Early Administration Of Aspirin Research Articles

Early Use of Aspirin for Coronary Allograft Prophylaxis in Heart Transplant Recipients.

Coronary allograft vasculopathy (CAV) remains a significant cause of morbidity and mortality after heart transplantation. The use of aspirin for CAV prophylaxis has recently garnered interest as a possible therapeutic adjunct in this setting. This 2-center retrospective cohort study included 372 patients who underwent heart transplantation between January 2009 and March 2018 and were stratified according to the commencement of aspirin during their index transplant admission. The primary outcome was the development of moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) at surveillance coronary angiography. Secondary endpoints included mortality at follow-up. There were no differences in age, sex, and cause of heart failure. In the early aspirin group, the preponderant risk factors included use of ventricular assist devices, pretransplant smoking, and mild or moderate rejection. Multivariable analyses to assess for independent predictors of CAV development and mortality demonstrated that aspirin was associated with reduced mortality (adjusted hazard ratio = 0.19; 95% confidence interval, 0.08-0.47, P < 0.01) and a trend toward a protective effect against the development of moderate or severe CAV (adjusted hazard ratio = 0.24; 95% confidence interval, 0.54-1.19; P = 0.08). In this retrospective risk-adjusted 2-center cohort study, early aspirin administration was associated with reduced risk of death and a trend toward a protective effect against CAV development. These findings warrant validation in prospective randomized trials.

Aspirin Administration Mitigates Platelet Hyperaggregability After Splenectomy in a Murine Model

IntroductionPatients who undergo splenectomy (SPLN) have an estimated 10%-35% risk of venous thromboembolic events; however, the underlying mechanism and strategy for prevention have yet to be identified. The goals of this study were to 1) investigate platelet aggregation after SPLN, 2) examine if aspirin administration could mitigate this effect, and 3) determine if concomitant hemorrhage would affect post-SPLN platelet function and response to aspirin. MethodsMurine models of operative SPLN and submandibular bleed (SMB) were utilized. Mice were randomized to eight groups as follows: untouched, SPLN, sham (laparotomy only), SMB, SPLN + SMB, SPLN + aspirin (ASA), SMB + ASA, and SPLN + SMB + ASA. Aspirin (50 mg/kg) was administered on postoperative days (PODs) one and two via oral gavage. Mice were euthanized on POD 3, platelet counts were obtained, and blood samples were analyzed via rotational thromboelastometry and impedance aggregometry with adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists. ResultsBy POD 3, SPLN mice displayed a significant thrombocytosis compared to untouched, SMB, and sham SPLN mice. Clotting time and clot formation time were significantly decreased in SPLN and SPLN + SMB cohorts compared to untouched and sham controls with elevated mean clot firmness. SPLN mice also displayed a significant increase in ADP- and AA-mediated platelet aggregability compared to untouched controls, SMB, and SPLN + SMB. ASA significantly decreased platelet aggregation via both ADP and AA signaling in SPLN and SPLN + SMB cohorts without affecting viscoelastic coagulation testing. ConclusionsPlatelet hyperaggregability after SPLN is mediated by both ADP and AA signaling. Early aspirin administration may prevent increased platelet aggregation exacerbated after polytrauma.

Pathophysiology and Mechanisms of Saphenous Vein Graft Failure.

IntroductionCoronary artery bypass grafting remains one of the best therapies for advanced coronary artery disease. The most used conduit remains the great saphenous vein, which is susceptible to short-term and long-term failure, the result of acute thrombosis, intimal hyperplasia, and late superimposed atheroma. In this review, we present the current findings related to the pathophysiology of vein graft failure.MethodsA search of three databases - MEDLINE®, Web of Science™, and Cochrane Library - was undertaken for the terms “pathophysiology”, “prevention”, and “treatment” plus the term “vein graft failure”.ResultsThe pathophysiology of saphenous graft failure can be classified in three distinct phases - acute thrombosis, intimal hyperplasia, and accelerated atherosclerosis. All these processes start with an underlying histological predisposition of the vein and at the time of harvesting and preparation for grafting. These mechanisms are a result of localized inflammatory and prothrombotic cascades that obey different causes, but ultimately result in the stenosis or occlusion of the vein graft.ConclusionThe interaction between the different parts of the pathophysiology of vein graft failure is extremely complex and variable. Recent improvements in surgical techniques and secondary pharmaceutical prevention like early aspirin administration and long-term statin treatment have significantly reduced early and late saphenous vein graft failure. However, this continues to be a fascinating area of research with the potential for further improvement for patients and health service provision.

The Analgesic Effect of Aspirin on Inflammatory Pain in Rats Is Affected by Pain Intensity and Administration Timing

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely known as painkillers. The analgesic action of NSAIDs is attributable to the inhibition of prostaglandin synthesis that occurs in response to blocking cyclooxygenase activity. The effective dose of NSAIDs can vary depending on pain intensity and administration timing; however, there are few studies on this. This study aimed to elucidate whether the analgesic effect of NSAIDs changes depending on the situation in which they are taken and we focused on the NSAID, aspirin (ASP). In a rat model of brewer's yeast-induced inflammation, pain caused by 20% (w/v) brewer's yeast-treatment was defined as "strong pain" and that caused by 2.5% (w/v) was defined as "weak pain". The analgesic effect of ASP (low-dose; 44 mg/kg or high-dose; 66 mg/kg) against strong pain was dose-dependent, but that against weak pain was the same. Furthermore, we defined drug administration after 3 h of brewer's yeast-treatment as "late administration" and that after 20 min as "early administration". In the case of strong pain, the analgesic effect of "late ASP administration" was dose-dependent, but that of "early ASP administration" was the same. These results suggest that low-dose NSAIDs have an analgesic effect against weak pain or when taken early.

Sex Differences in Care and Long-Term Mortality After Stroke: Australian Stroke Clinical Registry.

Introduction: There is some evidence that women receive evidence-based care less often than men, but how this influences long-term mortality after stroke is unclear. We explored this issue using data from a national stroke registry. Materials and Methods: Data are first-ever hospitalized strokes (2010-2014) in the Australian Stroke Clinical Registry from 39 hospitals linked to the national death registrations. Multilevel Poisson regression was used to estimate the women:men mortality rate ratio (MRR), with adjustment for sociodemographics, stroke severity, and processes of care (stroke unit care, intravenous thrombolysis, antihypertensive agent[s], and discharge care plan). Results: Among 14,118 events (46% females), women were 7 years older and had greater baseline severity compared to men (29% vs. 37%; p < 0.001), but there were no differences in the four processes of care available across hospitals. In the whole cohort, 1-year mortality was greater in women than men (MRRunadjusted 1.44, 95% confidence interval [CI] 1.34-1.54). However, there were no differences after adjusting for age and stroke severity (MRRadjusted 1.03, 95% CI 0.95-1.10). In analyses of additional processes from Queensland hospitals (n = 5224), women were less often administered aspirin ≤48 hours (61% vs. men 69%, p < 0.015). In Queensland hospitals, there were no statistically significant sex differences in 1-year mortality after adjusting for age, stroke severity, and early administration of aspirin. Conclusion: Greater mortality in women can be explained by differences in age and stroke severity. This highlights the importance of better management of risk factors in the elderly and, potentially, the need for greater access to early aspirin for women with stroke.

Prediction and prevention of pre‐eclampsia in Asian subpopulation

The benefit of the early administration of aspirin to reduce preterm pre-eclampsia among screened positive European women from multivariate algorithmic approach (ASPRE trial) has opened an intense debate on the feasibility of universal screening. This review aims to assess the new perspectives in the combined screening of pre-eclampsia in the first trimester of pregnancy and the chances for prevention using low-dose aspirin with special emphasis on the particularities of the Asian population. PubMed, CENTRAL and Embase databases were searched from inception until 15 November 2017 using combinations of the search terms: preeclampsia, Asian, prenatal screening, early prediction, ultrasonography, pregnancy, biomarker, mean arterial pressure, soluble fms-like tyrosine kinase-1, placental growth factor, pregnancy-associated plasma protein-A and pulsatility index. This is not a systematic review or meta-analysis, so the risk of bias of the selected published articles and heterogeneity among the studies need to be considered. The prevalence of pre-eclampsia and serum levels of biochemical markers in Asian are different from Caucasian women; hence, Asian ethnicity needs to be corrected for in the algorithmic assessment of multiple variables to improve the screening performance. Aspirin prophylaxis may still be viable in Asian women, but resource implication needs to be considered. Asian ethnicity should be taken into account before implementing pre-eclampsia screening strategies in the region. The variables included can be mixed and matched to achieve an optimal performance that is appropriate for economical restriction in individual countries.

Early Aspirin administration post Coronary Artery Bypass Graft Surgery – Changing hospital culture through a two-cycled audit

“Early Aspirin” or a medium dose of aspirin 6 hours after Coronary Artery Bypass Graft (CABG) Surgery is strongly recommend by international guidelines (EACTS 2007/AHA 2011 guidelines, Level1a evidence) to...

Management of acute ischemic stroke

Targets of acute ischemic stroke management include verification of clinical diagnosis, start of basic care and decision-making about specific treatments.Effectiveness of most therapeutic options is time dependent. Time delays within the rescue chain are associated with worse outcome. Trained and multidisciplinary teams on Stroke Unit form the backbone of acute management. Moreover, technical infrastructure influences therapeutic options. Cerebral imaging is pivotal.The following five therapies are evidence-based: treatment on a stroke unit, thrombolysis within 4.5hrs after symptom onset, mechanical recanalization in patients with occlusion of proximal, intracranial arteries, early administration of Aspirin, and hemicraniectomy in patients with so-called malignant infarction.This article describes the necessary diagnostic steps and specific as well as non-specific therapeutic options that compose acute management within the first 72 hours.

Early prediction and aspirin for prevention of pre-eclampsia (EPAPP) study: a randomized controlled trial.

To estimate the effect of early administration of aspirin on the prevention of pre-eclampsia in high-risk women. This was planned as a randomized, double-blind, placebo-controlled trial of aspirin for women with risk factors for pre-eclampsia. Participants were randomized to start either aspirin (81 mg/day) or placebo at 11 + 0 to 13 + 6 weeks of gestation. The primary outcome was pre-eclampsia and secondary outcomes included gestational hypertension and small-for-gestational age at birth. The trial suffered from slow recruitment, leading to a protocol change to broaden the inclusion criteria (from a minimum score of multiple risk factors to at least one risk factor for pre-eclampsia). The trial was then terminated prematurely due to continuing slow recruitment and a lack of equipoise given a change in national guidelines to administer aspirin to high-risk women. From the 53 women who were randomized, 30 were included in the final analysis. There was no evidence that the primary outcome of pre-eclampsia was prevented by low-dose aspirin (relative risk (RR) 0.88, 95% CI 0.21-3.66). Gestational hypertension was seen in two women, both in the aspirin group. There was no evidence that the occurrence of small-for-gestational age was reduced by aspirin (RR 0.88, 95% CI 0.06-12.72). Although this study was underpowered to show effectiveness of aspirin compared to placebo due to the premature termination and difficulties encountered, it highlights practical issues to inform future studies.

Prehospital aspirin administration for acute coronary syndrome (ACS) in the USA: an EMS quality assessment using the NEMSIS 2011 database

IntroductionNational practice guidelines recommend early aspirin administration to reduce mortality in acute coronary syndrome (ACS). Although timely administration of aspirin has been shown to reduce mortality in ACS by 23%,...

Does Early Post-operative Administration of Aspirin Influence the Risk of Bleeding After Coronary Artery Bypass Graft Surgery? A Prospective Observational Study.

Background:Aspirin has a proven role in preventing thrombotic diseases. However, given its anti-platelet activity, it is often assumed that its early post-operative administration significantly increase the amount of post-operative bleeding.Aim:The aim of this study was to determine whether early post-operative administration of aspirin influence the risk of bleeding in patients undergoing coronary artery bypass graft (CABG) surgery.Methods:In a prospective observational study, 100 consecutive patients undergoing first time elective CABG surgery were include in the study. Patients received a low dose of aspirin (75-150 mg per day) either 1 hours (the early aspirin group; n=43) or 6 hours after surgery (the late aspirin group; n=57). Total mediastinal blood drainage, blood drainage after 6 hours, incidences of re-operation for the control of bleeding and transfusion of red blood cells (RBCs) and blood products were recorded and followed until chest tube removal.Results:The groups were found to be matched for the confounding variables and no significant differences were found between post-aspirin bleeding (p=0.37), RBCs and blood product usage (p=0.90) or incidences of re-operation for control of bleeding (p=1.00) between the two groups.Conclusions:Early administration (1 hour after surgery) of aspirin did not appear to increase the risk of post-operative bleeding in patients undergoing CABG. Thereby, its early administration in such cases may be considered. Although further well-designed randomized controlled trials to confirm the safety and efficacy of early administration of aspirin after CABG surgery are warranted.

Pre-eclampsia part 2: prediction, prevention and management.

An antiangiogenic state might constitute a terminal pathway for the multiple aetiologies of pre-eclampsia, especially those resulting from placental abnormalities. The levels of angiogenic and antiangiogenic proteins in maternal blood change prior to a diagnosis of pre-eclampsia, correlate with disease severity and have prognostic value in identifying women who will develop maternal and/or perinatal complications. Potential interventions exist to ameliorate the imbalance of angiogenesis and, hence, might provide opportunities to improve maternal and/or perinatal outcomes in pre-eclampsia. Current strategies for managing pre-eclampsia consist of controlling hypertension, preventing seizures and timely delivery of the fetus. Prediction of pre-eclampsia in the first trimester is of great interest, as early administration of aspirin might reduce the risk of pre-eclampsia, albeit modestly. Combinations of biomarkers typically predict pre-eclampsia better than single biomarkers; however, the encouraging initial results of biomarker studies require external validation in other populations before they can be used to facilitate intervention in patients identified as at increased risk. Angiogenic and antiangiogenic factors might also be useful in triage of symptomatic patients with suspected pre-eclampsia, differentiating pre-eclampsia from exacerbations of pre-existing medical conditions and performing risk assessment in asymptomatic women. This Review article discusses the performance of predictive and prognostic biomarkers for pre-eclampsia, current strategies for preventing and managing the condition and its long-term consequences.

Who might benefit from early aspirin after coronary artery surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether early administration of aspirin might optimize vein graft patency. More than 250 papers were found using the reported search, of which 4 new papers in addition to the previous 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Early postoperative aspirin administered within 6 h following coronary artery bypass grafting (CABG) has been shown to be optimal for prevention of vein graft occlusion. Early aspirin has significant benefit in reducing vein graft occlusion, mortality, myocardial infarction, stroke, renal failure and bowel infarction. The efficacy of early postoperative aspirin on vein graft patency diminishes the later it is administered. It has optimal benefit at 6 h, some benefit at 24 h and no benefit after 48 h post CABG. ACC/AHA, EACTS and ACCP have issued guidelines recommending administration of early aspirin or an alternative (clopidogrel, ticlopidine and indobufen) at 6 h or soon after bleeding has settled as the standard of care for optimization of vein graft patency. The ACCP guideline has also suggested that optimal prevention of cardiovascular complication should have higher value than prevention of postoperative bleeding. Several randomized, controlled studies, including a meta-analysis, have shown that early administration of aspirin following CABG is not associated with increased blood loss or transfusion requirement. Postoperative bleeding has been identified as a significant reason for non administration of early aspirin in a prospective study. It is essential to define/quantify the postoperative blood loss that precludes administration of early aspirin. This will enhance prompt administration in some cases and guide judgement, especially in patients with high-risk factors for vein graft thrombosis. Administration at 6 h is the optimal time to give aspirin as long as bleeding has settled.

Out-of-Hospital Aspirin Administration for Acute Coronary Syndrome in the United States: An EMS Quality Assessment Using the NEMSIS (National EMS Information System) Database

Out-of-Hospital Aspirin Administration for Acute Coronary Syndrome in the United States: An EMS Quality Assessment Using the NEMSIS (National EMS Information System) Database

Outcomes for People with Atrial Fibrillation in an Australian National Audit of Stroke Care

Atrial fibrillation is associated with poorer outcomes poststroke. It is unclear how the quality of stroke care in hospitals influences outcomes in these patients. The study aims to compare outcomes in stroke patients with and without atrial fibrillation and identify hospital processes of care associated with poor outcomes. Data were collected using retrospective, consecutive medical record audits from participating hospitals in the 2009 and 2011 National Stroke Foundation acute services audit program. Patient characteristics, stroke severity, and hospital management data were compared for those with and without atrial fibrillation. Multiple regression analyses for outcomes of in-hospital death, dependency at discharge (modified Rankin Score 3-5), and discharge destination were undertaken, adjusted for patient clustering by hospital. Atrial fibrillation status was known for 5473 (80%) cases; 2049 had atrial fibrillation. Atrial fibrillation was independently associated with in-hospital mortality (aOR 1.46, 95% CI 1.06, 2.02). Management on a stroke unit (aOR 0.57, 95% CI 0.40, 0.80) and having a swallow assessment within 24 h (aOR 0.71, 95% CI 0.51, 0.98) were associated with increased survival among all stroke types, as was receiving aspirin within 48 h poststroke (aOR 0.65, 95% CI 0.44, 0.97), for patients with an ischemic stroke. Stroke patients with atrial fibrillation were less likely to receive important processes of care associated with reduced mortality. Hospital processes of care can influence outcomes in stroke patients with atrial fibrillation. The greater in-hospital mortality experienced by stroke patients with atrial fibrillation may be attenuated by admission to a stroke unit, and for ischemic stroke, early administration of aspirin.

Early Administration of Aspirin in Patients Treated with Alteplase for Acute ischemic Stroke: A Randomized Controlled Trial: Zinkstok S, Roos Y; on behalf of the ARTIS investigators. Lancet 2012;380:731–7.

Early Administration of Aspirin in Patients Treated with Alteplase for Acute ischemic Stroke: A Randomized Controlled Trial: Zinkstok S, Roos Y; on behalf of the ARTIS investigators. Lancet 2012;380:731–7.

Early Administration of Low-Dose Aspirin for the Prevention of Severe and Mild Preeclampsia

Objective: To compare the effect of early administration of aspirin on the risk of preterm and term preeclampsia. Method: A systematic review and meta-analysis of randomized controlled trials were performed. Women who were randomized to low-dose aspirin or placebo/no treatment at or before 16 weeks of gestation were included. The outcomes of interest were preterm preeclampsia (delivery ! 37 weeks) and term preeclampsia. Pooled relative risks (RR) with their 95% confidence intervals (CI) were computed. Results: The search identified 7,941 citations but only five trials on a combined total of 556 women fulfilled the inclusion criteria. When compared to controls, aspirin initiated ^ 16 weeks of gestation was associated with a major reduction of the risk of preterm preeclampsia (RR 0.11, 95% CI 0.04–0.33) but had no significant effect on term preeclampsia (RR 0.98, 95% CI 0.42–2.33). Conclusion: Low-dose aspirin administrated at or before 16 weeks of gestation reduces the risk of preterm but

Aspirin administration by emergency medical dispatchers using a protocol-driven aspirin diagnostic and instruction tool

BackgroundThe American College of Cardiology and the American Heart Association recommend early aspirin administration to patients with symptoms of acute coronary syndrome (ACS)/acute myocardial infarction (AMI). The primary objective of...

Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial

Thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. After alteplase-induced recanalisation, reocclusion occurs in 14-34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after alteplase could reduce the risk of reocclusion and improve outcome. We compared the effects of early addition of intravenous aspirin to alteplase with standard alteplase without aspirin. In this multicentre, randomised, open-label trial with blind-endpoint assessment, patients with acute ischaemic stroke treated with alteplase were randomly assigned to 300 mg intravenous aspirin within 90 min after start of alteplase treatment or to no additional treatment. In both groups, oral antiplatelet therapy was started 24 h after alteplase treatment. The primary endpoint was favourable outcome, defined as a score of 0-2 on the modified Rankin scale at 3 months. This trial is registered with the Netherlands Trial Register (NTR822). Between July 29, 2008, and April 20, 2011, 642 patients (322 patients aspirin, 320 patients standard treatment) of the targeted 800 patients were enrolled. At that time, the trial was terminated prematurely because of an excess of symptomatic intracranial haemorrhage (SICH) and no evidence of benefit in the aspirin group. At 3 months, 174 (54·0%) patients in the aspirin group versus 183 (57·2%) patients in the standard treatment group had a favourable outcome (absolute difference -3·2%, 95% CI -10·8 to 4·2; crude relative risk 0·94, 0·82 to 1·09, p=0·42). Adjusted odds ratio was 0·91 (95% CI 0·66-1·26, p=0·58). SICH occurred more often in the aspirin group (14 [4·3%] patients) than in the standard treatment group (five [1·6%]; absolute difference 2·8%, 95% CI 0·2-5·4; p=0·04). SICH was more often the cause of poor outcome in the aspirin group compared with the standard treatment group (11 vs 1, p=0·006). Early administration of intravenous aspirin in patients with acute ischaemic stroke treated with alteplase does not improve outcome at 3 months and increases the risk of SICH. The results of this trial do not support a change of the current guidelines, which advise to start antiplatelet therapy 24 h after alteplase. The Dutch Heart Foundation.

Early Administration of Low-Dose Aspirin for the Prevention of Severe and Mild Preeclampsia: A Systematic Review and Meta-Analysis

To determine whether early administration of aspirin prevents severe and mild preeclampsia. A systematic review and meta-analysis of randomized controlled trials were performed. Studies in which women were randomized at or before 16 weeks' gestation to low-dose aspirin versus placebo or no treatment were included. The outcomes of interest were severe preeclampsia and mild preeclampsia. Pooled relative risks with their 95% confidence intervals (CIs) were calculated. Among 7941 citations retrieved, 352 were completely reviewed and four studies (392 women) fulfilled the inclusion criteria and were analyzed. When compared with controls, aspirin started at ≤16 weeks was associated with a significant reduction in severe (relative risk: 0.22, 95% CI: 0.08 to 0.57) but not mild (relative risk: 0.81, 95% CI: 0.33 to 1.96) preeclampsia. Low-dose aspirin initiated at or before 16 weeks reduces the risk of severe preeclampsia, but not mild preeclampsia.