Apixaban plasma levels in patients with HeartMate 3 support

Background: Apixaban is increasingly used instead of vitamin K antagonists (VKAs) for long-term anticoagulation during HeartMate 3 (HM3) support. However, data on its pharmacokinetics in this context is lacking. We present real-world data on apixaban levels and outcomes in adult and pediatric HM3 patients, and evaluate our dosing strategy based on plasma sampling.

Methods: Since June-2023, all new HM3 recipients were initiated on apixaban. Additionally, hospitalized adult HM3 patients were transitioned from VKA to apixaban. Trough apixaban levels were measured in all patients, and dose adjustment was considered to exceed 50ng/ml.

Results: This retrospective study includes 34 HM3 patients, 4 pediatric (all primary use) and 30 adult patients (16 primary use). In primary use, apixaban was started at median of 14 (interquartile range [IQR]: 11-16, pediatric) and 11 (IQR: 6-13, adult) days postoperatively. No major coagulopathic events occurred during an overall follow-up of 3,191 patient-days. Six minor bleeding events occurred (0.69 events per patient-year), mostly (67%) during dual therapy with aspirin. Fourteen patients had dose adjustment; median trough and peak levels on final dosage were 73 (IQR: 50-92) and 179 (IQR: 133-242) ng/ml in the pediatric group and 109 (IQR: 83-144) and 176 (IQR: 134-228) ng/ml in the adult cohort, respectively. Inter- and intraindividual variation in apixaban peak levels was considerable, while trough levels showed less variability.

Conclusions: With a dosing strategy to target trough apixaban levels of >50ng/ml, there were no thrombotic events during a follow-up of 3,191 patient-days (of which 820 patient-days in children). We observed no major, and only few non-major bleeds, mainly in patients concomitantly taking aspirin.