This retrospective study reports a single-center experience of NOAC use in ACHD patients and found no thromboembolic and one major bleeding events during a median duration of 17 months of therapy.
Studies of NOAC use in ACHD patients are emerging but limited. A systemic review of NOAC use in ACHD patients included three studies with a total number of 766 patients . The annual rate of thromboembolic and major bleeding events was 0.98% (95% CI: 0.51–1.86) and 1.74% (95% CI: 0.86–3.49), respectively. One study included Fontan patients only, reporting a higher annual rate of both events, confirming the increased risk of thromboembolism in ACHD patients of complex severity . The two largest studies included 530 and 215 patients, not Fontan-exclusive [14, 15]. In these studies, the rate of complex severity of ACHD was about 40% and six and two thromboembolic events were registered, respectively. The total patient-years of follow-up was 896.3 years. Compared to our total patient-years of follow-up of 63.7 years, the low incidence of adverse events in our studies is plausible. However, compared to the largest included study of 530 patients, the median follow-up was 1 year, compared to 17 months in ours . Furthermore, the prevalence of complex ACHD severity, which is a major risk factor for thromboembolism, was only 27% . CHA2DS2-VASc > 2 was between 46 and 49% comparable to 40% in our study. For HAS-BLED, the scoring differed, with our study having 57% < 2 points and the other two studies reporting a higher 87–95% < 2 points [14, 15]. The risk of bleeding could thus be described to be higher in our study group, but the thromboembolic risk was lower with regard to the prevalence of complex severity defects and CHA2DS2-VASc scores. In one recent study, UNIVERSE Study evaluated the efficacy and safety of a rivaroxaban versus acetylsalicylic acid in 112 children during a high‐risk period early after Fontan procedure . The study period was 12 months. Nonmajor bleeding occurred in 6% of the Fontan patients on rivaroxaban versus 9% on acetylsalicylic acid. The thromboembolic overall event rate was 2% in the rivaroxaban group and 9% in the acetylsalicylic acid group. The study showed a low prevalence of both thrombotic and bleeding events in the rivaroxaban and the acetylsalicylic acid groups. The above-mentioned factors together with the lower patient-years of follow-up could be an explanation for the low rates of thromboembolism and bleeding.
The incidence of thromboembolism and major bleeding events in ACHD with good quality VKA therapy was reported in our Swedish study with 213 patients from the same center: 1.0 (95%CI: 0.6–1.6) and 1.4 (95%CI: 0.9–2.2), respectively. In this study, the median duration of therapy was 6.6 years (± 3.3 years) [4, 5]. The follow-up time was longer and could, in our study, be a reason for an underestimated incidence of events. Risk factors, such as female gender, lower age, heart failure and history of thromboembolism, for insufficient anticoagulation and complications (thromboembolism and major bleeding) in ACHD patients with VKA therapy could be reasons to consider NOAC as an alternative [4, 5]. As heart failure is one of the strongest predictors for stroke, an increased risk of renal failure in these patients may make VKAs a more plausible choice . NOAC was mostly discontinued according to plan, a new indication and change to another anticoagulant. Bleeding, other diseases and poor compliance were other less common causes for stopping NOAC therapy. As ACHD patients interact with health care at a younger age, compliance has been problematic. NOAC therapy can be an advantage in this patient group, especially for younger patients with normal heart and kidney function. NOAC can also be advantageous in patients on polypharmacy, which can interact with VKA. The benefits of NOAC, such as less regular blood tests, changing of dosing and consideration of food intake, could possibly appeal to younger patients and replace a potentially low compliance VKA therapy with its increased risk of thromboembolic events.
When comparing effectiveness and safety of NOAC to VKA for atrial fibrillation and venous thromboembolism, a systemic review and meta-analyses concluded NOAC to be comparable or superior to VKA in a non-ACHD population . The study suggested individualizing the choice of anticoagulation therapy based on the benefit and safety patient profiles and characteristics. Use of NOAC in ACHD patients is emerging with data showing effectiveness and safety, although with caution as studies are rather small and study populations are typically heterogenic. NOAC may thus seem like a practical anticoagulation alternative when patient profiles and characteristics are associated with insufficient anticoagulation and complications.