association remained significant after adjusting for traditional cardiovascular risk factors (HR = 1.10, 95%CI = 1.06-1.15; p < 0.001). In contrast, ADP-induced aggregation after COX1 inhibition was not associated with ACS. After COX1 pathway inhibition, subjects with greater collagen-induced platelet aggregation demonstrated a significant excess risk of incident ACS. These data suggest that platelet activation related to collagen may play an important role in the risk of ACS. [ABSTRACT FROM AUTHOR]

Background: The rate of cardiovascular diseases in developing countries is approximately 60% and it is still has an increasing trend. The clinical effectiveness of aspirin in preventing cardiovascular events has been well proven. Although aspirin is an effective and inexpensive drug, its consumption is not equally beneficial for all patients. Many factors can be affective on the efficacy of antiplatelet drugs such as aspirin. Methods: This study was carried out on 260 patients who had stable angina pectoris and coronary artery disease was approved by coronary angiography. Based on opium addiction, the patients were divided into two groups. Opium addiction was diagnosed base on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. The mid-stream morning urinary sample were collected for measuring the urinary 11-dehydroxy thromboxane B2 level (UTXB2). Urinary level of UTXB2 was considered as an aspirin resistance index. Findings: The mean age of patients was 57.3 ± 8.9; and 44.6% of them were females. The aspirin resistance rate was 41.5%. Significant difference in aspirin resistance was observed between the opium addicts and non-addicts. (51.5% vs. 31.5%) (P = 0.001). The effects of confounding variables such as diabetes, hypertension, and hyperlipidemia were eliminated by regression logistic multivariable analysis. Conclusion: The prevalence of aspirin resistance in patients with stable angina pectoris was 41.5%. The prevalence of aspirin resistance in patients with stable angina pectoris who had opium addiction was significantly higher them non-addicts. [ABSTRACT FROM AUTHOR]

The aim of this review is to introduce the concept of personalized medicine in secondary stroke prevention with antiplatelet medication. In the last years, many studies have been conducted regarding aspirin resistance and genotyping of clopidogrel metabolism. A review of the currently published data on this issue emphasizes the importance of focusing on the individualizing approach in antiplatelet therapy to achieve maximal therapeutic beneficial effect. However, many authors suggest that, before new information from ongoing trials become available, good clinical practice should dictate the use of low dose of aspirin that was shown to be effective in the prevention of stroke and death in patients with ischemic cerebrovascular disease, because higher doses do not have significantly better efficacy than lower doses in secondary stroke prevention, but lower-dose aspirin is associated with less side effects. On the other hand, many factors are associated with clopidogrel resistance, and recent genetic studies showed that the CYP2C19*2 genotype (loss-of-function allele) is related to poor metabolism of clopidogrel, but larger studies are needed to definitively confirm or rule out the clinical significance of this genetic effect. The aim of personalized approach in secondary stroke prevention is to take the most appropriate medicine in the right dose in accordance with the clinical condition of the patient and associated risk factors. [ABSTRACT FROM AUTHOR]

Once-daily, low-dose aspirin is a cornerstone in the prophylaxis and treatment of cardiovascular diseases. Aspirin 'resistance' still lacks definition, a standardized reference assay, underlying mechanisms, clinical impact or efficacy of alternative antiplatelet drugs. Aspirin response in several studies has been measured by different platelet function tests, not always reflecting aspirin pharmacodynamics, thus generating significantly heterogeneous results. The EMA indicated serum thromboxane B2 as the only valid surrogate assay to study different aspirin formulations. Rather than resistance, recent studies focused on sources of intra- and interindividual variability in response to aspirin, based on pharmacokinetic and/or pharmacodynamic mechanisms. Drug interactions, diabetes, conditions of increased platelet output, obesity and aging can potentially increase the variability of aspirin response. Preliminary studies testing different aspirin regimens showed that twice-daily low doses were more effective than oncedaily higher aspirin doses on surrogate end points of platelet inhibition. Large studies are needed to test new disease-tailored, low-dose aspirin regimens. [ABSTRACT FROM AUTHOR]

Copyright of Polish Surgery / Chirurgia Polska is the property of VM Medica-VM Group (Via Medica) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

SUMMARY Cardiovascular diseases are the most common cause of mortality and morbidity in Western countries, accounting for more than 40% of total mortality. An optimal pharmacological management in these patients is of major importance and antiplatelet agents remain the cornerstone of acute coronary syndrome (ACS) therapy at hospital admission and during percutaneous coronary interventions (PCI). The recently described poor biological responses to aspirin and clopidogrel have been source of major concern, especially in era of drug eluting stent implantation. Indeed, insufficient platelet inhibition at the time of PCI has been consistently associated with an increased risk of complications and recurrence of ischemic events. Despite the lack of uniformly accepted definitions of aspirin and clopidogrel poor response, we sought to describe the current evidence and gaps in knowledge. While trials on the potential benefit of an increased antiplatelet maintenance dose after PCI have shown only marginal benefits, the strengthening of the initial antiplatelet regimens by additional loading doses of clopidogrel, by the administration of glycoprotein IIb/IIIa receptor inhibitors or phosphodiesterase inhibitors might further improve outcomes during ACS and PCI in patients with poor responsiveness to conventional dual antiplatelet therapy. Overall, tailoring the antiplatelet treatment on the basis of the individual biological response improves the short-term outcome after PCI. New and more potent antiplatelet drugs may overcome the clinical consequences of the poor response to antiplatelet agents. [ABSTRACT FROM AUTHOR]

Objectives: Pharmacologic evidence suggests adequate antiplatelet activity in diabetic patients requires >100 mg aspirin daily, yet recent trials have used ≤100 mg daily. This meta-analysis explored the relationship between aspirin dose and prevention of cardiovascular events. Data Sources: Six electronic databases were searched using database-appropriate terms for aspirin, diabetes, and comparative study from inception until February 2010. Review Methods: Randomized controlled trials and cohort studies comparing aspirin to no antiplatelet therapy were included if they reported cardiovascular events as pre-specified outcomes, aspirin dose, and number of diabetic patients. Studies were stratified by daily aspirin dose (≤100 mg; 101-325 mg; >325 mg) and pooled risk ratios (RR) were calculated using random effects models. All-cause mortality was the primary outcome of interest. Cardiovascular-related mortality, myocardial infarction, and stroke were secondary outcomes. Results: Data for diabetic patients were available from 21 studies ( n = 17,522). Overall, 1,172 (15.4%) of 7,592 aspirin users and 1,520 (18.4%) of 8,269 controls died ( p = 0.31). The pooled RRs were 0.89 (95% CI: 0.72-1.10; p = 0.27) from 13 studies using ≤100 mg (I = 64%); 0.89 (95% CI: 0.61-1.30; p = 0.55) from four studies using 101-325 mg (I = 83%); and 0.96 (95% CI: 0.85-1.08; p = 0.50) from eight studies using >325 mg (I = 0%). Aspirin use was associated with a significantly lower risk of mortality (RR: 0.82; 95% CI: 0.69-0.98; p = 0.03) in 13 secondary prevention studies (I = 27%), whereas aspirin use in seven primary prevention studies (I = 0%) was not (RR: 1.01; 95% CI 0.85-1.19; p = 0.94). A substantial amount of heterogeneity was observed amongst studies in all outcomes. Although inclusion of cohort studies was a major source of heterogeneity, stratification by study design did not reveal a significant dose-response relationship. Conclusions /Interpretation: This summary of available data does not support an aspirin dose-response effect for prevention of cardiovascular events in diabetic patients. However, the systematic review identified an important gap in randomized controlled trial evidence for using 101-325 mg aspirin daily in diabetes. [ABSTRACT FROM AUTHOR]

Previous clinical studies have shown heterogeneity in individual patient responses to antiplatelet therapy and high residual platelet reactivity is associated with increased risk of adverse clinical events. Monitoring response to antiplatelet therapy and tailoring treatment accordingly is currently not recommended in routine clinical practice largely due to the lack of a standardized definition of antiplatelet therapy hyporesponse and the need for a widely accepted point-of-care platelet function test that can be reliably utilized in frontline clinical practice. Recent data have shown that titrating the dose of clopidogrel in patients undergoing percutaneous coronary intervention significantly reduces the incidence of major adverse cardiovascular events and large-scale clinical trials are currently underway to investigate whether individually tailored treatment based on results of platelet function testing leads to improved clinical outcome. Furthermore, genetic testing has demonstrated a link between CYP2C19 genetic polymorphisms, altered clopidogrel metabolite concentrations and adverse clinical events. Clinical studies are currently underway to investigate the potential clinical benefit associated with genotype-guided tailoring of antiplatelet therapy. With the advent of newer, more potent antiplatelet agents and their associated increased bleeding risks, it will become imperative in the future to select the most appropriate, safe and effective drug. [ABSTRACT FROM AUTHOR]

Acetyl salicylic acid (ASA) and clopidogrel are extensively used in the prevention of cardiovascular disease. However, the responsiveness to ASA treatment may vary among individuals. This study was conducted to investigate the profile and prevalence of ASA resistance in cardiac patients. From August 2007 to August 2008, a total of 282 cardiac patients were enrolled. Two study groups were identified: patients taking 100 mg ASA daily but without clopidogrel, and patients taking both 100 mg ASA and 75 mg clopidogrel daily. Platelet function was determined with the Multiplate analyzer to determine platelet responsiveness. Salicylate blood level was measured for all patients on ASA. Seventy-three patients (26%) were determined to be nonresponsive to ASA, and 45 patients (16%) were partially responsive, whereas 164 patients (58.2%) were responsive to ASA. Myocardial infarction and coronary obstruction were both strongly associated with ASA nonresponsiveness ( p < 0.001). ASA resistance occurred more in female patients ( p = 0.002). The salicylate blood level was found to be low in ASA-resistant patients (35.33 ± 50.22 mg/l) and higher in sensitive patients (54.26 ± 18.7 mg/l; p < 0.001). Quantitative assessment of platelet functions is predictive of ASA treatment failure in individual patients. Dual antiplatelet treatment with clopidogrel and ASA was found to have greater inhibitory effects on platelet aggregation than either agent alone. Non-adherence may be a significant mediator of poor outcome. [ABSTRACT FROM AUTHOR]

Sixty-six patients with a history of ischemic events (myocardial infarction, unstable angina, or stroke) on chronic aspirin therapy were studied by different platelet function tests: 37 patients had suffered a recurrent event while on aspirin and 29 were without recurrences. Based on results from light transmission aggregometry (LTA) induced by arachidonic acid (AA) and serum TxB2 both COX-1-dependent methods, only one patient could be identified as aspirin ''resistant''. However, when methods only partially-dependent on platelet COX-1 activity were considered, the prevalence of aspirin non-responders ranged, according to the different tests, from 0 to 52%%. No difference was observed between patients with recurrences and those without. Among patients with recurrent events, those with an incomplete inhibition of platelet function, as assessed by the PFA-100, had significantly higher residual serum TxB2 (2.4 ±± 2.4 ng/mL vs 0.4 ±± 0.1 ng/mL, p == 0.03), residual LTA-AA (9.2 ±± 10.6%% vs 2.0 ±± 1.6%%, p == 0.008), LTA-Coll (49.3 ±± 14.6%% vs 10.2 ±± 8.3%%, p == 0.007) and LTA-ADP (50.9 ±± 16.2%% vs 34.3 ±± 11.0%%, p == 0.04). In conclusion, laboratory tests solely exploring the AA-mediated pathway of platelet function, while being the most appropriate to detect the effect of aspirin on its pharmacologic target (platelet COX-1), may fail to reveal the functional interactions between minimal residual TxA2 and additional stimuli or primers potentially leading to aspirin-insensitive platelet aggregation. High residual platelet response in platelet function tests only partially dependent on COX-1 may reveal a condition of persistent platelet reactivity in a subset of aspirin-treated patients characterizing them as a subgroup at higher vascular risk. [ABSTRACT FROM AUTHOR]

Point-of-care platelet monitoring is increasingly used in cardiac patients treated with antiplatelet agents. The validity of a new assay needs to be evaluated not only for reproducible data in clinical samples, but also for other pre-analytical conditions that may influence measurements. The aim of this study was to evaluate the influence of a pneumatic tube system (PTS) for specimen transport on impedance platelet aggregometry. We evaluated 50 consecutive patients scheduled for coronary artery bypass surgery under oral therapy with 100 mg/d acetylsalicylic acid (aspirin). In each patient, three blood samples for platelet function analysis were taken before induction of anesthesia. The first sample was measured in the operating room (OR) area and designated as the reference value. The second sample was again measured by the same operator in the OR area using a random PTS transport. The third sample was sent to the central laboratory by PTS where it was measured by a local technician. Platelet function was assessed in whole blood by impedance aggregometry with a Multiplate™ analyzer using thrombin-related activation peptide (TRAP test) and arachidonic acid (ASPI test) (Dynabite GmbH, Munich, Germany). Mean ± SD for TRAP test was 1009 ± 196 in the reference measurement. Bias ± 95% limit of agreement between the reference measurement and a second measurement for TRAP test were 126 ± 284 (n = 25) for untransported and 181 ± 316 (n = 25) for PTS transported samples. In the reference measurements, 48/50 (96%) of TRAP values were within the normal range. After PTS transport, 35/50 (70%) of TRAP measurements in the central laboratory were within the normal range (p < 0.001). Mean ± SD for ASPI test was 175 ± 137. Bias ± 95% limit of agreement for ASPI test were 12 ± 109 (n = 25) for untransported and 68 ± 250 (n = 25) for PTS transported samples. In the reference measurements, 7/50 (14%) ASPI values were above the cut-off level and defined as reduced aspirin responsiveness. After PTS transport, only 1/50 (2%) of the patients showed reduced aspirin responsiveness in the central laboratory measurements (p = 0.031). In conclusion, PTS transport had a significant influence on platelet function testing by the Multiplate™ analyzer. Significantly fewer test results indicated normal platelet function in TRAP test and reduced aspirin responsiveness in ASPI test after PTS transport. Therefore, clinical decisions regarding platelet function and aspirin responsiveness should not be based on blood specimens transported by a PTS system. [ABSTRACT FROM AUTHOR]

The role of antithrombotic drugs in the prevention of cerebral infarction is well established: antiplatelet drugs, at present mostly aspirin, clopidogrel, and aspirin + extended-release dipyridamole, decrease the relative risk of cerebral infarction, myocardial infarction and vascular death by 25% in patients with a cerebral ischemic event due to large- or small-artery disease of the brain. In primary prevention, aspirin decreases stroke risk by 19% in women but not in men. In patients with nonvalvular atrial fibrillation (NVAF), aspirin decreases the risk of ischemic stroke by 20%. Oral anticoagulants, at present only vitamin K antagonists, decrease the risk of cerebral infarction in NVAF by 65–70% compared with placebo and by 40% compared with aspirin. Oral anticoagulants are as effective as aspirin in arterial diseases of the brain, but induce more hemorrhages and are less convenient. Studies are ongoing with new antiplatelet drugs and new anticoagulants which might modify the present state of the art. Studies are also needed to evaluate the benefit/risk ratio of the combination of anticoagulants and antiplatelet drugs in aged subjects with both NVAF and arterial diseases of the brain. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aspirin and clopidogrel are the most commonly used antiplatelet agents in patients with coronary artery disease. The existence of resistance to these agents has been a controversial issue and new drugs are being developed to overcome this problem. Laboratory tests, which can identify resistance and correlate this with clinical outcome, are being studied in order to identify patients at risk of future thrombotic events. We discuss the evidence for the existence of antiplatelet resistance--both in the laboratory and in the clinical setting. So far, platelet aggregometry has been considered the gold standard test, but is very operator dependant, time consuming, and has shown little correlation with other available tests of antiplatelet resistance. We discuss the available tests of platelet function, their limitations, and evidence for their use. A simple, rapid, near-patient test, which is affordable and useful in the clinical (not just laboratory) setting, could allow risk stratification of patients and individualization of antiplatelet medication to improve outcome. [ABSTRACT FROM AUTHOR]

Aspirin is one of the 'cornerstone' drugs in our current management of cardiovascular disorders. However, despite the prescription of aspirin recurrent vascular events still occur in 10-20% of patients. These, data together with the observations of diminished antiaggregatory response to aspirin in some subjects have provided the basis of the current debate on the existence of so-called "aspirin resistance". Unfortunately, many of the tests employed to define 'aspirin resistance' lack sufficient sensitivity, specificity, and reproducibility. The prevalence of 'aspirin resistance' as defined by each test varies widely, and furthermore, the value of a single point estimate measure of aspirin resistance is questionable. The rate of 'aspirin resistance' is law if patients observed to ingest aspirin, with large proportion of patients to be pseudo-'aspirin resistant', due to non-compliance. What are the implications for clinical practice? Possible non-adherence to aspirin prescription should also be carefully considered before changing to higher aspirin doses, other antiplatelet drugs (e.g. clopidogrel) or even combination antiplatelet drug therapy. Given the multifactorial nature of atherothrombotic disease, it is not surprising that only about 25% of all cardiovascular complications can usually be prevented by any single medication. We would advocate against routine testing of platelet sensitivity to aspirin (as an attempt to look for 'aspirin resistance') but rather, to highlight the importance of clinicians and public attention to the problem of treatment non-compliance. [ABSTRACT FROM AUTHOR]

This article presents a clinical review of aspirin therapy for the prevention of cardiovascular disease. The object was to review the mechanism of action of aspirin and the clinical literature for relationships among aspirin dosage, efficacy and safety. The conclusion of the authors is that currently available clinical data does not support the routine, long-term use of aspirin dosages greater than 75 to 81 md/d in the setting of cardiovascular disease prevention. Higher dosages do not prevent events better but are associated with increased risk of gastrointestinal bleeding.