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

Abstract Objective 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. Methods 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. Results Eight retrospective cohort studies, characterizing 12 176 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. Conclusion 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.

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Dose-dependent roles of aspirin and other non-steroidal anti-inflammatory drugs in abnormal bone remodeling and skeletal regeneration

Cell & Bioscience ◽

10.1186/s13578-019-0369-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Yong Xie ◽

Meng Pan ◽

Yanpan Gao ◽

Licheng Zhang ◽

Wei Ge ◽

...

Keyword(s):

Bone Formation ◽

Bone Remodeling ◽

Low Dose ◽

High Dose ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Dose Dependent ◽

High Dose Aspirin

AbstractThe failure of remodeling process that constantly regenerates effete, aged bone is highly associated with bone nonunion and degenerative bone diseases. Numerous studies have demonstrated that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) activate cytokines and mediators on osteoclasts, osteoblasts and their constituent progenitor cells located around the remodeling area. These cells contribute to a complex metabolic scenario, resulting in degradative or synthetic functions for bone mineral tissues. The spatiotemporal effects of aspirin and NSAIDs in the bone remodeling are controversial according the specific therapeutic doses used for different clinical conditions. Herein, we review in vitro, in vivo, and clinical studies on the dose-dependent roles of aspirin and NSAIDs in bone remodeling. Our results show that low-dose aspirin (< 100 μg/mL), which is widely recommended for prevention of thrombosis, is very likely to be benefit for maintaining bone mass and qualities by activation of osteoblastic bone formation and inhibition of osteoclast activities via cyclooxygenase-independent manner. While, the roles of high-dose aspirin (150–300 μg/mL) and other NSAIDs in bone self-regeneration and fracture-healing process are difficult to elucidate owing to their dual effects on osteoclast activity and bone formation of osteoblast. In conclusion, this study highlighted the potential clinical applications of low-dose aspirin in abnormal bone remodeling as well as the risks of high-dose aspirin and other NSAIDs for relieving pain and anti-inflammation in fractures and orthopedic operations.

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Modification of the Outcome of Coronary Thrombo-Embolism by Low and High-Dose Aspirin

10.1055/s-0039-1684407 ◽

1979 ◽

Author(s):

S. Moore ◽

L.W. Belbeck ◽

S.A. Pineau

Keyword(s):

Low Dose ◽

Myocardial Damage ◽

High Dose ◽

Aluminum Wire ◽

Ischaemic Damage ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Group 3 ◽

High Dose Aspirin ◽

Heart Foundation

Previous work in this laboratory has shown that an occlusive thrombus (O.T.) induced. the left anterior descending coronary artery (L.A.D.) of dogs, by the placement of a segment of magnesium-aluminum wire (M.A.W.) in the lumen of the artery, is associated with the development of full thickness infarct (F.T.I.). Incomplete (mural) thrombus is associated with focal areas of ischaemic damage, mainly sub-endocardial, in the myocardium of the antero-lateral left ventricle. A 1.0 cm. length of M.A.W., shaped in the form of a tennis racquet, was placed by cardiac catheterization in the proximal L.A.D. of 30 mongrel dogs. Ten dogs received low dose aspirin (L.D.A.); (14 or 29 mgm/Kg daily in a single dose). Ten dogs received high dose aspirin (H.D.A.); (100 mgm/Kg daily in divided doses). Treatment was begun one day before operation and continued until death or killing. Ten control dogs received no drug. All control dogs died within 3 days of operation. Five had O.T. and F.T.I. The remainder showed focal ischaemic myocardial damage. None of the L.D.A. group died. At autopsy 3 or 4 days after operation, none had O.T. or F.T.I. In the H.D.A. group 3 died; 4 had O.T. and F.T.I. Thus L.D.A. provided significant protection from death, O.T., and F.T.I. H.D.A. provided some (P <0.005) but less protection from death but did not significantly affect the incidence of O.T. or F.T.I. Supported by Ontario Heart Foundation Grant T15-7.

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P.067 A worldwide survey of physician approaches to patients with acutely symptomatic carotid stenosis (“hot carotid”)

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2021.347 ◽

2021 ◽

Vol 48 (s3) ◽

pp. S38-S38

Author(s):

A Ganesh ◽

G Jewett ◽

DJ Campbell ◽

R Singh ◽

A Al-Sultan ◽

...

Keyword(s):

Carotid Stenosis ◽

Low Dose ◽

Dual Therapy ◽

High Dose ◽

Symptomatic Carotid ◽

Dose Aspirin ◽

Symptomatic Carotid Stenosis ◽

Low Dose Aspirin ◽

Recurrent Strokes ◽

High Dose Aspirin

Background: Patients with acutely symptomatic carotid stenosis (“hot carotid”) have high up-front risk of recurrent strokes. Uncertainties remain regarding optimal anti-thrombotic management, particularly while awaiting revascularization with endarterectomy or stenting (CEA/CAS). Methods: We administered a worldwide electronic survey through Neurology: Clinical Practice. Respondents chose their preferred antithrombotic regimen (1) in a general case of acutely symptomatic carotid stenosis, (2) if the patient was already on aspirin, or (3) had associated intraluminal thrombus(ILT). Responses among different groups were compared using multivariable logistic regression. Results: We received 668 responses from 71 countries. Most respondents favoured CEA(69.1%) over CAS, an aspirin-containing regimen(88.5%), and a clopidogrel-containing regimen(64.4%) if already on aspirin. Monotherapy was favoured by 54.4-70.6% across scenarios. The preferred dual therapy was low-dose aspirin(75-100mg) plus clopidogrel(22.2%), or high-dose aspirin(160-325mg) plus clopidogrel if already on aspirin(12.2%). Respondents favouring CAS more often chose ≥2 agents (adjusted odds-ratio[aOR] vs CEA: 2.00, 95%CI 1.36-2.95,p=0.001) or clopidogrel-containing regimens (aOR:1.77,1.16-2.70,p=0.008). Respondents from Europe less commonly chose multiple agents (aOR vs United States/Canada: 0.57,0.35–0.93,p=0.023) while those from Asia more often favored multi-agent regimens (aOR:1.95,1.11–3.43,p=0.020). Conclusions: Our results highlight the heterogeneous anti-thrombotic management of hot carotids. Future trials should likely include high-dose aspirin monotherapy or low-dose aspirin/clopidogrel dual-therapy as a comparator arm to stimulate enrolment.

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Comparison of Risk of Recrudescent Fever in Children With Kawasaki Disease Treated With Intravenous Immunoglobulin and Low-Dose vs High-Dose Aspirin

JAMA Network Open ◽

10.1001/jamanetworkopen.2019.18565 ◽

2020 ◽

Vol 3 (1) ◽

pp. e1918565 ◽

Cited By ~ 3

Author(s):

Brooks Platt ◽

Emily Belarski ◽

John Manaloor ◽

Susan Ofner ◽

Aaron E. Carroll ◽

...

Keyword(s):

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Low Dose ◽

High Dose ◽

Dose Aspirin ◽

High Dose Aspirin

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Comparison of High-Dose versus Low-Dose Aspirin in the Management of Kawasaki Disease

The Indian Journal of Pediatrics ◽

10.1007/s12098-014-1437-0 ◽

2014 ◽

Vol 81 (12) ◽

pp. 1403-1403 ◽

Cited By ~ 8

Author(s):

Aliakbar Rahbarimanesh ◽

Mozhgan Taghavi-Goodarzi ◽

Payam Mohammadinejad ◽

Javad Zoughi ◽

Jalalaldin Amiri ◽

...

Keyword(s):

Kawasaki Disease ◽

Low Dose ◽

High Dose ◽

Dose Aspirin ◽

Low Dose Aspirin

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High-dose aspirin in addition to daily low-dose aspirin decreases platelet activation in patients before and after percutaneous coronary intervention

Thrombosis Research ◽

10.1016/s0049-3848(02)00040-3 ◽

2002 ◽

Vol 105 (5) ◽

pp. 385-390 ◽

Cited By ~ 15

Author(s):

Jurriën M ten Berg ◽

Wim B.M Gerritsen ◽

Fred J.L.M Haas ◽

Hans C Kelder ◽

Freek W.A Verheugt ◽

...

Keyword(s):

Percutaneous Coronary Intervention ◽

Platelet Activation ◽

Low Dose ◽

Coronary Intervention ◽

High Dose ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Percutaneous Coronary ◽

Before And After ◽

High Dose Aspirin

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High-Dose, but Not Low-Dose, Aspirin Impairs Anticontractile Effect of Ticagrelor following ADP Stimulation in Rat Tail Artery Smooth Muscle Cells

BioMed Research International ◽

10.1155/2013/928271 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Grzegorz Grześk ◽

Marek Kozinski ◽

Udaya S. Tantry ◽

Michal Wicinski ◽

Tomasz Fabiszak ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Low Dose ◽

Muscle Cells ◽

High Dose ◽

Maximal Effect ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Rat Tail ◽

High Dose Aspirin

Objective.To compare effects of low- versus high-dose aspirin coadministered with ticagrelor on the reactivity of vascular smooth muscle cells (VSMCs).Methods.Wistar rats were orally administered ticagrelor (10 mg/kg) and/or aspirin (2 or 10 mg/kg) (n=7per each of 4 groups) or placebo (n=9) 12 and 2 hours before experiments. Anticontractile effects of ticagrelor were assessed in perfusion solution containing ticagrelor (1 μM/L). Changes in perfusion pressure proportional to the degree of adenosine diphosphate analogue- (2-MeS-ADP-) and phenylephrine-induced constriction of rat tail arteries were evaluated.Results.Pretreatment with high- but not low-dose aspirin enhanced the reactivity of VSMCs only in endothelium-lined vessels. Suppression of 2-MeS-ADP-induced VSMC contraction by ticagrelor observed in arteries with and without endothelium was maintained in endothelialized arteries pretreated only with low-dose aspirin. For endothelium-denuded vessels and low-dose aspirin we observed a significant reduction of the maximal effect of ticagrelor with no rightward shift of the concentration-response curve for phenylephrine. With high-dose aspirin pretreatment ticagrelor exerted no anticontractile effect.Conclusion.High-dose, but not low-dose, aspirin impairs the anticontractile effect of ticagrelor on ADP-induced VSMC contraction in the rat model. Both the clinical significance and detailed underlying mechanism of our findings require further investigation.

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Rapid and Selective Inhibition of Platelet Aggregation and Thromboxane Formation by Intravenous Low Dose Aspirin in Man

Clinical Science ◽

10.1042/cs0840517 ◽

1993 ◽

Vol 84 (5) ◽

pp. 517-524 ◽

Cited By ~ 24

Author(s):

Rainer H. Böger ◽

Stefanie M. Bode-Böger ◽

Frank M. Gutzki ◽

Dimitrios Tsikas ◽

Hans-P. Weskott ◽

...

Keyword(s):

Platelet Aggregation ◽

Low Dose ◽

Thromboxane A2 ◽

Systemic Circulation ◽

High Dose ◽

Dose Aspirin ◽

Major Urinary Metabolite ◽

Low Dose Aspirin ◽

High Dose Aspirin ◽

Platelet Thromboxane

1. One of the major problems in the clinical use of low dose aspirin for the prevention of vascular occlusion is that it takes about 3–5 days to become effective, a time too long for patients with unstable angina or coronary thrombolysis. Intravenous aspirin may be expected to exert a more rapid effect, but its influence on endothelial prostacyclin synthesis is uncertain. 2. In a single-blind, randomized, prospective study, we compared the effects of a single intravenous low dose (50 mg) or high dose (500 mg) of aspirin or placebo infused over a 60 min period on platelet aggregation, platelet thromboxane A2 production and whole-body prostanoid synthesis in 10 healthy male subjects by gas chromatography-tandem mass spectrometry. 3. Before the study, blood flow rates in the basilic and subclavian veins were determined by sonographic colour velocity imaging; the infusion rate for low dose aspirin was calculated to avoid biologically effective plasma levels of aspirin in the systemic circulation. 4. Platelet aggregation induced by 1 mmol/l arachidonic acid was similarly inhibited by >85% within 30 min after the start of the infusion of high dose or low dose aspirin, respectively, and remained suppressed for 24 h. Platelet thromboxane A2 release declined gradually after low dose aspirin, reaching a minimum of 93% inhibition after 60 min. High dose aspirin suppressed platelet thromboxane A2 release to below the detection limit after 10 min. 5. Urinary excretion of the major urinary metabolite of thromboxane A2 (2,3-dinor-thromboxane B2) was equally suppressed by both dosages of aspirin [no significant difference between high dose (−83.2%) and low dose (−67.4%)]. The urinary excretion of the major urinary metabolite of prostacyclin (2,3-dinor-6-keto-prostaglandin F1α) and of prostaglandin E2 was also markedly decreased, by 79.2% and 63.5%, respectively, by high dose aspirin, whereas low dose aspirin suppressed 2,3-dinor-6-keto-prostaglandin F1α excretion significantly less (−30.3%; P <0.02), and had no inhibitory effect at all on prostaglandin E2 excretion, indicating that after intravenous low dose aspirin no biologically active acetylsalicylate was present in the systemic circulation. 6. These data show that intravenous low dose aspirin can inhibit platelet aggregation and thromboxane B2 synthesis within less than 2 h while sparing systemic cyclo-oxygenase activity. Partial inhibition of prostacyclin formation seems to be an unavoidable consequence of effective inhibition of platelet cyclooxygenase by aspirin.

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Modification of the Outcome of Coronary Thrombo-Embolism by Low and High-Dose Aspirin

10.1055/s-0038-1665678 ◽

1979 ◽

Author(s):

S Moore ◽

L Belbeck ◽

S Pineau

Keyword(s):

Low Dose ◽

Myocardial Damage ◽

High Dose ◽

Aluminum Wire ◽

Ischaemic Damage ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Group 3 ◽

High Dose Aspirin ◽

Heart Foundation

Previous work in this laboratory has shown that an occlusive thrombus (O.T.) induced in the left anterior descending coronary artery (L.A.D.) of dogs, by the placement of a segment of magnesium-aluminum wire (M.A.W.) in the lumen of the artery, is associated, with the development of full thickness infarct (F.T.I.). Incomplete (mural) thrombus is associated with focal areas of ischaemic damage, mainly sub-endocardial, in the myocardium of the antero-lateral left ventricle. A 1.0 cm. length of M.A.W., shaped in the form of a tennis racquet, was placed by cardiac catheterization in the proximal L.A.D. of 30 mongrel dogs. Ten dogs received low dose aspirin (L.D.A.); (14 or 29 mgm/Kg daily in a single dose). Ten dogs received high dose aspirin (H.D.A.); (100 mgm/Kg daily in divided doses). Treatment was begun one day before operation and continued until death or killing. Ten control dogs received no drug. All control dogs died within 3 days of operation. Five had O.T. and F.T.I. The remainder showed focal ischaemic myocardial damage. None of the L.D.A. group died. At autopsy 3 or 4 days after operation, none had O.T. or F.T.I. In the H.D.A. group 3 died; 4 had O.T. and F.T.I. Thus L.D.A. provided significant protection from death, O.T., and F.T.I. H.D.A. provided some (P<0.005) but less protection from death but did not significantly affect the incidence of O.T. or F.T.I Supported by Ontario Heart Foundation Grant T15-7.

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