Real‐world direct oral anticoagulant experience in atrial fibrillation: falls risk and low dose anticoagulation are predictive of both bleeding and stroke risk

Abstract

Background: Clinical trials have demonstrated that direct oral anticoagulants (DOAC) are non-inferior to vitamin K antagonist for stroke prevention in non-valvular atrial fibrillation (AF) with comparable safety outcomes; however, real-world Australian data are limited. Aims: To evaluate local real-world DOAC use focussing on safety, particularly in highrisk patients. Methods: A retrospective evaluation of 658 patients commenced or continued on DOAC between September 2013 and September 2016 for non-valvular AF at Northern Hospital, a tertiary hospital in Victoria, Australia was performed. Results: Factor Xa inhibitors were more commonly prescribed than direct thrombin inhibitors (83.3 vs 16.7%) for AF management. The median patient age was 75 years. The rate of clinically significant bleeding on anticoagulation was 3.13 per 100 personyears (including four deaths) with risk factors including history of bleeding (hazard ratio (HR) 3.52, 95% confidence interval (CI) 1.22-10.17), concurrent antiplatelet therapy (HR 2.62, 95% CI: 1.11-6.20) and high falls risk (HR 2.76, 95% CI: 1.26-6.08). Patients on low-dose DOAC had significantly higher bleeding risk compared with those on full dose (5.05 vs 1.82 per 100 person-years). The rate of thrombotic stroke despite anticoagulation was 1.34 per 100 person-years with risk factors including low dose anticoagulation (P = 0.034), high falls risk (P = 0.046) and previous stroke (P = 0.028). Conclusions: DOAC use in real-world Australian practice is safe and effective, consistent with international data. Low dose anticoagulation and falls risk are associated with increased bleeding and thrombotic risk demonstrating overlapping risk factors. Careful individualised patient risk assessment is still required as low dose anticoagulation is not without risks.

Link between cardiovascular disease and the risk of falling: A comprehensive review of the evidence

“…A recent study found that antiarrhythmic therapy usage increased the risk of fallrelated injury and syncope compared with rate lowering monotherapy, with the highest risk during the first 14 days [38]. Applicable AF patient populations may use anticoagulants to diminish stroke risk, and while serving a protective effect, may be considered as a potential modifier of the severity of injury following falls due to increased bleeding risk [35,[39][40][41][42].…”

“…Several studies have suggested that following trauma, direct oral anticoagulants are associated with less major bleeding events as compared with warfarin [40,[48][49][50] and better outcomes [51], although others have suggested no difference between them [52,53]. Many authors have concluded that while the benefits of anticoagulation most often outweigh the risks [54], a case-by-case basis should be undertaken to properly balance all possible outcomes [41,42,55]. The most recent ESC guidelines state that anticoagulation among patients with AF and fall history should only be withheld from patients with severe uncontrolled falls (e.g., epilepsy or multisystem atrophy), or in situations where compliance and adherence cannot be guaranteed [56].…”

Anticoagulant Therapy for Frail Patients with Atrial Fibrillation

“…Scores of ≥3 points are associated with a 3.74% annual risk of bleeding, which is considered a high risk ( 49 ). As a history of bleeding was found to be the greatest risk factor (HR 3.52, 95% CI 1.22-10.17) ( 50 ), caution is required for such cases.…”

“…No consensus has been reached regarding whether or not anticoagulants should be discontinued due to a history of one fall. However, if a fall has resulted in a hemorrhagic complication or has required hospitalization ( 17 , 50 ), withholding anticoagulant therapy is reasonable.…”

“…The concomitant use of antiplatelet drugs is another factor that can increase the risk of bleeding in patients on anticoagulant therapy ( 50 ). Some studies have shown that antiplatelet use is the greatest risk factor for not prescribing OAC to AF patients (OR 15.0, 95% CI 14.1-15.8) ( 61 ).…”