Impact of Cangrelor Use in Children Supported on Paracorporeal Ventricular Assist Devices

Abstract

<h3>Purpose</h3> Paracorporeal ventricular support devices (pVAD) are increasingly utilized in pediatric patients with end-stage heart failure as either bridge to recovery or as bridge to heart transplant. Unfortunately, thromboembolic events are not uncommon with use of pVAD with neurologic dysfunction occurring in 15-18% of patients. The optimal antithrombotic regimen is a subject of ongoing study. Cangrelor is an intravenous P2Y12 inhibitor used in adult patients undergoing percutaneous coronary intervention; its pharmacokinetic properties, including intravenous administration, short half-life, and avoidance of cytochrome p450 pathway, make it appealing as a safe and effective platelet inhibitor. We describe our pediatric experience with cangrelor anti-platelet therapy utilized throughout the duration of pVAD support. <h3>Methods</h3> Single-institution, retrospective chart review was conducted on all patients in a tertiary medical center with end-stage heart failure (INTERMACS level 1 or 2) supported with pVAD and receiving cangrelor infusion between June 2019 and October 2021. <h3>Results</h3> Seven patients were supported on continuous pVAD, and two were subsequently transitioned to pulsatile paracorporeal VAD. Median age was 8 months, and median weight was 6.7 kg. Four patients had a diagnosis of complex congenital heart disease. Three patients had dilated or restrictive cardiomyopathy, one of whom was admitted with fulminant myocarditis. Median number of days of continuous VAD support was 24.5 days (IQR 9-64 days). Cangrelor was initiated within 24 hours post-implant at a dose of 0.1 mcg/kg/min. Median time to therapeutic P2Y12 was 18 hours (IQR 13-32), and median duration of cangrelor therapy was 24 days. Mean dose to maintain therapeutic level was calculated, with a median of 0.25 mcg/kg/min (IQR 0.12-0.41 mcg/kg/min). Mean P2Y12 level was 169 PRU. Neurologic complications were encountered in one patient who died following hemorrhagic stroke. One patient experienced a GI bleed. <h3>Conclusion</h3> Cangrelor is safe and effective for use as a long-term antithrombotic medication in pediatric patients supported on pVAD. The frequency of adverse events was similar to that in previously published registry studies. The reliability of its intravenous administration and its short half-life make it appealing as an alternative to oral anti-platelet agents.