Mg Of Aspirin Research Articles

Does aspirin use prevent acute coronary syndrome in patients with pneumonia

The aim of this study was to test the hypothesis that aspirin would reduce the risk for acute coronary syndromes (ACSs) in patients with pneumonia. Pooled data suggest that pneumonia may trigger an ACS as a result of inflammatory reactions and the prothrombotic changes in patients with pneumonia. Hypothetically considering its antiaggregating and anti-inflammatory effects, aspirin might also be beneficial for the primary prevention of ACS in patients with pneumonia. One hundred and eighty-five patients with pneumonia who had more than one risk factor for cardiovascular disease were randomized to an aspirin group (n=91) or a control group (n=94). The patients in the aspirin group received 300 mg of aspirin daily for 1 month. ECGs were recorded on admission and 48 h and 30 days after admission to assess silent ischemia. The level of high-sensitivity cardiac troponin T was measured on admission and 48 h after admission. The primary endpoint was the development of ACS within 1 month. The secondary endpoints included cardiovascular death and death from any cause within 1 month. The χ-test showed that the rates of ACS at 1 month were 1.1% (n=1) in the aspirin group and 10.6% (n=10) in the control group (relative risk, 0.103; 95% confidence interval 0.005-0.746; P=0.015). Aspirin therapy was associated with a 9% absolute reduction in the risk for ACS. There was no significant decrease in the risk of death from any cause (P=0.151), but the aspirin group had a decreased risk of cardiovascular death (risk reduction: 0.04, P=0.044). This randomized open-label study shows that acetyl salicylic acid is beneficial in the reduction of ACS and cardiovascular mortality among patients with pneumonia.

The effect of long‐term aspirin intake on the outcome of non‐surgical periodontal therapy in smokers: a double‐blind, randomized pilot study

The objective of this parallel, double-blind, randomized pilot study was to determine the effect of a daily dose of 325mg of aspirin (ASA) on the clinical outcomes of scaling and root planing in a selected group of adult smokers. The response to periodontal therapy is inferior among smokers compared to non-smokers. Long-term intake of ASA has been shown to exert a positive impact on reducing both the prevalence and severity of periodontitis, among high-risk groups of subjects such as heavy smokers and diabetics. It is reasonable to assume that systemic administration of ASA in conjunction with reduction of the bacterial load by scaling and root planing may improve and prolong the benefits of periodontal therapy. To date, only few prospective interventional clinical studies have specifically addressed the periodontal needs of smokers. The study includes 24 smokers. The following clinical parameters were measured preoperatively and at 3, 6, 9 and 12mo postoperatively: (i) gingival index; (ii) plaque index; (iii) probing depth; (iii) probing attachment level; (iv) gingival recession; and (v) bleeding scores. Study subjects received scaling and root planing over several visits and were randomly assigned into two equal groups; a control group (C), which received a placebo and a test group (T), which took a daily dose of 325mg ASA. No additional therapy was provided over the 1year observation period. There were more statistically significant differences (p<0.05; one- tailed) between pretest and posttest scores in the T group than in the C group. Mean percent increase in sites with probing depth 1-3mm (T: 8.78; C: 7.21); mean percent reduction in sites with probing depth 4-6mm (T: -7.25; C: -5.09 not statistically significant, NS); mean percent reduction in sites with probing depth ≥7mm (T: -1.42; C: -02.09); mean percent reduction in sites with probing attachment level 3-4mm (T: -3.63; C: 0.48NS); mean percent reduction in sites with bleeding on probing (T: -12.37; C: -2.59NS) (p<0.05, NS). Daily intake of 325mg of ASA following scaling and root planing improved treatment outcomes in smokers, without an increase in gingival bleeding tendency. ASA promoted a higher incidence of shallow pockets and more gain in attachment level.

Aspirin and recurrent venous thromboembolism

While there is conclusive evidence that aspirin plays a role in reducing the risk of clinically relevant venous thromboembolism (VTE) arising in a number of surgical and non-surgical situations at risk, little is known of the potential of aspirin for the long/term prevention of recurrent VTE. In two recent multicentre, double-blind studies (WARFASA and ASPIRE), the efficacy and safety of a low dose of aspirin (100 mg per day) were assessed in patients with unprovoked VTE who had completed an initial period of conventional treatment with vitamin K antagonists. The two studies used identical aspirin regimens and had similar enrollment criteria and outcome measures. When data from these two trials were pooled, there was a 32% reduction in the rate of recurrence of VTE (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.90) and a 34% reduction in the rate of major vascular events (HR, 0.66; 95% CI, 0.51-0.86). Moreover, these benefits were achieved with a low risk of bleeding. As patients with previous symptomatic atherosclerosis were not enrolled in these two studies, whether these results apply also to this category of patients is uncertain. We recently had the opportunity to review the clinical charts of 1919 consecutive patients presented with a first episode of VTE, which was either unprovoked or triggered by transient risk factors, and were followed up for an average period of four years after discontinuing anticoagulation. The rate of recurrent VTE in the 256 patients with a history of symptomatic atherosclerosis who had been given 80-160 mg of aspirin once daily (17.2%) did not differ from that (19.9%) observed in those without atherosclerosis who were left without any antithrombotic treatments. The implication of this observation is that whenever patients with symptomatic atherosclerosis are deemed to require long-term protection against recurrent VTE, they are unlikely to benefit from (resuming) aspirin. Conversely, aspirin in low doses offers an appealing, safe and highly cost-effective option for the long-term prevention of recurrent events in patients with unprovoked VTE who are free from symptomatic atherosclerotic lesions.

Effect of Low-Dose Aspirin on Functional Outcome From Cerebral Vascular Events in Women

Although aspirin is effective in prevention of stroke, fewer studies have examined the impact of aspirin on stroke morbidity. The Women's Health Study is a completed randomized, placebo-controlled trial designed to test the effect of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer, which enrolled 39 876 women. We used multinomial logistic regression to evaluate the relationship between randomized aspirin assignment and functional outcomes from stroke. Possible functional outcomes were neither stroke nor transient ischemic attack (TIA), modified Rankin scale (mRS) score 0 to 1, 2 to 3, and 4 to 6. After a mean of 9.9 years of follow-up, 460 confirmed strokes (366 ischemic, 90 hemorrhagic, and 4 unknown type) and 405 confirmed TIAs occurred. With regard to total and ischemic stroke, women who were randomized to aspirin had a nonsignificant decrease in risk of any outcome compared to women not randomized to aspirin. This decrease in risk only reached statistical significance for those experiencing TIA compared to participants without stroke or TIA (odds ratio=0.77; 95% confidence interval, 0.63-0.94). For hemorrhagic stroke, a nonsignificant increase in the risk of achieving an mRS score 2 to 3 or 4 to 6 compared with no stroke or TIA was observed for the women randomized to aspirin compared to those randomized to placebo. Results from this large randomized clinical trial provide evidence that 100 mg of aspirin every other day may reduce the risk of ischemic cerebral vascular events but does not have differential effects on functional outcomes from stroke.

020: Impact of anti-platelets dose fractionation on platelet inhibition in type 2 diabetes mellitus

The hypothesis of the study was that increased drug administration frequency [twice daily versus once daily] may provide more effective platelet inhibition in patients with type 2 diabetes mellitus. Twenty patients with type 2 diabetes mellitus with stable coronary artery disease were prospectively recruited. All the patients received once daily 150 mg of aspirin and clopidogrel for two weeks. Then patients were switched to aspirin and clopidogrel 75 mg twice daily for two weeks. Pharmacodynamic assessment was performed by VerifyNow system accumetrics at fifteen and thirty days. There was no difference between the antiplatelet effect produced by 150 mg of aspirin given once daily and 75 mg of aspirin given twice daily. A twice-daily dose of 75 mg of clopidogrel is associated with significantly more effective platelet inhibition on the residual assay: PRU=38.2% once daily vs 53.8% twice daily (p= 0.001) and PRU=187 once daily vs 147 twice daily (p=0.005). Increasing the frequency of clopidogrel administration to twice daily in patients with type 2 diabetes mellitus is significantly associated with more effective platelet inhibition. But our data do not support a twice-daily dose of aspirin to improve platelet response.

Letter to the Editor Coronary artery dissection, traumatic liver and spleen injury after cardiopulmonary resuscitation – a and review of the literature

Letter to the Editor Coronary artery dissection, traumatic liver and spleen injury after cardiopulmonary resuscitation – a and review of the literature

Immediate hyphema after intravitreal injections of ranibizumab.

To report two cases of immediate hyphema formation after the intravitreal injection of ranibizumab. Retrospective case reports. A patient with choroidal neovascularization caused by exudative age-related macular degeneration and a patient with cystoid macular edema caused by branch retinal vein occlusion underwent an intravitreal injection of 0.5 mg/0.05 mL of ranibizumab. The development of hyphema was seen immediately after the intravitreal injection in both cases. One patient was pseudophakic, taking 325 mg of aspirin daily. The other patient was phakic without any anticoagulation history. To the best of our knowledge, this is the third report of the development of hyphema associated with intravitreal injections.

Patency of infarct-related artery and platelet reactivity in patients with ST-segment elevation myocardial infarction

BackgroundOutcome in ST-segment elevation myocardial infarction (STEMI) is affected by patency of the infarct-related artery (IRA) on the initial angiogram. There is a controversy if preloading with antiplatelet drugs affects initial IRA patency in case of shortening transportation time for primary percutaneous coronary intervention (PCI). The aim of the study was to assess the relation between IRA patency and platelet reactivity on admission after preloading with aspirin and clopidogrel within 2h to primary PCI. MethodsThe study included 49 subjects who received 600mg of clopidogrel and 300mg of aspirin and underwent primary PCI within 120min from loading. Platelet reactivity testing was performed on admission with means of impedance aggregometry after induction with arachidonic acid (ASPItest) and adenosine diphosphate with prostaglandin E1 (ADPtest HS) to assess response to aspirin and clopidogrel, respectively. IRA patency was defined as TIMI flow 2 or 3 on the initial angiogram. ResultsPatent IRA on the initial angiogram was found in 20 patients (41%). Median time between preloading with antiplatelet drugs and primary PCI was 64min (IQR 59–84min). Patients who received clopidogrel earlier than 84min before PCI (fourth quartile) had more suppressed platelet reactivity than patients in the first quartile (<59min) as measured with ADPtest HS (p=0.04). Nevertheless, there was no difference in platelet reactivity between patients with and without IRA patency on the initial angiogram. ConclusionsIn patients preloaded with aspirin and clopidogrel within 2h to primary PCI, there was no association between the magnitude of platelet inhibition and IRA patency at the time of the initial coronary angiography.

Toward a guided approach to platelet activation in diabetes

Diabetes is associated with substantially poorer cardiovascular outcomes. Furthermore, people with diabetes are at greatly increased risk of not responding to standard antiplatelet therapy for acute coronary syndromes, leading to higher mortality and stent thrombosis [1]. Poor glucose control likely contributes to these cardiovascular events through changes in platelet membrane fluidity and signalling, increased production of platelets leading to a greater fraction of younger and more reactive platelets not yet exposed to antiplatelet therapy, and increased triggering of platelet activation arising from an underlying thromboinflammatory milieu [2]. While patients with higher thrombotic risk may be prospectively identified through laboratory identification of elevated blood glucose or HbA1c [3], the approach to treatment for diabetic platelet hyper-responsiveness remains unclear. Options such as increasing frequency of antiplatelet therapy, additional and more aggressive antiplatelet therapy or more intensive glucose control have been suggested (Fig. 1). However, the data to support these are limited and, particularly where more aggressive antiplatelet therapy is proposed, must be measured against the potential for increased bleeding risk in patients with hyperglycemia. In patients with type-2 diabetes, Capodanno et al. [4] demonstrated enhanced inhibition of platelet function when patients took 81 mg of aspirin twice per day compared with 81 mg daily. Spectre et al. [5] showed greater inhibition of platelet function with 75 mg twice per day when compared to 75 mg daily in patients with type-2 diabetes and vascular complications. In a recent study Rocca et al. [6] showed that increasing frequency of dose better attenuated platelet activation over 24 h in both diabetic and non-diabetic patients. Therefore increasing the frequency of antiplatelet therapy dosing represents an appealing strategy in patients with diabetes and poor glycemic control. However, the clinical effectiveness of this approach on cardiovascular outcome, as well as the net benefit against increased bleeding risk remains to be investigated. Similarly, the addition of more aggressive antiplatelet therapy, such as newer ADP receptor antagonists with greater potency and bioavailability, or emerging thrombin receptor antagonists have been suggested [2]. The use of these must be weighed against the potentially increased risk of bleeding. While altering antiplatelet therapy strategies in patients with diabetes and poor glycemic control is an appealing avenue for further clinical investigation, a potential alternative or complimentary approach might be to achieve improved glycemic control in order to attenuate platelet activation. Several studies have assessed the ability of infused insulin in patients with diabetes to attenuate platelet function and improve cardiovascular outcome in acute coronary syndromes [7]. While evidence of improvement in cardiovascular outcome is variable, intensive treatment with insulin in patients with diabetes may attenuate platelet activation relative to conventional approaches to glycemic control [8]. In this issue of the Journal of Thrombosis and Thrombolysis, Vivas et al. [9] explore whether tight glycemic control with insulin infusion attenuates platelet reactivity in patients with an acute coronary syndrome and hyperglycemia at admission. In a post hoc analysis of the prospective, randomized, open-label CHIPs study, 67 patients with poor glycemic control (as measured by HbA1c [ 6.5 %) were M. D. Linden (&) Centre for Microscopy, Characterisation and Analysis, M510, University of Western Australia, 35 Stirling Highway, Nedlands, WA 6009, Australia e-mail: matthew.linden@uwa.edu.au

Safety of Peri-Operative Low-Dose Aspirin as a Part of Multimodal Venous Thromboembolic Prophylaxis for Total Knee and Hip Arthoplasty

To examine whether it is safe to continue low-dose (100 mg/day) aspirin perioperatively as a part of standard multimodal venous thromboembolic prophylaxis for total hip arthroplasty (THA) or total knee arthroplasty (TKA). 79 women and 60 men aged 52 to 91 years who underwent THA (n=50) or TKA (n=89) were prospectively studied. Preoperatively, 63 of the patients were on 100 mg of aspirin every morning for various medical reasons and continued in the perioperative period, except for the operation day. The remaining 76 patients were controls. Pre- and post-operative haemoglobin levels, postoperative blood drainage, and the amount of reinfused drained blood were recorded. Intra-operative blood loss and operative times were recorded for THA only. These parameters for the aspirin and control groups were compared. All the parameters, namely blood loss (intraoperative and postoperative), operative time, surgical wound healing, and drop in the haemoglobin level (determined on day 3) did not differ significantly between the 2 groups. It is safe to continue low-dose (100 mg/day) aspirin in the perioperative period as a part of multimodal prophylaxis against deep vein thrombosis.

Pharmacodynamics of Platelet Inhibition with Aspirin: Feasibility for Detection of Suboptimal Platelet Inhibition

AbstractAbstract 4361 Introduction:Patients with diabetes mellitus and or metabolic syndrome may or may not be maximally protected from future vascular events with aspirin. To be maximally protected at least 90% of platelets should be inhibited by aspirin (aspirinated). Since platelet acetylation by aspirin is limited to the first 30 minutes after ingestion, in conditions associated with increased platelet production the percentage of aspirinated platelets could be diluted to less than 90% with the usual daily dosing. We studied the pharmacodynamics of aspirin inhibition of platelets to evaluate the feasibility of developing a metric that would detect suboptimal aspirin inhibition of platelets. Methods:The slope of the platelet prostaglandin agonist (PPA) stimulated light aggregometry curve was used to gage the degree of platelet inhibition with aspirin.(Schwartz J. Lab Clin Med 2002; 139:227) Seven normal subjects were studied. After observed ingestion of 325mg of aspirin, the degree of platelet inhibition was studied at the following post aspirin time points; 0, 8hrs, 24hrs and 48hrs. Ex-vivo dilution curves were constructed using time 0 as 100% non-aspirinated and 1hr post aspirin as 100% aspirinated under the assumption that over 24hrs 10% of platelets are newly formed and non-aspirinated. Statistical evaluations were performed for each subject studied using both within subject comparisons and considering the group as a whole, between-subject comparisons.Results: Within group comparisons:A linear regression analysis comparing the in-vivo PPA aggregometry slopes with the PPA slopes obtained via ex-vivo dilutions demonstrated that the ex-vivo dilution curves for a particular subject reliably predicted the degree of aspirin inhibition observed in-vivo for that subject at the following time points with their corresponding percentages of aspirinated platelets; 8hrs (97% aspirinated) 24hrs (90% aspirinated) and 48hrs (80% aspirinated) (r2=0.6, p< 0.001). In addition, a direct in group comparison showed no differences between the in-vivo PPA slopes and those obtained with ex-vivo dilutions with 8 hr. and 48 hr. time points (p=0.16 and p=0.31, respectively), but a difference was observed at the 24 hr. time point (p=0.02). Entire group comparisons: Platelet inhibition with aspirin was highly variable among subjects. When analyzed as a group, the ex-vivo dilution curves were not predictive of the slopes obtained in-vivo. The PPA slopes observed in-vivo were significantly different from those obtained from the ex-vivo dilution curves at all of the time points (p<0.05). Conclusions:1. In normal subjects the ex-vivo dilution curve for a particular subject reliably predicts the degree of platelet inhibition observed in-vivo for that subject. 2. The variation in aspirin inhibition among subjects is large and suggests that the development of a metric to detect suboptimal platelet inhibition with aspirin is only possible if the individual subjects serve as their own control. Disclosures:No relevant conflicts of interest to declare.

Abstract PR-03: Aspirin mediated downregulation of Warburg kinase AKT1 in patients with Barrett's esophagus: Implications in neoplastic transformation

Abstract Background: In patients with Barrett's esophagus, chronic reflux injury and inflammation are associated with esophageal adenocarcinoma, one of the most rapidly increasing lethal cancers. Epidemiological and preclinical studies support decreased risk of esophageal adenocarcinoma with NSAID use. Gastroesophageal refluxate contents can promote carcinogenesis in Barrett's metaplasia by activating AKT, which up regulates COX-2 expression and prostaglandin biosynthesis. We recently noted that neoplastic transformation in Barrett's esophagus is associated with increased AKT expression, particularly isoform AKT1. The AIM of this study is to investigate the effect of NSAID (Aspirin) use in patients with Barrett's esophagus on AKT1 expression using frozen tissue from the randomized, phase II trial of aspirin and esomeprazole for esophageal cancer chemoprevention in Barrett's esophagus patients and to assess the functional consequences of AKT1 expression in-vitro. Methods and Results: In a subset of patients (12 of 120 patients) with Barrett's esophagus who were randomized to placebo, lower dose (81 mg) or higher dose (325 mg) Aspirin for 4 weeks, both PCR and Western blot revealed marked reduction in AKT1 expression in patients who received 325 mg of Aspirin daily compared to patients who received placebo. Our in-vitro experiments support that AKT1 expression is functionally relevant to the process of carcinogenesis in Barrett's epithelial cells. Using adenovirus to induce AKT1 expression, we show that increased AKT1 expression increases Barrett's epithelial cell growth, facilitates RAS-mediated transformation of pre-neoplastic epithelial cells and promotes colony formation. Since AKT1 is known as Warburg kinase and regulates cellular glucose uptake to support aerobic glycolysis during growth de-regulation and neoplasia, we examined the uptake of fluorescent deoxyglucose analog (2-NBDG) in Barrett's epithelial cells transduced with AKT1 adenovirus. At 48 hrs, compared to control, AKT1 overexpression resulted in increased glucose uptake both by metaplastic and neoplastic Barrett's epithelial cells. Transcriptional repression of AKT1 abrogated the 2-NBDG uptake by these cells. Finally, we did pathway specific qPCRs and noted that use of Aspirin is associated with altered expression of chromatin remodelers that could down-regulate AKT1 expression. Conclusion: Collectively, our results demonstrate that Aspirin mediated down-regulation of Warburg kinase AKT1 in patients with Barrett?s esophagus is a novel mechanism for the regulation of Barrett?s epithelial cell growth. The in-depth characterization of molecular mechanisms is currently underway. This abstract is also presented as Poster A82. Citation Format: Navtej S. Buttar, Gary W. Falk, Cathrine J. DeMars, Sonia Chowdhury, Ahmed Elebiary, Anamay Sharma, Sidhartha Chaudhry, Nathan R. Foster, Katie L. Allen Ziegler, Yvonne Romero, Norman E. Marcon, Thomas Schnell, Douglas A. Corley, Prateek Sharma, Marcia R. Cruz-Correa, Chin Hur, David E. Fleischer, Amitabh Chak, Kenneth R. DeVault, David S. Weinberg, Gary Della’Zanna, Ellen Richmond, Thomas C. Smyrk, Sumithra Mandrekar, Paul J. Limburg. Aspirin mediated downregulation of Warburg kinase AKT1 in patients with Barrett's esophagus: Implications in neoplastic transformation. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr PR-03.

Cerebral Microembolization After Bioprosthetic Aortic Valve Replacement

No human physiological data exists on whether aspirin only is as effective as warfarin plus aspirin in preventing cerebral microembolization in the early postoperative period after bioprosthetic aortic valve replacement (bAVR). We prospectively enrolled 56 patients who had no other indication for oral anticoagulation, who underwent bAVR and received, in an open-label fashion, either daily warfarin (for INR 2.0-3.0) plus 81 mg of aspirin (n=28) or 325 mg of aspirin only (n=28). Cerebral microembolization was quantified at 4 hours (baseline) and at 1 month postoperatively, by recording 1-hour bilateral middle cerebral artery (MCA) microembolic signals (MES). Platelet-function analysis (PFA) of closure times (CT) on collagen was also used as a marker of platelet-dependent activation. Follow-up to 1 year was complete. Preoperative demographics and baseline platelet function were equivalent in both groups. There was no mortality, stroke, or transient ischemic attack at 1 year in either group. No significant differences were found in the proportion of patients with MES among those receiving warfarin plus aspirin versus aspirin only, at baseline (68% versus 82%, respectively; P=0.4) and at 1 month (46% versus 43%; P=1.0) after bAVR. The total MES and PFA were also equivalent between groups, at baseline and follow-up. Early after bAVR, the effects of these 2 antithrombotic regimens on cerebral microembolization and platelet function are equivalent. These data bring new mechanistic support to the premise that aspirin only may safely be used early after bAVR in patients who have no other indication for oral anticoagulation.

Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke

BackgroundLacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined.MethodsWe conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage.ResultsThe participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone).ConclusionsAmong patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.)

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

BackgroundCoronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive.The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events.MethodsPatients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded.DiscussionThis will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management.This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).

Relationship Between Endothelial Functions and Acetylsalicylic Acid Resistance in Newly Diagnosed Hypertensive Patients

We aimed to investigate the effects and dose dependency of aspirin on endothelial functions and prevalence of aspirin resistance in newly diagnosed hypertensive patients without previous drug therapy and development of cardiac complications. Acetylsalicyclic acid improves endothelial function. Fifty-eight hypertensive patients and 61 healthy subjects in the control group were included in the study. Endothelial functions of the patient and control groups were evaluated with brachial artery examination. Patient and control groups were divided into 2 groups. A total of 100 mg and 300 mg of aspirin were given to the separate groups for 1 week. After 1 week, endothelial functions were reevaluated and aspirin resistance examined with a platelet function analyzer (PFA-100; Dade Behring, Marbourg, Germany). Baseline flow-mediated dilatation (FMD) change percent in hypertensive patients was 9.8%, and it was significantly lower than in the control group (12%) (P < 0.001). Frequency of acetylsalicylic acid (ASA) resistance was 20% and 26% in control and hypertensive patient groups, respectively (P = not significant). ASA resistance was 28% and 24% in 100 mg and 300 mg in hypertensive patients, respectively (P = not significant). FMD change percent increased both in the control and hypertensive groups after ASA treatment from 12.4% to 13.3% and 9.8 % to 11.9 %, respectively. FMD percentage change was significantly increased in hypertensive patients irrespective of ASA resistance (P = 0.02, for ASA resistance [+]; P < 0.012, for ASA resistance [-]). Endothelial functions were impaired more in hypertensive patients compared to the control group. Endothelial functions were improved with all ASA doses in hypertensive patients irrespective of ASA resistance.

Eptifibatide for the Treatment of HeartMate II Left Ventricular Assist Device Thrombosis

Left ventricular assist device (LVAD) thrombosis is a life-threatening complication occurring in ≈6% of patients receiving a HeartMate II (HMII) LVAD (Thoratec Corp, Pleasanton, CA) within 24 months after implantation.1 Prophylactic therapy with aspirin and warfarin to an international normalized ratio (INR) of 1.5 to 2.5 is recommended to prevent LVAD thrombosis in most HMII recipients.2 For device malfunction because of pump thrombosis, surgical device exchange may be necessary but carries a high risk of morbidity and mortality. Alternate treatment approaches include the addition of clopidogrel, tirofiban, and thrombolysis.3 We report our experience with eptifibatide (Merck & Co, Inc, Whitehouse Station, NJ), a platelet glycoprotein IIb/IIIa receptor inhibitor, for the treatment of LVAD thrombosis in 2 patients. A 66-year-old male with ischemic cardiomyopathy who underwent HMII implantation as a bridge to cardiac transplantation developed LVAD thrombosis 42 days after his surgery while taking 325 mg of aspirin and warfarin. His INR was subtherapeutic at 1.3. Hematuria, a lactate dehydrogenase level of 2326 IU/L, direct bilirubin of 0.8 mg/dL, a lower pulsatility index, and pump flow compared with previous levels, which suggested hemolysis and …

Low-dose enteric-coated aspirin does not inhibit thromboxane B2 and prostaglandin E2: data-derived hypothesis formulation

Background: All usual daily doses of plain aspirin inhibit thromboxane B2 (TXB2) as well as prostaglandin E2 (PGE2). The role of 81-mg enteric-coated aspirin (ECA) is controversial. Method: In a randomized, double-blind trial, 37 patients (25 men and 12 women) with chronic stable coronary disease taking ECA 81 mg at baseline were assigned to plain aspirin 81, 162.5, 325, 650 or 1300 mg daily for 12 weeks. At baseline and 12 weeks, blood was tested for TXB2 and PGE2. Results: All doses of plain aspirin produced virtually identical reductions in TXB2 and PGE2. For all doses combined, the mean ratio of the 12-week to baseline value was 0.03 for TXB2 (p < 0.001) and 0.63 for PGE2 (p < 0.001). Conclusion: These data indicate that ECA 81 mg daily does not inhibit TXB2 and PGE2, markers of acute and systemic responses to aspirin. Randomized trials designed a priori to test this hypothesis are necessary.

Effects of preoperative aspirin in coronary artery bypass grafting: A double-blind, placebo-controlled, randomized trial

This trial was undertaken to determine the safety and efficacy of preoperative aspirin administration in a contemporary cardiac surgical practice setting. This randomized, double-blind, parallel-group, single-center trial involved patients with stable coronary artery disease who were assigned to receive either 300 mg of aspirin or placebo the night before coronary bypass surgery. Using a random digit table, patients were allocated to receive the tablet from 1 of the 40 coded bottles containing either aspirin or placebo. Patients, surgeons, anesthetists, and investigators were all masked to treatment allocation. The primary safety end points were as follows: more than 750 mL of bleeding during the first postoperative 12 hours and more than 1000 mL of total discharge from the chest drains. The secondary efficacy end point was a composite of cardiovascular death, myocardial infarction, or repeat revascularization. A total of 390 patients were allocated to aspirin (387 analyzed) and 399 to placebo (396 analyzed). The follow-up median was 53 months. Fifty-four placebo recipients and 86 aspirin recipients bled more than 750 mL in the first 12 hours (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.25-2.63), while total chest drain discharge was above 1000 mL in 96 placebo and 131 aspirin recipients (OR, 1.60; 95% CI, 1.17-2.18). Preoperative aspirin decreased the long-term hazard of nonfatal coronary event (infarction or repeat revascularization)-hazard ratio (HR), 0.58 (95% CI, 0.33-0.99)--and tended to decrease the hazard of a major cardiac event (cardiovascular death, infarction, or repeat revascularization--HR, 0.65 [95% CI, 0.41-1.03]). Performing coronary grafts on aspirin is associated with increased postoperative bleeding but may decrease the long-term hazard of coronary events.

Lobar cerebral microbleeds associated with transient focal neurological symptoms followed by symptomatic intracerebral hemorrhage

Cerebral microbleeds (CMBs) are defined as all discrete round-shaped hypointense areas on T2*-weighted magnetic resonance images (MRIs) with a gradient-echo (GRE) sequence [11]. CMBs can be regarded as a marker of vessel wall disorders with a higher tendency for intracerebral hemorrhage (ICH) [11]. It has been suggested that microbleeds increase the risk of ICH following antithrombotic administration for acute ischemic stroke [9, 14], though this issue remains controversial. In addition, there have been few reports of symptomatic ICH that has occurred at the site of microbleeds in the literature [2, 13]. However, these lesions themselves have been considered asymptomatic. We present a case of CMBs presenting with transient neurologic symptoms that developed into subsequent ICH. A 65-year-old man with no previous neurological history visited our hospital because of incoherent speech and headache. He had a history of diabetes mellitus and chronic hepatitis B. He had been diagnosed with hepatocellular carcinoma prior to this presentation. Neurological examination revealed that he had language disturbances with jargon speech and abnormal comprehension. These symptoms fluctuated and persisted for about half an hour after symptom onset. The results of other physical examinations were normal. Electroencephalography showed that there were no epileptiform discharges or abnormal inherent rhythms. There were also no acute ischemic brain lesions or hemorrhages on initial brain MRI (Fig. 1a). GRE images showed multiple CMBs in the left temporo-parieto-occipital lobe relevant to language disturbance (Fig. 1b). However, there were no CMBs in the deep subcortical area and brainstem. There were no CMBs on previous GRE images obtained at a local clinic 1 month prior to this presentation as well (Supplemental Figure). While he had no symptoms at this time, he underwent brain MRI as part of a medical check-up. All laboratory tests, including coagulation profiles, were normal. He was tentatively diagnosed with (1) recurrent transient ischemic attacks and (2) mood disorder associated with medical condition. During admission, he was treated with antihypertensive agents and 100 mg of aspirin for prevention of secondary ischemic stroke. On the fourth day of admission, he suddenly developed global aphasia and right hemiparesis. Follow-up GRE images showed a large lobar hematoma with perilesional edema in the left temporo-parietal lobe where the CMBs were previously seen (Fig. 1c). Although he was referred to the Department of Neurosurgery for surgical management, he was discharged with a modified Rankin scale of 5. Our case illustrates that localized CMBs can be related to transient neurological symptoms and subsequent ICH. Although this is a single case that represents a causal relationship between CMBs and transient neurological symptoms, the association between CMBs and subsequent ICH could not be clarified, suggesting that transient Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6504-8) contains supplementary material, which is available to authorized users.