Impact of a modified anti-thrombotic guideline on stroke in children supported with a pediatric ventricular assist device

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Background

Stroke is the most feared complication associated with the Berlin Heart EXCOR pediatric ventricular assist device (VAD), the most commonly used VAD in children, and affects 1 in 3 children. We sought to determine whether a modified anti-thrombotic guideline, involving more intense platelet inhibition and less reliance on platelet function testing, is associated with a lower incidence of stroke.

Methods

All children supported with the EXCOR at Stanford from 2009 to 2014 were divided into 2 cohorts based on the primary anti-thrombotic guideline used to prevent pump thrombosis: (1) the Edmonton Anti-thrombotic Guideline (EG) cohort, which included children implanted before September 2012 when dual anti-platelet therapy was used with doses titrated to Thromboelastrography/PlateletMapping (TEG/PM); and (2) the Stanford Modified Anti-thrombotic Guideline (SG) cohort, which included children implanted on or after September 2012 when triple anti-platelet therapy was used routinely and where doses were uptitrated to high, weight-based dosing targets, with low-dose steroids administered as needed for inflammation.

Results

At baseline, the EG (N = 16) and SG (N = 11) cohorts were similar. The incidence rate of stroke in the SG cohort was 84% lower than in the EG cohort (0.8 vs 4.9 events per 1,000 days of support, p = 0.031), and 86% lower than in the previous Investigational Device Exemption trial (p = 0.006). The bleeding rate was also lower in the SG cohort (p = 0.015). Target doses of aspirin, clopidogrel and dipyridamole were higher (all p < 0.003), with less dosing variability in the SG cohort than in the EG cohort. There was no difference in adenosine diphosphate inhibition by TEG/PM, but arachidonic acid inhibition was higher in the SG cohort (median 75% vs 39%, p = 0.008).

Conclusions

Stroke was significantly less common in pediatric patients supported with the Berlin Heart EXCOR VAD using a triple anti-platelet regimen uptitrated to high, weight-based dosing targets as compared with the dual anti-platelet regimen titrated to PM, and without a higher risk of bleeding. Larger studies are needed to confirm these findings.

Section snippets

Study population

All children <18 years of age implanted with a Berlin Heart EXCOR pediatric VAD at Stanford University between January 2009 and June 2014 were included in our investigation. The study dates were chosen based on when there was consistent use of either the EG (before September 2012) or the Stanford Anti-thrombotic Guideline (SG) (September 2012 or after) in all EXCOR recipients (Table 1). Patients were excluded if they were implanted before 2009 (N = 8) to avoid introducing an era bias related to

Results

Between January 2009 and March 2014, 27 children underwent implantation of a Berlin Heart EXCOR pediatric VAD as a bridge to heart transplant at Stanford. Of these, 16 (59%) patients were implanted before September 2012 when the EG was used, whereas 11 (41%) were implanted after September 2012 when the SG was used as the anti-thrombotic guideline. The baseline characteristics of the study cohort are summarized in Table 2. There were no significant baseline differences between the EG and SG

Discussion

In this study, we found that use of a modified anti-thrombotic guideline, consisting of triplet anti-platelet therapy titrated to high, weight-based target doses—rather than values derived from TEG/PM—combined with prophylactic steroids as needed for inflammation was associated with a substantially lower incidence of stroke and device-related thromboembolism compared with usual care. We also found that the frequency of bleeding adverse events, defined according to standard pediatric INTERMACS

Disclosure statement

David N. Rosenthal has received research support from Berlin Heart, subsequently to the preparation of this manuscript, for the purpose of planning a larger trial of this protocol. This study was supported by a generous grant from the Kate Marra Family. The abstract was presented at the 38th annual meeting and scientific sessions of the International Society for Heart and Lung Transplantation, April 2015, Nice, France. The authors thank the inpatient and outpatient clinical teams for their

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1

The first 2 authors (D.N.R. and C.N.L.) contributed equally to this study.

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