A new strategy for monitoring of direct oral anticoagulants in patients with cyanotic and complex congenital heart disease.

Background: Patients with congenital heart disease (CHD) often require an oral anticoagulation. Vitamin K antagonists (VKA) are the standard treatment, however, an increased hematocrit in patients with secondary erythrocytosis due to cyanosis complicates the correct measurement of the international normalized ratio. Direct oral anticoagulants (DOAC) could be an alternative, but data on their efficacy and safety in complex and cyanotic CHD patients are scarce. This study proposes a new strategy of DOAC monitoring in these patients using D-dimers and DOAC trough levels. Methods: This is a retrospective study including cyanotic and complex CHD patients requiring oral anticoagulation. Clinical, cardiac imaging and laboratory data were collected before and after start of DOAC. The new monitoring strategy consists of determination of D-dimers and DOAC trough levels at 1-4 weeks, 1-6 months, 6-12 months, >1 year after start of DOAC. Results: Eleven patients were included. For 10 patients D-dimers and DOAC trough levels were in target range. In one patient, D-dimers increased continuously after start of DOAC despite dose escalation, suggesting insufficient DOAC efficacy and finally requiring a switch to VKA. D-dimers subsequently decreased under VKA to the therapeutic range. In three patients, one thromboembolic and two minor bleeding complications occurred. No major complications were observed. Conclusions: We propose a new strategy of monitoring of oral anticoagulation with DOAC and report its implementation in clinical routine. Highlighting the importance of pharmacokinetic and -dynamic monitoring, this strategy could improve safety and efficacy of DOAC in cyanotic and complex CHD which, however, requires a prospective validation.