Optimization of oral anticoagulation in patients with atrial fibrillation: The challenge remains open

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its prevalence has been rising globally.1 This increase is driven by several factors, including an aging population, the escalating prevalence of cardiovascular risk factors such as hypertension, diabetes and obesity,2 and improved detection made possible by advancements in monitoring technologies, including wearable devices and other digital tools.3, 4 Recent estimates indicate a dramatic rise in the global AF epidemiological burden, with a prevalence of 46.3 million individuals worldwide in 20161 and an estimated incidence of 4.7 million in 2019.5 Data from a recent study further highlight this trend, showing 4.48 million new cases of AF in 2021 [95% uncertainty interval (UI): 3.61–5.70], marking a 137% increase in absolute cases since 1990. Mortality attributed to AF during the same year reached 0.34 million (95% UI: 0.29–0.37), with women experiencing higher deaths than men.6 Interestingly, while AF prevalence continues to rise, AF-related ischemic stroke risk is declining over time. That trend appears to align with the increasing use of oral anticoagulants (OACs) for stroke prevention.7 However, the persistent underutilization and inappropriate dosing of OACs remain a critical challenge and a missed opportunity for optimizing outcomes.8 In the present issue of the journal, Kefale et al.9 reported on a retrospective single-centre study evaluating the appropriateness of OAC use in AF patients at hospital admission and discharge, assessing whether hospitalization improves care. Of 2895 AF patients, hospitalized for any reason, identified between January 2021 and December 2022, 902 were included in the analysis (mean age 76.8 years; 59.8% male). Of note, patients with AF diagnosed within 3 months prior to their index admission, secondary AF and a single episode of AF that resolved by cardioversion without recurrence were excluded. OAC treatment appropriateness was assessed using the CHA2DS2-VA score (according with Australian guidelines). At admission, only 52.9% of patients received appropriate stroke prevention therapy, with 27.6% not on OAC despite being eligible. Common errors included lack of OAC in eligible patients (58.6%) and direct oral anticoagulant (DOAC) underdosing (15.5%). Multivariable analysis showed that a high ORBIT bleeding risk score was associated with inappropriate therapy. At discharge, OAC use improved to 73.8% of eligible patients, reflecting a 37.2% increase in therapy appropriateness. Of patients receiving inappropriate therapy at admission, 49% were discharged on guideline-concordant therapy. Despite these improvements, 26.2% still received inappropriate OAC therapy at discharge, primarily due to lack of OAC prescription (58.6%) or underdosing (15.5%). Factors associated with better discharge practices included admission to cardiology or stroke wards (adjusted odds ratio (aOR): 1.9; 95% CI: 1.1–3.3 and aOR: 13.8, 95% CI: 1.5–127.6, respectively), AF as the primary admission reason (aOR: 2.1; 95% CI: 1.1–3) and heart failure as a comorbidity (aOR: 1.6; 95% CI: 1.1–2.4). Conversely, advancing age (aOR: 0.97 per year, 95% CI: 0.96–0.99) decreased the likelihood of receiving appropriate therapy. These findings underscore that, despite encouraging improvements in guideline-concordant therapy uptake, stronger implementation efforts remain essential. Additionally, the data point to key areas for targeted improvement, including multidisciplinary patient care, accurate patient evaluation, risk factor modification, appropriate application of bleeding risk scores and correct DOAC dosing. Integrated multidisciplinary care, which includes proper anticoagulation when indicated, rate- or rhythm control and management of comorbidities, has shown significant benefits, even in complex clinical scenarios and patient populations.10 A holistic yet streamlined approach to patient care has been advocated by current European and American guidelines and has been summarized with different acronyms such as ABC, SOS and AF-CARE. All three of these frameworks focus on assessing thromboembolic risk using validated tools like CHA2DS2-VASc or CHA2DS2-VA scores to inform appropriate anticoagulation, managing symptoms through rate- or rhythm control and addressing comorbidities.11 In this context, the findings by Kefale et al.9 underscore that patients admitted to cardiology or stroke wards were more likely to receive guideline-concordant OAC therapy. This highlights the critical role of multidisciplinary teams that integrate diverse healthcare professionals and specialties to improve adherence to evidence-based care, possibly leading to better outcomes. The evaluation of the risk–benefit balance of OAC is a crucial component of patient assessment. In the study by Kefale et al.,9 a high bleeding risk, as determined by the ORBIT score, was associated with OAC underprescription. These findings indicate that bleeding risk scores are still frequently used to assess potential contraindications to OAC. However, bleeding risk reflects a combination of modifiable and non-modifiable factors, and bleeding risk scores primarily aim to highlight modifiable risks for mitigation and to identify high-risk patients for closer monitoring. While these tools only modestly predict major bleeding events, their true value lies in guiding clinicians to intervene on correctable risk factors rather than determining OAC eligibility.12 DOAC underdosing remains a significant clinical challenge, with up to 20% of patients receiving inappropriately low doses of DOACs.13 This issue is particularly common among older patients, those with a higher burden of comorbidities, or a history of hemorrhagic events, even if the same individuals often are at the highest risk of stroke. A meta-analysis of 16 studies involving 130,609 patients showed that off-label underdosing of DOACs increased the risk of ischemic stroke or systemic embolism compared with appropriate on-label dosing (hazard ratio [HR]: 1.22; 95% CI: 1.05–1.42), while the incidence of major bleeding remained comparable between groups (HR: 0.95; 95% CI: 0.82–1.11).14 Prescribing the correct DOAC dose, unless an absolute contraindication to anticoagulation is found, constitutes a crucial step in AF management, able to improve patient outcomes.1, 11 Patient hospitalization for any reason offers the chance for a comprehensive and dynamic patient reevaluation, taking into account changes in the clinical profile, renal function, potential drug interactions or other factors that may condition treatment with OACs. In the study by Kefale et al.,9 patients were admitted to a general medical ward in 39% of cases, a surgical ward in 20% of cases, and a cardiology ward in 19% of cases. This finding suggests that consultation among different physicians and specialists should be pursued in current medical practice, where integrated care and teamwork are needed for optimized decision-making11 (Figure 1). In this perspective, patient frailty also has to be assessed, since frailty, in its variable dimensions, is highly prevalent among patients with AF, ranging from 4.4% to 75.4%.15 Frailty is commonly linked to longer hospitalizations, more severe symptoms, a higher incidence of stroke and higher all-cause mortality,15 thus conditioning clinical decision-making. While the study by Kefale et al.9 did not evaluate frailty, managing OAC in this population poses unique challenges due to increased cognitive impairment, fall risk, polypharmacy and comorbidities. These factors can affect adherence to treatment, increase the likelihood of drug interactions and bleeding risk, all of which may influence clinical decisions. Despite these complexities, frailty alone should not preclude the use of OACs (preferably DOACs) in eligible AF patients. However, prescribing for frail patients requires a thorough evaluation of their baseline risk, personal values and preferences, alongside close clinical monitoring to optimize treatment outcomes.16 In conclusion, while notable progress has been made in optimizing anticoagulation therapy for patients with AF, significant gaps remain. Addressing these challenges requires a concerted effort to implement guideline-concordant care, particularly through multidisciplinary approaches that prioritize individualized treatment decisions. Enhancing the appropriate use of OACs, mitigating bleeding risks and managing frailty are critical steps toward improving outcomes. G Boriani reported small speaker fees from Bayer, Boehringer Ingelheim, Boston, Daiichi Sankyo, Microport, Janssen and Sanofi outside of the submitted work. He is P.I. of the ARISTOTELES project (European Horizon research Programme Grant N. 101,080,189). The other authors have no COIs to disclose.