High-dose Aspirin Research Articles

Efficacy of dupilumab in patients with aspirin-exacerbated respiratory disease and previous inadequate response to anti-IL-5 or anti-IL-5Rα in a real-world setting

Aspirin-exacerbated respiratory disease (AERD), the triad of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and respiratory reactions to cyclooxygenase-1 inhibitors, is characterized by difficult-to-treat upper and lower respiratory symptoms. It is a type 2–mediated inflammatory disease marked by blood and tissue eosinophilia, dysregulated cysteinyl leukotriene production, and mast cell activation.1 Nasal polyposis in AERD is often severe and refractory to standard-of-care management including topical and systemic corticosteroids, endoscopic sinus surgery (ESS), and aspirin desensitization followed by high-dose daily aspirin.

First reported case of Multisystem Inflammatory Syndrome in children in West Texas

Research focusing on COVID-19-associated complications has become a growing area of importance. One such complication is multisystem inflammatory syndrome, a rare immune-mediated condition that most commonly presents with Kawasaki-like symptoms in the pediatric population. Potential complications include myocarditis, renal impairment, and cytokine storm. Here we describe the first reported case of multisystem inflammatory syndrome in the West Texas region, presenting in a Hispanic 5-year-old female with a recent history of COVID-19. The patient arrived to the hospital with a 4 day history of high fever, a 2 day history of diffuse maculopapular rash, and complaints of fatigue, generalized body aches, decreased appetite, headache, and abdominal pain. Further physical exam revealed hepatosplenomegaly and cervical lymphadenopathy, while labs revealed elevated inflammatory markers, lymphopenia, left shift with bandemia and immature cells, thrombocytopenia, hypoalbuminemia, and transaminitis. The patient was admitted to the pediatric intensive care unit with a suspected Kawasaki-like illness and started on high dose aspirin and IV immunoglobulin. She was placed on methylprednisolone, albumin, and acetaminophen on hospital day 3. By hospital day 4, the patient defervesced, inflammatory markers decreased, and clinical symptoms improved. The patient was discharged on hospital day 10 with absent fever and improvement of clinical symptoms for 6 consecutive days. No complications were detected upon follow-up 2 weeks later. A low threshold of suspicion for this illness is required in any child with a history of SARS-CoV-2 infection, as the presentation is vague and early identification is necessary to prevent further complications.

Pharmacologic Interventions for Kawasaki Disease in Children: A Network Meta-Analysis of 56 Randomized Controlled Trials

Background: Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial stage and the refractory stage of KD. Methods: The current NMA of randomized controlled trials (RCTs) was conducted under the frequentist model. Findings: Total fifty-six RCTs with 6,486 participants were included. The NMA demonstrated that the medium intravenous immunoglobulin (IVIG) + aspirin + infliximab [mean difference=−1.76 days (95% confidence intervals (95%CIs): −3.65 to 0.13 days) compared to high IVIG + aspirin] had the shortest fever duration; likewise, the medium IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95%CIs: 0.18 to 1.37 compared to high IVIG + aspirin] had the least CAL incidence in the initial-stage KD. The high IVIG + pulse steroid therapy (OR=0.04, 95%CIs: 0.00 to 0.43 compared to the high IVIG only) had the best fever subsided rate; likewise, the high IVIG + ciclosporin [OR=0.05 (95%CIs: 0.00 to 1.21) compared to the high IVIG only] had the least CAL incidence in the refractory-stage KD. Interpretation: The current NMA demonstrates that the addition of infliximab plus current standard therapy might be the best treatment for acute KD. Conversely, ciclosporin plus IVIG serves as the best choice for lower the CAL incidence in refractory KD. Further controlled trials are warranted to confirm these findings. Funding Statement: The authors of this work did not receive any grant supports. Brendon Stubbs is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR). Brendon Stubbs is part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. Brendon Stubbs is also supported by the Maudsley Charity, King’s College London and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. This paper presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions. Declaration of Interests: The authors report no financial interests or potential conflicts of interest.

Can aspirin use reduce the risk of pancreatic cancer: an updated systematic review and meta-analysis

Abstract Background: Chemoprevention effect of aspirin for pancreatic cancer (PC) remains unclear. Here we performed an updated systematic review and meta-analysis to investigate the real association between aspirin consumption and risk of PC. Methods: PubMed, Web of Science, EMBASE and the Cochrane Database were systematic searched to identify the potential studies. Odds ratio (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of associations. Results: Thirteen studies and approximately 28,440 participants were included. Aspirin significantly reduced the incidence of PC (OR, 0.82; 95% CI, 0.73–0.93) in case-control studies. However, the overall results did not reveal an obvious association (OR, 0.92; 95% CI, 0.74–1.16). Both low-dose (OR = 0.86) and high-dose (OR = 0.80) aspirin intake showed prevention effect. In addition, low frequency (OR, 0.87; 95% CI, 0.73–1.05) and high frequency (OR, 0.84; 95% CI, 0.69–1.03) seemed to be equally associated with decreased risk for PC. Aspirin consumption longer than 10 years use seems to have better effect (OR, 0.73; 95% CI, 0.51–1.04) than shorter aspirin use (OR, 0.94; 95% CI, 0.77–1.15). Conclusions: Our study indicated that aspirin use might be associated with decreased risk of PC, especially at high doses. But we still need to be cautious when interpreting the results.

Resistant Kawasaki Disease in an Infant Causing Giant Coronary Aneurysms with Thrombosis

Giant coronary artery aneurysms that occur in 0.5 to 1% of patients with Kawasaki disease can be fatal if associated with thrombosis. Some patients may show persistent inflammation and fever despite treatment with repeated doses of intravenous immunoglobulin (IVIG), steroids, and aspirin. This report describes an infant boy with resistant Kawasaki disease who presented with extensive coronary artery involvement and coronary thrombosis. His inflammation was not controlled with multiple doses of IVIG, parenteral and oral steroids, or high-dose aspirin, and he finally needed infliximab, a monoclonal antibody against tumor necrosis factor alpha.

Low-dose or no aspirin administration in acute-phase Kawasaki disease: a meta-analysis and systematic review

ObjectiveTo compare the efficacy of low-dose or no aspirin with conventional high-dose aspirin for the initial treatment in the acute-phase of Kawasaki disease (KD).DesignA meta-analysis and systematic review of randomised...

Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)

Introduction:Paediatric Inflammatory Multisystem Syndrome - temporally associated with SARS-CoV2 (PIMS-TS) is a newly described syndrome during the COVID-19 pandemic. It is characterised by a state of persistent fever, inflammation and organ dysfunction following exposure to SARS-CoV-2 virus. It shares similar clinical features to Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. Like adult COVID-19 infection, profound inflammatory response significantly increases the risk of thromboembolism, which is a major cause of morbidity and mortality. In this review we share our experience, observation and prevention strategy with regard to thromboembolism in PIMS-TS.Method:Between the period of 14th March 2020 to 31st May 2020, Evelina London Children's Hospital admitted 68 patients with PIMS-TS from the South Thames Network. Patients were broadly treated with a combination of high dose aspirin and immunomodulation in the initial period. Realising its pro-thrombotic potential, from 1st May 2020, treatment strategy was changed to incorporate prophylactic subcutaneous low molecular weight heparin (dalteparin 100units/kg once daily) in combination with low dose aspirin (5mg/kg once daily, maximum 75mg) when a working diagnosis of PIMS-TS was made. We retrospectively collected data to understand the prevalence and pattern of thromboembolism in this cohort of patients.Results:Five patients (7.4%) developed thromboembolic complications during their acute illness with 6 recorded events overall. (Table 1) Three events happened without prophylactic anticoagulation cover. Four (5.9%) were cardiovascular/arterial events and 2 (2.9%) were venous thromboembolism. Those who required ventilation support and extracorporeal membrane oxygenation (ECMO) were associated with higher thrombotic rate using 2-tailed Fisher's exact test (ventilation: p=0.02; ECMO: p=0.004). One ischaemic cerebrovascular event resulted in death. Two bleeding events were recorded whilst on anticoagulation. One was iatrogenic following arterial line insertion and another a haemorrhagic transformation from an ischaemic stroke.Coagulation markers (fibrinogen and D-dimer) followed the overall pattern observed in inflammatory markers (ferritin and C-reactive protein) on admission, at peak values and at 2-week follow up, suggesting a connection between the degree of inflammation and hypercoagulability and inferring immunothrombosis. (Table 2) Peak ferritin and D-dimer levels were significantly higher in the group with thromboembolism using 2-tailed Mann-Whitney U test (ferritin: p=0.038; D-dimer: p=0.034).Conclusion:Thromboembolism needs to be considered as a significant complication in patients with a diagnosis of PIMS-TS. We observed more cardiovascular/arterial events than venous events, which coincided with the fact that PIMS-TS patients commonly develop cardiac involvement and coronary abnormalities. In addition to rapid correction of hyper-inflammatory state using immunomodulation, we suggest the consideration of low dose aspirin (5mg/kg once daily, maximum 75mg) and prophylactic dalteparin (100units/kg once daily) to prevent both arterial and venous thrombosis after careful individual assessment and exclusion of co-existing factors that can cause increased bleeding risk. This may be especially relevant in those with already raised ferritin and D-dimer levels on admission.DisclosuresInusa:Vertex: Research Funding; AstraZeneca: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Bluebird bio: Research Funding; Novartis: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau.

Moment of truth for aspirin use in variant angina: a meta-analysis

Abstract Background Aspirin has been a mainstay of antiplatelet therapy for coronary artery disease (CAD). However, in the context of variant angina (VA), high-dose aspirin was reported to exacerbate coronary spasms. Consequently, the value of traditional low-dose aspirin in VA, especially if not associated with atherosclerotic CAD, may be disputed. Purpose To perform a meta-analysis aimed at evaluating the extent to which low-dose aspirin therapy influences cardiovascular (CV) prognosis in VA. Methods We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar for studies addressing the long-term impact of low-dose aspirin on main CV outcomes of VA patients, published up until February 1, 2020. The primary endpoint was all-cause mortality, whereas secondary endpoints included CV mortality, acute coronary syndrome (ACS) events, revascularization procedures and hospital admissions for angina. The subgroup of patients with no significant epicardial CAD was further investigated separately, underneath similar outcomes. Study-specific odds ratios (ORs) were pooled using traditional meta-analytic techniques, under a random-effects model. Results One prospective multicenter and two retrospective single-center studies, encompassing 1652 and 1164 patients, respectively, were regarded as eligible for quantitative evaluation. Median follow-up ranged between 12 and 52.1 months. 1284 patients were allocated to the aspirin arm and 2770 had no epicardial CAD. Absolute number of events for each endpoint may be reported as follows: all-cause mortality, 33; CV mortality, 11; ACS, 57; revascularization, 14; hospital admission for angina, 218. Aspirin was not found to reduce neither all-cause mortality (OR 0.78, 95% CI 0.38–1.58, p=0.49, i2=0%), nor CV mortality (OR 0.98, 95% CI 0.30–3.25, p=0.98, i2=0%), nor ACS events (OR 1.44, 95% CI 0.51–4.10, p=0.49, i2=47%), nor revascularization procedures (OR 2.06, 95% CI 0.63–6.75, p=0.23, i2=0%), nor hospital admissions for angina (OR 1.60, 95% CI 0.67–3.80, p=0.29, i2=86%). Likewise, this comprehensively neutral effect held true in those with VA and no significant atherosclerotic CAD (OR 1.04, 95% CI 0.28–3.92, p=0.95, i2=0%, for CV mortality; OR 1.29, 95% CI 0.19–8.94, p=0.79, i2=33%, for revascularization; OR 1.73, 95% CI 0.81–3.73, p=0.16, i2=75%, for hospital admission for angina). Conclusion Even though scarce, currently available evidence suggests that low-dose aspirin is not effective in shrinking major adverse cardiovascular events in VA patients, particularly in those with no epicardial CAD. On the other hand, lower doses of aspirin may avoid the menace of clinically significant coronary spasms. Funding Acknowledgement Type of funding source: None

Effectiveness and safety of high dose clopidogrel plus aspirin in ischemic stroke patients with the single CYP2C19 loss-of-function allele: a randomized trial

BackgroundDual antiplatelet aggregation therapy leads to better outcomes in patients with carotid artery stenosis, intracranial artery stenosis, minor strokes, or transient ischaemic attacks. However, carriers of the CYP2C19 loss-of-function allele may not experience the desired effects. We attempted to increase the clopidogrel dose to determine whether it would improve the outcomes of stroke patients who carry a single loss-of-function allele.MethodsWe recruited 131 patients with minor ischaemic stroke, within less than 7 days of stroke onset and a CYP2C19 loss-of-function allele, who had moderate-to-severe cerebral artery stenosis. Patients were divided into the high dose group (clopidogrel 150 mg per day + aspirin 100 mg per day over 21 days.) and a normal dose group (clopidogrel 75 mg per day + aspirin 100 mg per day over 21 days). The reported outcomes included any vascular or major bleeding events as the primary and safety endpoints, respectively.ResultsOne and six vascular events occurred in the high dose and normal dose groups during the 3-months follow-up period, respectively. However, no significant difference was found between the two groups when adjusted for history of diabetes (hazard ratio, 5482; 95% confidence interval, 0.660 to 45.543; P = 0.115). No major bleeding events occurred.ConclusionsIn patients with ischaemic stroke who had a single CYP2C19 loss-of-function allele and moderate to severe cerebral stenosis, fewer vascular events occurred within 3 months with high dose of clopidogrel and aspirin than with normal dose of clopidogrel and aspirin. However, the difference between the two groups was not significant.Trial registrationClinical study of clopidogrel in the treatment of patients with symptomatic moderate to severe cerebral artery stenosis with intermediate metabolites of CYP2C19, URL: http://www.chictr.org.cn/. Unique identifier: ChiCTR1800017411, 07/28/2018;

Mepolizumab does not prevent all aspirin-induced reactions in patients with aspirin-exacerbated respiratory disease: A case series

Aspirin-exacerbated respiratory disease (AERD) is a syndrome that includes nasal polyposis, asthma, and nonsteroidal anti-inflammatory drug sensitivity. This clinical triad is seen in about 7% of adults with asthma, and in about 15% of those with severe asthma,1 with the average age of onset being 34 years. A positive aspirin-induced reaction during a provocative aspirin challenge is the current standard for confirmative diagnosis.2 Aspirin desensitization, followed by initiation of daily high-dose aspirin therapy, is often used to help reduce nasal polyposis and asthma symptoms in these patients.

Abstract 1133: Risk effect of primary prevention strategy with aspirin on lung cancer incidence depends on high-level use, bodyweight and age: A U.S. adults evidence

Abstract Chemoprevention of cancer with aspirin is of particular interest as a primary prevention strategy, which was still in controversial. Using 101,462 individual participants' data from a U.S. adult's cohort, Cox regression model was used to detect the aspirin dosage effect on lung cancer risk. We calculated the effects of irregular use, low-dose use, and high-dose use of aspirin on lung cancer risk in population stratified by bodyweight and age. High-dose use of aspirin raised up 28% risk of lung cancer compared to no use (HR = 1.28, 95%CI = [1.14-1.45], P = 3.37×10-5). Meanwhile, the risk effect of high-dose aspirin significantly decreased with bodyweight increasing, indicating an antagonistic interaction (HRinteraction = 0.96, 95%CI = [0.94-0.99], P = 1.26×10-2). Furthermore, for these participants prone to lung cancer with bodyweight less than 80 kg, high-dose aspirin usage showed an elevated risk if their age less than 76 (HRage≤76 = 1.47, 95%CI = [1.25-1.73], P = 3.81×10-6), but did not exhibit risk effect in elders (HRage>76 = 1.13, 95%CI = [0.46-2.69], P = 0.80). The three-way interaction among dose of aspirin, bodyweight and age indicated that these vulnerable people (age ≤76 years and bodyweight <80 kg) with high lung cancer risk should be cautious to use high-dose aspirin for lung cancer chemoprevention. Citation Format: Xuesi Dong. Risk effect of primary prevention strategy with aspirin on lung cancer incidence depends on high-level use, bodyweight and age: A U.S. adults evidence [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1133.

Aspirin desensitization vs biologics for patients with aspirin-exacerbated respiratory disease

As the director of one of the largest evaluation and treatment centers for patients with aspirin-exacerbated respiratory disease (AERD) in the world, I am often asked on how we should approach the use of aspirin desensitization followed by high-dose aspirin therapy for our patients with AERD in the current age of newly available biologics. I feel strongly that, at least for now, there is a place for both treatment modalities, sometimes even both in the same patient at the same time. In the end, it is always a set of decisions that need to be made on an individual patient basis, and I consider the following 4 general domains when approaching the decision and my recommendation: efficacy, safety, cost, and patient preference.

Kawasaki disease: Shedding light on a mysterious diagnosis.

Kawasaki disease is an acute systemic febrile vasculitis of medium and small arteries, most often occurring in children under age 5 years. This condition is the most common cause of acquired heart disease in children in the developed world. The cause is unclear but is thought to be a hyperimmune reaction to an infectious agent. Diagnosis is clinical; the classic presentation includes persistent fever, lymphadenopathy, oral mucosal changes, conjunctivitis, and rash. Although the disease technically is self-limiting, treatment with IV immunoglobulin (IVIG) and high-dose aspirin is necessary to prevent cardiac complications, such as coronary artery aneurysm, pericarditis, or myocarditis. This article reviews the pathophysiology, clinical presentation, diagnosis, and treatment of Kawasaki disease.

Aspirin and Reducing Risk of Gastric Cancer: Systematic Review and Meta-Analysis of the Observational Studies.

The latest meta-analysis on the role of aspirin on various cancers was published in early 2018. By including the latest and updated primary observational studies, we aimed to conduct this systematic review and meta-analysis to synthesize stronger evidence on the role of aspirin in reducing gastric cancer (GC) risk. The PubMed, Scopus, and MEDLINE databases were systematically searched up to December 2019 to identify relevant studies. Random-effects model was used to calculate summary ORs and 95%CI for I 2 >50%. If the heterogeneity is not significant, the fixed-effects model was used. Overall analysis of the studies, inverse variance weighting after transforming the estimates of each study into log OR and its standard error were used. 21 studies were included in this meta-analysis. Results showed that aspirin significantly reduced the GC risk (OR=0.64, 95%CI=0.54-0.76) with substantial heterogeneity (I 2 =96%). Effect of GC risk reduction in low dose (OR=0.80, 95%CI=0.59-1.09) is slightly greater than high dose aspirin (OR=1.08, 95%CI=0.77-1.52). Protective effect of aspirin uses >5 years (OR=0.67, 95%CI=0.34-1.31) was greater than <5 years (OR=1.01, 95%CI=0.72-1.43) Conclusion: In conclusion, this meta-analysis showed that low dose aspirin with longer duration of more than 5 years were associated with a statistically significant reduction in GC risk. However, due to possible confounding variables and bias, these results should be cautiously treated.

Mo1289 SAFETY AND FEASIBILITY OF SAME DAY DISCHARGE FOLLOWING ESOPHAGEAL ENDOSCOPIC SUBMUCOSAL DISSECTION

Endoscopic submucosal dissection (ESD) is an endoscopic resection technique used for the treatment of early luminal gastrointestinal cancer. ESD has become standard of care in East Asia, where it results in a multi-day hospital admission for observation. Similarly, in the US, standard of care usually involves at least an overnight hospital stay. There is, however, limited data regarding practice in Western hospitals. To evaluate the safety and feasibility of same day discharge (SDD) following esophageal ESD. This is a retrospective cohort study of adults who underwent esophageal ESD with a Clutch Cutter device (DP2618DT; Fujifilm Corporation, Tokyo, Japan) at Mayo Clinic (Rochester, MN) from 2017-2019. The primary end point was post-procedural complications within 7 d of ESD, including need for physician phone call, Emergency Department visit, rehospitalization, and medical or endoscopic intervention. Of 96 patients (75% male, mean age 70±10.3 y) undergoing a total of 140 ESDs, 85 (60.7%) were SDDs vs 55 (39.3%) who were admitted. Of the 55 admits, 53 (96.4%) were discharged within 24 h, while 2 (3.6%) were admitted 2-3 d due to hypertensive urgency and TIA unrelated to ESD. SDD patients vs admits were similar in mean age (69.2 vs 71.4 y; p0.22) and sex (75.3% vs 71.4%; p0.84). However, admits were more likely to have a history of antiplatelet/anticoagulant (AP/AC) use (56.4% vs 34.1%; p0.01) and higher mean ASA physical status score (3.2 vs 2.9; p0.007). Admits had larger resections (28.6 vs 20.1 mm; p<0.0001) with longer durations (103.4 vs 62 min; p<0.0001). No difference in fibrosis was noted (12.7% vs 17.6%; p0.48). Among SDDs, no intraprocedural or post-procedural complications were seen. Among admits, 1 (1.8% vs 0%; p0.39) experienced intraprocedural bleeding requiring endoscopic intervention, 1 required transfusion prior to discharge within 24 h of ESD (1.8% vs 0%; p0.39), and 1 required rehospitalization and endoscopic intervention within 7 d to address an active bleed along the resection margin (1.8% vs 0%; p0.39). Overall, associated pathology was as follows: 5% had normal findings; 13.6% non-dysplastic Barrett’s esophagus (BE); 2.9% BE with indefinite dysplasia; 13.6% BE with low grade dysplasia; 20.7% BE with high grade dysplasia; 27.9% esophageal adenocarcinoma; 6.4% squamous cell carcinoma; and 10.0% had other findings, such as squamous dysplasia. Patients were on AP/AC therapy leading up to 42.9% of the procedures, including 5.7% on high dose aspirin, 2.9% clopidogrel, 6.4% warfarin, and 8.6% direct oral anticoagulants. SDD following esophageal ESD is safe and feasible. Additional prospective data will help establish more uniform criteria for low risk patients. Based on our experience, SDD can be considered in patients who are fit with ASA £2 and undergo smaller resections off AP/AC therapy.

Aspirin Dose and Treatment Outcomes in Kawasaki Disease: A Historical Control Study in Japan.

Aspirin has been used as a concomitant drug in the treatment of Kawasaki disease (KD). In recent years, there has been discussion concerning whether high-dose aspirin is appropriate for treatment in the acute phase of KD. We retrospectively investigated the incidence of coronary artery abnormalities (CAAs) and the antipyretic effect of 30 to 50 mg/kg/day aspirin, the minimum and the maximum approved doses in Japan. This was a single-center, non-randomized, retrospective, historical cohort study. Patients were routinely treated with 50 mg/kg/day aspirin (50-mg Group) between 2007 and April 2014, and with 30 mg/kg/day aspirin (30-mg Group) between May 2014 and 2016. All patients were given initial and, if necessary, subsequent intravenous immunoglobulin (IVIG) 2.0 g/kg. The primary endpoint was incidence of CAAs defined as a CA diameter with a Z score ≥2.5 at treatment week 4. The secondary endpoint was incidence of further treatment. Incidences were compared using inverse probability weighting analysis adjusting for age, sex, and risk scores. In 587 patients, there was no significant difference in incidence of CAAs (odds ratio in 30-mg Group 0.769, 95% confidence interval (CI): 0.537–1.101, p = 0.151). Risk of further treatment after the first IVIG in the 30-mg Group was significantly higher than that in the 50-mg Group (odds ratio 1.379, 95% CI: 1.051–1.811, p = 0.021). Although this study has some limitations, the findings suggest that aspirin 50 mg/kg/day may have no significant effect on improving incidence of CAAs compared with 30 mg/kg/day but may have a lower rate of further treatment.

High-Versus Low-Dose Aspirin in the Treatment of Kawasaki Disease

Research Article| April 01 2020 High-Versus Low-Dose Aspirin in the Treatment of Kawasaki Disease AAP Grand Rounds (2020) 43 (4): 44. https://doi.org/10.1542/gr.43-4-44 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation High-Versus Low-Dose Aspirin in the Treatment of Kawasaki Disease. AAP Grand Rounds April 2020; 43 (4): 44. https://doi.org/10.1542/gr.43-4-44 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: aspirin low dose, fever, immunoglobulins, intravenous, kawasaki's disease Source: Platt B, Belarski E, Manaloor J, et al. Comparison of risk of recrudescent fever in children with Kawasaki disease treated with intravenous immunoglobulin and low-dose vs high-dose aspirin. JAMA Netw Open. 2020; 3(1): e1918565; doi: https://doi.org/10.1001/jamanetworkopen.2019.18565Google Scholar Investigators from Indiana University, Indianapolis, IN, conducted a retrospective study to compare rates of recrudescent fever and coronary artery (CA) abnormalities in children treated with IV immunoglobulin (IVIG) and either low- or high-dose aspirin (ASA) for treatment of Kawasaki disease (KD). Study participants were children with KD treated within 10 days of symptom onset with 2 g/kg of IVIG and ASA at Riley’s Hospital for Children, Indianapolis, IN, between 2007 and 2018. Eligible children were identified using ICD-9 and ICD-10 codes; the medical records of eligible children were reviewed, and information was abstracted on demographics, symptoms before admission, clinical course during hospitalization and follow-up, echocardiography results, and dose of ASA. Initial ASA doses were categorized as low (<10 mg/kg/d) or high (>10 mg/kg/d). The primary outcome was recrudescent fever, defined as a rectal temperature >38.0°C or axillary temperature >37.5°C within 14 days of initial treatment that necessitated retreatment. Secondary outcomes were development of CA abnormalities and length of initial hospital stay. Outcomes in children treated with low- or high-dose ASA were compared using regression analyses after controlling for confounding variables. Subgroup analyses, limited to study patients with complete KD, also were conducted. Data were analyzed in 260 children with a median age of 2.5 years. There were 142 patients treated with low-dose ASA (median dose, 4.4 mg/kg/d), and 118 received high-dose ASA (median dose, 75.5 mg/kg/d). Most of the children in the low-dose group were treated before 2016, whereas most of those receiving high-dose ASA were treated after 2015. The 2 groups were similar for most other characteristics except that the percentage of children with incomplete KD was significantly higher among those in the high-dose group (44.1% vs 28.9% for those in the low-dose group; P = .01). Among those receiving low-dose ASA, the rate of recrudescent fever was 27.5% versus 26.0% in those receiving high-dose ASA. After adjusting for age <1 year and incomplete KD, the OR for recrudescent fever was 1.63 (95% CI, 0.89–2.97). Among the 167 study children with complete KD, the OR for recrudescent fever was 1.87 (95% CI, 0.82–4.23), when comparing the low- to high-dose groups. There was also no significant difference in rates of CA abnormalities between children in the low- and high-dose groups (7.4% and 9.4%, respectively; OR, 1.02; 95% CI, 0.55–1.87). The median length of hospital stay was 3 days for both groups (P = .27). The authors conclude that there was no difference in rates of recrudescent fever or CA abnormalities among children with KD treated with IVIG and either low- or high-dose ASA. Dr Spar has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.... You do not currently have access to this content.

What dose of aspirin should be used in the initial treatment of Kawasaki disease? A meta-analysis.

The use of IVIG plus high- or low-dose aspirin for the initial treatment of Kawasaki disease remains controversial. The aim of this study was to evaluate the efficacy of IVIG plus high-dose aspirin compared with IVIG plus low-dose aspirin in the treatment of Kawasaki disease. Studies related to aspirin therapy for Kawasaki disease were selected by searching the databases of Medline (PubMed), Embase and the Cochrane Library before March 2019. Statistical analyses were performed by using a Review Manager Software package and STATA v.15.1. Eight retrospective cohort studies, characterizing 12176 patients, were analysed. Overall, no significant difference was found in the incidence of coronary artery abnormalities between the high- and low-dose aspirin groups [relative risk (RR) 1.15; 95% CI: 0.93, 1.43; P = 0.19; random-effects model]. The patients treated with high-dose aspirin had slightly faster resolution of fever [mean difference (MD) -0.30; 95% CI: -0.58, -0.02; P = 0.04; random-effects model]. but the rates of IVIG resistance (RR, 1.26; 95% CI: 0.55, 2.92; P = 0.59; random-effects model) and days in hospital (MD, 0.22; 95% CI: -0.93, 1.37; P = 0.71; random-effects model) were similar between the two groups. Low-dose aspirin plus IVIG might be as effective as high-dose aspirin plus IVIG for the initial treatment of Kawasaki disease. Considering that high-dose aspirin may cause more adverse reactions than low-dose aspirin, low-dose aspirin plus IVIG should be recommended as the first-line therapy in the initial treatment of Kawasaki disease.

Effect of aspirin on microglia activation induced by Poly-IC and its regulatory mechanism

Objective To study whether aspirin has inhibitory effect on microglia activation induced by Poly-IC and its mechanism. Methods Microglia cell line BV2 were cultured in vitro to establish a Poly-IC stimulation-induced microglia cell immune activation model. The experiment groups were divided into control group (no treatment), model group (Poly-IC 10 μg/ml), high dose aspirin group (1 mmol/L aspirin), low dose aspirin group (0.1 mmol/L aspirin), high dose aspirin pretreatment group (Poly-IC 10 μg/ml + 1 mmol/L aspirin) and low dose aspirin pretreatment group (Poly-IC 10 μg/ml + 0.1 mmol/L aspirin). The phagocytosis ability of microglia cells, reactive oxygen species (ROS) and Iba1 protein expression were detected by using immunofluorescence method. The expression of the inflammatory cytokines Il-1β, Il-6, Il-10, TNF-α and cox-2 mRNA in microglia cells were detected by real-time quantitative PCR (RT-qPCR). Results Compared with the control group, the morphology of microglia cells in model group changed significantly, and the phagocytosis ability and production of reactive oxygen species (ROS) increased. At the meantime, the expression of Iba1 protein was strongly decreased. In the model group, The mRNA expressions of IL-1β(20.55±1.92), IL-6 (63.98±7.83), TNF-α (16.84±3.19), COX-2 (6.78±0.42) were higher than IL-1β(1.01±0.14), IL-6 (0.95±0.17), TNF-α (1.22±0.38), COX-2 (0.87±0.11) in the control group. (Il-1β (t=26.14), Il-6 (t=10.22), TNF-α (t=17.06) and COX-2 (t=37.07), all P<0.01). In the aspirin pretreatment group, the phagocytic ability of microglia cells was inhibited compared with the model group, and the production of reactive oxygen species (ROS) reduced. The expression of Iba1 protein was also partly recovered. Meanwhile, the effect of the high aspirin dose pretreatment group on pro-inflammatory factors IL-1β(9.95±0.52), IL-6 (39.64±6.89), TNF-α(1.57±0.42), COX-2 (2.47±0.14)were lower than those in the model group significantly.(IL-1β: t=14.18, IL-6: t=3.69, TNF-α: t=16.68, COX-2: t=27.03, all P<0.01). Conclusion Aspirin has an inhibitory effect on microglial activation induced by Poly-IC, which may be related with inhibiting the expression of inflammatory factors. Key words: Microglia cells; Poly-IC; Aspirin; Infection during pregnancy; Maternal immune activation

Equipoise in Management of Patients With Acute Symptomatic Carotid Stenosis (Hot Carotid).

To explore differences in antithrombotic management of patients with acutely symptomatic carotid stenosis ("hot carotid") awaiting revascularization with endarterectomy or stenting (CEA/CAS). We used a worldwide electronic survey with practice-related questions and clinical questions about 3 representative scenarios. Respondents chose their preferred antithrombotic regimen (1) in general, (2) if the patient was already on aspirin, or (3) had associated intraluminal thrombus (ILT) and identified clinical/imaging factors that increased or decreased their enthusiasm for additional antithrombotic agents. Responses among different groups were compared using multivariable logistic regression. We received 668 responses from 71 countries. The majority favored CT angiography (70.2%) to evaluate carotid stenosis, CEA (69.1%) over CAS, an aspirin-containing regimen (88.5%), and a clopidogrel-containing regimen (64.4%) if already on aspirin. Whereas diverse antithrombotic regimens were chosen, monotherapy was favored by 54.4%-70.6% of respondents across 3 scenarios. The preferred dual therapy was low-dose aspirin (75-100 mg) plus clopidogrel (22.2%) or high-dose aspirin (160-325 mg) plus clopidogrel if already on aspirin (12.2%). Respondents favoring CAS more often chose ≥2 agents (adjusted odds ratio [aOR] vs CEA: 2.00, 95% confidence interval 1.36-2.95, p = 0.001) or clopidogrel-containing regimens (aOR: 1.77, 1.16-2.70, p = 0.008). Regional differences included respondents from Europe less commonly choosing multiple agents if already on aspirin (aOR vs United States/Canada: 0.57, 0.35-0.93, p = 0.023), those from Asia more often favoring multiple agents (aOR: 1.95, 1.11-3.43, p = 0.020), vs those from the United States/Canada preferentially choosing heparin-containing regimens with ILT (aOR vs rest: 3.35, 2.23-5.03, p < 0.001). Factors increasing enthusiasm for ≥2 antithrombotics included multiple TIAs (57.2%), ILT (58.5%), and ulcerated plaque (57.4%); 56.3% identified MRI microbleeds as decreasing enthusiasm. Our results highlight the heterogeneous management and community equipoise surrounding optimal antithrombotic regimens for hot carotids.