Standard therapy, consisting of intravenous immunoglobulin and aspirin, reduces, but does not eliminate, coronary artery aneurysms (CAAs) in patients with Kawasaki disease. Large CAAs can persist or undergo varying degrees of regression. The treatment of large CAAs using abciximab has been associated with short-term regression; however, longer term data are unavailable. We sought to obtain longer term follow-up data regarding the changes in the diameters of large CAAs in patients receiving both abciximab and standard therapy and to compare these changes to those of a similar group receiving standard therapy alone. All patients with Kawasaki disease and large CAAs (diameter >5 mm or Z score >10) treated from 1986 to 2007 were identified and divided into 2 groups. The abciximab group received abciximab plus standard therapy and the no-abciximab group received standard therapy alone. The maximum diameters of the proximal right and left anterior descending CAAs were obtained from echocardiograms. The Z scores were calculated for 3 points: the acute/subacute phase (<8 weeks) and at 1 and 3 to 5 years of follow-up. The patients in the abciximab (n = 11) and no-abciximab (n = 7) groups were similar in age, interval to treatment, gender, and largest CAA Z score at diagnosis (19.6 ± 6.2 vs 25.8 ± 9.5, p = 0.11). The change in CAA Z score was similar between the 2 groups at 1 year (p = 0.99). At 3 to 5 years of follow-up, compared to baseline, the abciximab group had a greater decrease in the CAA Z score than did the no-abciximab group (−14.0 ± 4.0 vs −8.2 ± 5.9, p = 0.04). In conclusion, abciximab treatment might be associated with vascular remodeling in patients with large CAAs.
Kawasaki disease (KD) is an acute vasculitis of unknown etiology and is the leading cause of acquired heart disease in children in the United States. Although the vasculitis is generalized, the disease has a predilection for the coronary arteries. The long-term morbidity and mortality has been associated with the development of coronary artery aneurysms (CAAs), which occur in about 20% of untreated patients during the subacute phase. Because the etiology of the disease is unknown, the treatment is nonspecific and has been directed toward modulation of the inflammatory response and inhibition of platelet aggregation. Standard therapy, consisting of intravenous immunoglobulin plus high-dose aspirin in the acute phase, has been shown to decrease the incidence of CAAs to approximately 5%. Children who develop large CAAs are at the greatest risk of long-term complications such as thrombus formation and the development of coronary artery stenosis, with associated ischemic heart disease. Abciximab is a human-murine monoclonal antibody fragment that binds to the platelet glycoprotein IIb/IIIa receptor and has been shown to reduce thrombotic complications and promote vascular remodeling in adults with acute coronary syndromes. Although abciximab for the acute treatment of patients with KD and large CAAs has been associated with early regression of these CAAs, no data are available regarding the coronary artery changes in the largest CAA during longer periods. The purposes of the present study were to obtain longer term follow-up data regarding the changes in the large CAA diameter in patients treated with abciximab in addition to standard therapy and to compare these changes to those occurring in a similarly affected group treated with standard therapy alone.
Methods
The Pediatric Cardiology Database was reviewed to identify all patients with large CAAs, with a diameter >5 mm or a Z score >10, who had been treated from 1986 to 2007. The patients were divided into 2 groups according to the treatment they had received during the acute phase of their illness. The abciximab group received abciximab plus standard therapy (intravenous gammaglobulin [IVIG], 2 g/kg as a single dose, and high-dose aspirin, 80 to 100 mg/kg/day), and the no-abciximab group received standard therapy alone. IVIG was given within 24 hours of the diagnosis. After discussion of the off-label use with the parent, abciximab was administered intravenously, with a loading bolus dose of 0.25 mg/kg followed by an infusion of 0.125 μg/kg/min within 12 hours 24 to 48 hours after the IVIG infusions were completed. The institutional review board approved the present retrospective study with a waiver of consent.
The echocardiogram reports were reviewed for coronary artery size. The Z scores (for body surface area) were calculated for the maximum diameter of the CAA of the proximal right and/or left anterior descending coronary artery during the acute/subacute phase (<8 weeks) and at 1 and 3 to 5 years of follow-up. For those with multivessel involvement, the largest CAA Z score was used for the analysis. The data are expressed as the mean ± SD. Paired t tests were used for the within-group comparisons, and unpaired t tests or the Mann-Whitney rank sum test, as appropriate, were used to compare the changes in coronary artery Z scores between the 2 groups at 3 intervals: (1) from baseline to 1 year of follow-up; (2) from 1 year to 3 to 5 years of follow-up; and (3) from baseline to 3 to 5 years of follow-up. Statistical significance was defined as p <0.05. The charts were reviewed for the occurrence of acute myocardial infarction, cardiac transplantation, or death. Statistical analysis was performed using Sigma Plot, version 11.0 (SYSTAT, Chicago, Illinois).
Results
Large CAAs were identified in 18 patients. Of these 18 patients, 11 had received abciximab plus standard therapy and 7 had received standard therapy alone. The groups were similar in age and the duration of fever before treatment ( Table 1 ). Males predominated in both groups (91% in the abciximab group and 71% in the no-abciximab group). The abciximab group had been treated more recently (since 1997) than the no-abciximab group (1986 to 1997). The largest CAA Z scores at diagnosis were not signficantly different statistically between the 2 groups (19.6 ± 6.2 in the abciximab group vs 25.8 ± 9.5 in the no-abciximab group, p = 0.11). Data were available for 9 abciximab patients (82%) and all 7 of the no-abciximab patients (100%) at 1 year of follow-up and for 10 abciximab patients (91%) and 5 no-abciximab patients (71%) at 3 to 5 years of follow-up.
| Pt. No. | Age at Diagnosis (mo) | Interval to Diagnosis (days) | CAA Z Score | ||
|---|---|---|---|---|---|
| Baseline | 1 Yr | 3–5 Yr | |||
| No-abciximab group | |||||
| 1 | 3 | 7 | 27.28 | 12.8 | — |
| 2 | 5 | 9 | 26.55 | 3.5 | — |
| 3 | 7 | 20 | 16.52 | 7.23 | 2.75 |
| 4 | 8 | 14 | 11.71 | 4.6 | 0.69 |
| 5 | 10 | 35 | 39.99 | 35.6 | 27.96 |
| 6 | 43 | 10 | 33.6 | 38.05 | 29.7 |
| 7 | 79 | 10 | 24.84 | 24.02 | 24.76 |
| Median | Mean | ||||
| 8 | 10 | 25.8 ± 9.5 | 18 ± 14.6 | 17.1 ± 14.2 ⁎ | |
| Δ Z-score from baseline | −7.8 ± 9.0 | −8.2 ± 5.9 | |||
| Abciximab group | |||||
| 1 | 2 | 10 | 10.32 | — | −1.2 |
| 2 | 4 | 9 | 26.8 | 26.15 | 7.56 |
| 3 | 5 | 14 | 16.3 | 7.59 | 0.51 |
| 4 | 5 | 14 | 19.11 | 4.6 | 1.2 |
| 5 | 5 | 11 | 17.11 | 2.4 | — |
| 6 | 7 | 14 | 22.71 | — | 3.31 |
| 7 | 18 | 13 | 28.88 | 29.21 | 18.79 |
| 8 | 23 | 14 | 17.84 | 8.26 | 3.62 |
| 9 | 23 | 9 | 10.28 | 4.6 | 2.07 |
| 10 | 34 | 13 | 25.48 | 16.37 | 12.2 |
| 11 | 60 | 18 | 20.9 | 13.65 | 11.01 |
| Median | Mean | ||||
| 7 | 13 | 19.6 ± 6.2 | 12.5 ± 9.7 † | 5.9 ± 6.3 ⁎ | |
| Δ Z-score from baseline | −7.7 ± 5.3 | −14.0 ± 4.0 ‡ | |||
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