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06.09.2024 | RESEARCH

Regression effect of renin–angiotensin–aldosterone system inhibitors on Kawasaki disease patients with coronary artery aneurysm: a prospective, observational study

verfasst von: Eisuke Suganuma, Masaru Miura, Yutaro Koyama, Tohru Kobayashi, Tetsuji Kaneko, Tatsunori Hokosaki, Fujito Numano, Kenji Furuno, Junko Shiono, Shigeto Fuse, Ryuji Fukazawa, Yoshihide Mitani

Erschienen in: European Journal of Pediatrics | Ausgabe 11/2024

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Abstract

Purpose

This study is to investigate whether angiotensin type 1 receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEis) can regress coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD).

Methods

This multicenter, prospective, observational study was conducted at 53 institutions throughout Japan. We enrolled patients who were diagnosed with KD after January 2015 and had a medium or large CAA (maximum luminal diameter ≥ 4 mm or z score ≥ + 5) 30 days or later after KD onset.

Results

Of the 209 patients, 47 (22%) were taking ARBs/ ACEis. Compared with those in the non-ARB/ACEi group, the baseline CAA diameter was significantly greater (6.7 mm vs. 5.5 mm, p < 0.01), and bilateral CAA (70% vs. 59%, p = 0.01) and giant CAA (32% vs. 20%, p = 0.08) were more frequently observed in the ARB/ACEi group. Although the overall regression rates did not differ between the groups (67% vs. 65%), the regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group (36% vs. 23%). Multivariate Cox regression analysis after adjustment for other clinical variables suggested that ARBs/ACEis may be a factor in CAA regression (hazard ratio [HR]: 1.5, 95% confidence interval [CI]: 0.91–2.46).

Conclusions

Although ARBs/ ACEis were used more frequently in patients with severe CAA, these patients had similar CAA regression rates to patients not taking ARBs/ACEis. ARBs/ACEis may be beneficial agents aimed at inducing CAA regression in KD patients.

What is Known:

• Large CAAs are less likely to regress and are always at risk of life-threatening cardiac events.

• Moderate CAA, age less than 1 year, and female sex have been reported to be factors that promote the regression of CAA.

What is New:

• Although ARBs/ACEis were used more frequently in patients with severe CAA, these patients had a similar rate of CAA regression to patients who did not take ARBs/ACEis.

• The regression rates of giant CAA were approximately 1.6 times greater in the ARB/ACEi group than in the non-ARB/ACEi group.

Fukazawa R, Kobayashi T, Mikami M, Saji T, Hamaoka K, Kato H, Suzuki H, Tsuda E, Ayusawa M, Miura M et al (2017) Nationwide survey of patients with giant coronary aneurysm secondary to Kawasaki disease 1999–2010 in Japan. Circ J 82:239–246. https://doi.org/10.1253/circj.CJ-17-0433CrossRefPubMed

Miura M, Kobayashi T, Kaneko T, Ayusawa M, Fukazawa R, Fukushima N, Fuse S, Hamaoka K, Hirono K, Kato T et al (2018) Association of severity of coronary artery aneurysms in patients with Kawasaki disease and risk of later coronary events. JAMA Pediatr 172(5):e180030. https://doi.org/10.1001/jamapediatrics.2018.0030CrossRefPubMedPubMedCentral

Koyama Y, Miura M, Kobayashi T, Hokosaki T, Suganuma E, Numano F, Furuno K, Shiono J, Ebata R, Fuse S et al (2023) A registry study of Kawasaki disease patients with coronary artery aneurysms (KIDCAR): a report on a multicenter prospective registry study three years after commencement. Eur J Pediatr 182:633–640. https://doi.org/10.1007/s00431-022-04719-xCrossRefPubMed

Kato H, Sugimura T, Akagi T, Sato N, Hashino K, Maeno Y, Kazue T, Eto G, Yamakawa R (1996) Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients. Circulation 94:1379–1385. https://doi.org/10.1161/01.CIR.94.6.1379CrossRefPubMed

Friedman KG, Gauvreau K, Hamaoka-Okamoto A, Tang A, Berry E, Tremoulet AH, Mahavadi VS, Baker A, deFerranti SD, Fulton DR et al (2016) Coronary artery aneurysms in Kawasaki disease: Risk factors for progressive disease and adverse cardiac events in the US population. J Am Heart Assoc 5:e003289. https://doi.org/10.1161/JAHA.116.003289CrossRefPubMedPubMedCentral

Kato T, Miura M, Kobayashi T, Kaneko T, Fukushima N, Suda K, Maeda J, Shimoyama S, Shiono J, Hirono K et al (2023) Analysis of coronary arterial aneurysm regression in patients with Kawasaki disease by aneurysm severity: factors associated with regression. J Am Heart Assoc 12:e022417. https://doi.org/10.1161/JAHA.121.022417CrossRefPubMedPubMedCentral

Lévy BI, Mourad JJ (2022) Renin angiotensin blockers and cardiac protection: from basis to clinical trials. Am J Hypertens 35:293–302. https://doi.org/10.1093/ajh/hpac018CrossRefPubMed

McMurray J, Solomon S, Pieper K, Reed S, Rouleau J, Velazquez E, White H, Howlett J, Swedberg K, Maggioni A et al (2006) The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). J Am Coll Cardiol 47:726–733. https://doi.org/10.1016/j.jacc.2005.09.055CrossRefPubMed

Suganuma E, Babaev VR, Motojima M, Zuo Y, Ayabe N, Fogo AB, Ichikawa I, Linton MF, Fazio S, Kon V (2007) Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques. J Am Soc Nephrol 18:2311–2319. https://doi.org/10.1681/ASN.2006090967CrossRefPubMed

10.

Hornig B, Landmesser U, Kohler C, Ahlersmann D, Spiekermann S, Christoph A, Tatge H, Drexler H (2001) Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of superoxide dismutase. Circulation 103:799–805. https://doi.org/10.1161/01.CIR.103.6.799CrossRefPubMed

11.

Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C et al (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312:117–121. https://doi.org/10.1126/science.1124287CrossRefPubMedPubMedCentral

12.

Shimizu C, Jain S, Davila S, Hibberd ML, Lin KO, Molkara D, Frazer JR, Sun S, Baker AL, Newburger JW et al (2011) Transforming growth factor-signaling pathway in patients with Kawasaki disease. Circ Cardiovasc Genet 4:16–25. https://doi.org/10.1161/CIRCGENETICS.110.940858CrossRefPubMed

13.

Suganuma E, Niimura F, Matsuda S, Ukawa T, Nakamura H, Sekine K, Kato M, Aiba Y, Koga Y, Hayashi K et al (2017) Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease. Pediatr Res 81:593–600. https://doi.org/10.1038/pr.2016.266CrossRefPubMed

14.

Kobayashi T, Fuse S, Sakamoto N, Mikami M, Ogawa S, Hamaoka K, Arakaki Y, Nakamura T, Nagasawa H, Kato T et al (2016) A new Z score curve of the coronary arterial internal diameter using the lambda-mu-sigma method in a pediatric population. J Am Soc Echocardiogr 29:794–801. https://doi.org/10.1016/j.echo.2016.03.017CrossRefPubMed

15.

Friedman KG, Gauvreau K, Baker A, Son MB, Sundel R, Dionne A, Giorgio T, De Ferranti S (2021) Newburger JW (2021) Primary adjunctive corticosteroid therapy is associated with improved outcomes for patients with Kawasaki disease with coronary artery aneurysms at diagnosis. Arch Dis Child 106:247–252. https://doi.org/10.1136/archdischild-2020-319810CrossRefPubMed

16.

Takahashi M, Mason W, Lewis A (1987) Regression of coronary aneurysms in patients with Kawasaki syndrome. Circulation 75:387–394. https://doi.org/10.1161/01.CIR.75.2.387CrossRefPubMed

17.

Akagi T, Rose V (1992) Bensen LN Freedom RM (1992) Outcome of coronary artery aneurysms after Kawasaki disease. J Pediatr 121:689–694. https://doi.org/10.1016/S0022-3476(05)81894-3CrossRefPubMed

18.

Nagatomo Y, Muneuchi J, Nakashima Y, Nanishi E, Shirozu H, Watanabe M, Uike K, Nagata H, Hirata Y, Yamamura K et al (2018) Effective infliximab therapy for the early regression of coronary artery aneurysm in Kawasaki disease. Int J Cardiol 271:317–321. https://doi.org/10.1016/j.ijcard.2018.04.062CrossRefPubMed

19.

Portman MA, Dahdah NS, Slee A, Olson AK, Choueiter NF, Soriano BD, Buddhe S, Altman CA (2019) Etanercept with IVIg for acute Kawasaki disease: a randomized controlled trial. Pediatrics 143:e20183675. https://doi.org/10.1542/peds.2018-3675CrossRefPubMed

20.

Sagiv E, Slee A, Buffone A, Choueiter NF, Dahdah NS, Portman MA (2023) Etanercept with IVIg for acute Kawasaki disease: a long-term follow-up on the EATAK trial. Cardiol Young 33:613–618. https://doi.org/10.1017/S1047951122001470CrossRefPubMed

21.

Takahashi K, Oharaseki T, Yokouchi Y, Yamada H, Shibuya K, Naoe S (2012) A half-century of autopsy results–incidence of pediatric vasculitis syndromes, especially Kawasaki disease. Circ J 76:964–970. https://doi.org/10.1253/circj.CJ-11-0928CrossRefPubMed

22.

Schmieder RE, Hilgers KF, Schlaich MP, Schmidt BM (2007) Renin-angiotensin system and cardiovascular risk. Lancet 369:1208–1219. https://doi.org/10.1016/S0140-6736(07)60242-6CrossRefPubMed

23.

Fukazawa R, Sonobe T, Hamamoto K, Hamaoka K, Sakata K, Asano T, Imai T, Kamisago M, Ohkubo T, Uchikoba Y et al (2004) Possible synergic effect of angiotensin-I converting enzyme gene insertion/deletion polymorphism and angiotensin-II type-1 receptor 1166A/C gene polymorphism on ischemic heart disease in patients with Kawasaki disease. Pediatr Res 56:597–601. https://doi.org/10.1203/01.PDR.0000139426.16381.C8CrossRefPubMed

24.

Gan Y, Feng Y, Zhou X, Li H, Wang G, Aini M, Shu J, Tu D (2023) Serum levels of angiotensin-converting enzyme 2 in children with Kawasaki disease. Clin Exp Med 23:1325–1330. https://doi.org/10.1007/s10238-022-00933-xCrossRefPubMed

Titel: Regression effect of renin–angiotensin–aldosterone system inhibitors on Kawasaki disease patients with coronary artery aneurysm: a prospective, observational study
verfasst von: Eisuke Suganuma
Masaru Miura
Yutaro Koyama
Tohru Kobayashi
Tetsuji Kaneko
Tatsunori Hokosaki
Fujito Numano
Kenji Furuno
Junko Shiono
Shigeto Fuse
Ryuji Fukazawa
Yoshihide Mitani
Publikationsdatum: 06.09.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Pediatrics / Ausgabe 11/2024
Print ISSN: 0340-6199
Elektronische ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-024-05765-3

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Regression effect of renin–angiotensin–aldosterone system inhibitors on Kawasaki disease patients with coronary artery aneurysm: a prospective, observational study