Time in therapeutic range as a marker for thrombotic and bleeding outcomes in Fontan patients

Fontan patients managed with warfarin are at risk not only for thrombotic events, but also for bleeding episodes as a consequence of anticoagulation treatment. The aim of this study was to determine whether time spent in patient specified therapeutic range (TTR), when managed in a cardiology-based pharmacist managed anticoagulation clinic (PMAC), is a useful target metric for monitoring, as well as improving outcomes. A single center retrospective review was conducted evaluating TTR of all Fontan patients (n = 45) on warfarin managed in our outpatient cardiology pharmacist managed anticoagulation clinic (PMAC) during a 19 month time frame. The primary outcome was time spent within, above, and below therapeutic range. Secondary outcomes were thrombotic event (TE) incidence pre- and post PMAC enrollment and bleeding event incidence during PMAC management. Of the Fontan patients included, 55.6% were male and the median age at latest anticoagulation clinic follow-up was 19 years (IQR 13, 29). A composite 52.9 patient years of warfarin therapy was evaluated during the study time frame. The mean TTR for patients was 84.1 ± 5.2%. The most frequent reasons for non-therapeutic INRs were diet changes (42.8%), medication non-compliance (13.7%), and drug interactions (8.8%). Only one TE occurred during the study time frame. The incidence of TE in this population was decreased after PMAC enrollment (1 per 52.9 patient year versus 1 event per 17.4 patient year; p < 0.0002). Two major bleeds that required emergency department visit occurred during this time, none were cerebral or gastrointestinal. In Fontan patients anticoagulated with warfarin, a greater than 80% TTR can be achieved in a PMAC. Such high time in therapeutic range was associated with excellent outcomes, despite the obvious complexity of this population.