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

Eur J Pediatr. 2024 Nov;183(11):4817-4825. doi: 10.1007/s00431-024-05765-3. Epub 2024 Sep 6.

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.

Keywords: Angiotensin II; Coronary artery aneurysm; Kawasaki disease; Regression.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors* / therapeutic use
  • Child
  • Child, Preschool
  • Coronary Aneurysm* / drug therapy
  • Coronary Aneurysm* / etiology
  • Female
  • Humans
  • Infant
  • Japan
  • Male
  • Mucocutaneous Lymph Node Syndrome* / complications
  • Mucocutaneous Lymph Node Syndrome* / drug therapy
  • Prospective Studies
  • Renin-Angiotensin System / drug effects
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin Receptor Antagonists
  • Angiotensin II Type 1 Receptor Blockers