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

Abstract

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.

Thromboprophylaxis strategies for children with single-ventricle circulations (superior or total cavo-pulmonary connections) after stent implantation

“…[6][7][8][9][10][11][12] Reports have indicated that post-Fontan, there is a low risk of spontaneous thrombosis within the cavopulmonary connections. 17,18 Multiple previous studies, including single-centered, multi-centered, and meta-analyses, have shown that in patients with single-ventricle circulations, use of either aspirin or advanced anticoagulation (such as warfarin, heparin, or enoxaparin) is superior to no therapy for prevention of thrombus formation within the cavopulmonary connections in the absence of stent or other implanted devices. The most notable study, by McCrindle et al, was a randomisation to warfarin or aspirin therapy post-Fontan.…”

Frontiers in Fontan failure: Innovation and improving outcomes: A conference summary

“…17 Data comparing warfarin and aspirin in Fontan patients are limited with one multicenter, randomized clinical trial comparing warfarin and aspirin for primary thromboprophylaxis in children that showed similar outcomes. 19 As previously mentioned, safety and efficacy data are limited to case reports for the use of DOACs in Fontan patients. 18 Anticoagulation with warfarin can be performed safely, while achieving a high time within therapeutic range (TTR), using a pharmacist-managed anticoagulation clinic and this has been shown to reduce thromboembolic and bleeding complications, albeit in retrospective analysis and in adherent patients.…”

“…18 Anticoagulation with warfarin can be performed safely, while achieving a high time within therapeutic range (TTR), using a pharmacist-managed anticoagulation clinic and this has been shown to reduce thromboembolic and bleeding complications, albeit in retrospective analysis and in adherent patients. 19 As previously mentioned, safety and efficacy data are limited to case reports for the use of DOACs in Fontan patients. [20][21][22] It should be mentioned that the coagulation cascade is deranged in Fontan patients, which may help explain increased risk of both thromboembolic events and bleeding.…”

Non-vitamin K antagonist oral anticoagulants in adults with a Fontan circulation: are they safe

“…Patients with a Fontan circulation have a paradoxical coexistence of an increased risk of thromboembolism as well as bleeding 1–3. However, optimal thromboprophylaxis is unclear in this patient group due to limited evidence for efficacy and safety of anticoagulation or antiplatelet treatment, mostly consisting of retrospective studies performed in children or mixed cohorts with adult patients 4–7. Furthermore, conventional thromboprophylaxis such as vitamin K antagonists (VKAs) and aspirin have important limitations since they are suboptimal with considerable residual thromboembolic risk of 9.8%–13%,3 while there are difficulties achieving consistent international normalised ratio (INR) range with VKAs,4 and 52% of aspirin-treated Fontan adults having aspirin resistance 5.…”