Duration of high-dose aspirin therapy does not affect long-term coronary artery outcomes in Kawasaki disease

Migally, Karl; Braunlin, Elizabeth; Zhang, Lei; Binstadt, Bryce A.

doi:10.1038/pr.2018.44

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…In the study by Saulsbury et al, patients receiving IVIG were divided into 400 mg/kg for four consecutive days or a single infusion of 2 g/kg, and aspirin treatment was divided into 80-100 or 3-5 mg/kg/day (Saulsbury, 2002). The retrospective study of Wang et al divided aspirin into the following three groups: 20-29, 30-39, and 40-50 mg/kg/day (Wang et al, 2020 (Migally et al, 2018). Studies performed before the beginning or suggestion of IVIG treatment were excluded (Yokoyama et al, 1980;Koren et al, 1985b;Ichida et al, 1987).…”

Section: Resultsmentioning

confidence: 99%

Treatment of Kawasaki Disease: A Network Meta-Analysis of Four Dosage Regimens of Aspirin Combined With Recommended Intravenous Immunoglobulin

et al. 2021

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Aspirin was once believed to reduce the mortality of Kawasaki disease (KD) due to its effect on the thrombotic occlusion of coronary arteries. However, conflicting evidence has been found regarding aspirin treatment and its benefit in patients with acute KD. We compared the efficacy of different aspirin doses in acute KD. A literature search of PubMed, EMBASE, and Cochrane databases was conducted to identify studies comparing different doses of aspirin for acute KD. The primary outcome of interest was coronary artery lesions (CAL). We used random-effects network meta-analysis. Six retrospective studies, including 1944 patients receiving aspirin in doses of 0, 3–5, 30–50, or 80–100 mg/kg/day, were selected. The risks of CAL were not significantly different for the various doses of aspirin compared to the placebo: odds ratio (OR) was 1.10 [95% confidence interval (CI): 0.70–1.71] for patients with aspirin 3–5 mg/kg/day; OR = 1.23 (95% CI: 0.67–2.26) for aspirin 30–50 mg/kg/day, and OR = 1.59 (95% CI: 0.74, 3.421) for 80–100 mg/kg/day. The P-score ranged from 0.76 for placebo to 0.19 for aspirin 80–100 mg/kg/day. The different doses of aspirin exhibited no significant difference with regard to the efficacy of CAL or with the secondary outcomes of intravenous immunoglobulin resistance or hospital stays for acute KD. Therefore, we found that treatment without any aspirin is not inferior to other doses of aspirin and can also slightly reduce the risk of CAL.

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Section: Resultsmentioning

confidence: 99%

Treatment of Kawasaki Disease: A Network Meta-Analysis of Four Dosage Regimens of Aspirin Combined With Recommended Intravenous Immunoglobulin

et al. 2021

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“…This finding suggested that increasing the aspirin dose in the acute phase of KD may not needed. Furthermore, Migally et al [21] found that the duration of high-dose aspirin had no relationship with long-term prognosis of the coronary artery. This evidence suggests that high-, moderate-, and low-dose aspirin appear to have no significant difference in the prognosis of KD.…”

Section: Discussionmentioning

confidence: 99%

Effect of different doses of aspirin on the prognosis of Kawasaki disease

et al. 2020

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Background: Kawasaki disease (KD) is the leading cause of acquired heart disease in children, and is steadily increasing in prevalence in East Asia. KD is often complicated by coronary artery damage, including dilatation and/ or aneurysms. Aspirin is used with intravenous immunoglobulin (IVIG) to prevent coronary artery abnormalities in KD. However, the role and optimal dose of aspirin remain controversial. Identifying the dose of aspirin in the acute phase will facilitate development of a more appropriate treatment strategy in improving the outcome of KD. Methods: A total of 2369 patients with KD were retrospectively analyzed and divided into three groups according to the aspirin dose: 510 in group 1 (20-29 mg/kg/day), 1487 in group 2 (30-39 mg/kg/day), and 372 in group 3 (40-50 mg/kg/day). The differences in laboratory data, rate of IVIG resistance and coronary artery damage were compared among the groups. Results: There was no difference in the incidence of coronary artery aneurysms (CAAs) in group 1 compared with groups 2 and 3 (2 weeks of illness: 2.94% vs. 1.90% vs. 3.36%; 3-4 weeks of illness: 1.94% vs. 2.32% vs. 2.65%). The risk for developing CAA was not reduced at 2 weeks of illness onset in groups 2 and 3 compared with group 1 (adjusted OR = 1.05, 95% confidence interval: 0.34-3.18; aOR = 1.81, 95% CI: 0.42-7.83). Furthermore, the risk for developing CAA was not reduced at 3-4 weeks of illness onset in groups 2 and 3 (aOR = 2.63, 95% CI: 0.61-11.28; aOR = 0.52, 95% CI: 0.03-9.54). There was no significant difference in the rate of IVIG resistance among the groups. Platelet levels after IVIG treatment in group 1 were significantly lower than those in groups 2 and 3 (522.29 × 10 9 /L, 544.69 × 10 9 /L, and 557.77 × 10 9 /L, p = 0.013). C reactive protein of the 30-40 mg/kg*day group was slightly higher than the other two groups. (7.76, 8.00, and 7.01 mg/L, p = 0.028). Conclusions: Aspirin at the dose of 20-29 mg/kg/day dose not increase the risk of coronary artery damage and IVIG resistance compared with the dose of 30-50 mg/kg/day. This low dose may have a lower risk for a potential effect on liver function.

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“…The wide posology selection of aspirin for use in different diseases, which can range from about 50 mg to 3.6 g per day, provides much-needed information regarding the pharmacology, toxicity, and iron chelation efficacy of the ACMs [64][65][66][67][68][229][230][231][232][233]. The prospect of clinical testing of aspirin and ACM at the maximum range of posology for increasing iron excretion in thalassaemia and other iron-loaded diseases, similarly to the clinical studies previously carried out with 2,3-DHB, could further increase the range of clinical applications of aspirin and ACM in different diseases.…”

Section: Future Studies and Limitations On The Role Of Aspirin In Iro...mentioning

confidence: 99%

The Puzzle of Aspirin and Iron Deficiency: The Vital Missing Link of the Iron-Chelating Metabolites

Kontoghiorghes

2024

IJMS

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Acetylsalicylic acid or aspirin is the most commonly used drug in the world and is taken daily by millions of people. There is increasing evidence that chronic administration of low-dose aspirin of about 75–100 mg/day can cause iron deficiency anaemia (IDA) in the absence of major gastric bleeding; this is found in a large number of about 20% otherwise healthy elderly (>65 years) individuals. The mechanisms of the cause of IDA in this category of individuals are still largely unknown. Evidence is presented suggesting that a likely cause of IDA in this category of aspirin users is the chelation activity and increased excretion of iron caused by aspirin chelating metabolites (ACMs). It is estimated that 90% of oral aspirin is metabolized into about 70% of the ACMs salicyluric acid, salicylic acid, 2,5-dihydroxybenzoic acid, and 2,3-dihydroxybenzoic acid. All ACMs have a high affinity for binding iron and ability to mobilize iron from different iron pools, causing an overall net increase in iron excretion and altering iron balance. Interestingly, 2,3-dihydroxybenzoic acid has been previously tested in iron-loaded thalassaemia patients, leading to substantial increases in iron excretion. The daily administration of low-dose aspirin for long-term periods is likely to enhance the overall iron excretion in small increments each time due to the combined iron mobilization effect of the ACM. In particular, IDA is likely to occur mainly in populations such as elderly vegetarian adults with meals low in iron content. Furthermore, IDA may be exacerbated by the combinations of ACM with other dietary components, which can prevent iron absorption and enhance iron excretion. Overall, aspirin is acting as a chelating pro-drug similar to dexrazoxane, and the ACM as combination chelation therapy. Iron balance, pharmacological, and other studies on the interaction of iron and aspirin, as well as ACM, are likely to shed more light on the mechanism of IDA. Similar mechanisms of iron chelation through ACM may also be implicated in patient improvements observed in cancer, neurodegenerative, and other disease categories when treated long-term with daily aspirin. In particular, the role of aspirin and ACM in iron metabolism and free radical pathology includes ferroptosis, and may identify other missing links in the therapeutic effects of aspirin in many more diseases. It is suggested that aspirin is the first non-chelating drug described to cause IDA through its ACM metabolites. The therapeutic, pharmacological, toxicological and other implications of aspirin are incomplete without taking into consideration the iron binding and other effects of the ACM.

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Duration of high-dose aspirin therapy does not affect long-term coronary artery outcomes in Kawasaki disease

Cited by 5 publications

References 27 publications

Treatment of Kawasaki Disease: A Network Meta-Analysis of Four Dosage Regimens of Aspirin Combined With Recommended Intravenous Immunoglobulin

Treatment of Kawasaki Disease: A Network Meta-Analysis of Four Dosage Regimens of Aspirin Combined With Recommended Intravenous Immunoglobulin

Effect of different doses of aspirin on the prognosis of Kawasaki disease

The Puzzle of Aspirin and Iron Deficiency: The Vital Missing Link of the Iron-Chelating Metabolites

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