Healthcare Professionals' perspectives on prescribing DOACs to frail older patients; The DOAC-FRAIL questionnaire

Healthcare Professionals' perspectives on prescribing DOACs to frail older patients; The DOAC-FRAIL questionnaire | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Healthcare Professionals' perspectives on prescribing DOACs to frail older patients; The DOAC-FRAIL questionnaire M. J Jong, A. D.H. Brys, D. Braeken, R. Pisters, D. J.A. Janssen, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7542541/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Jan, 2026 Read the published version in BMC Geriatrics → Version 1 posted 12 You are reading this latest preprint version Abstract Background DOACs are increasingly prescribed for atrial fibrillation and venous thromboembolism due to their ease of use and lack of monitoring requirements. Prescribing DOACs to frail older patients remains challenging due to higher bleeding and thrombo-embolic risks, comorbidities, polypharmacy, and underrepresentation in clinical trials. This study explored prescribing behavior of healthcare professionals (HCPs) in this complex clinical context. Methods An online questionnaire was distributed to HCPs involved in the care of frail older patients. The survey consisted of 27 items divided into three sections: demographics, factors influencing anticoagulant choice, and DOAC management. Descriptive statistics were used to evaluate outcomes. Results 355 HCPs completed the questionnaire. HCPs considered frailty(56.9%), fall risk(47.1%) and cognitive impairment (40.0%) when choosing an anticoagulant. Apixaban was the preferred DOAC(56.6%). 74.9% of HCPs did not measure DOAC levels in clinically stable patients, whereas 62.8% measured DOAC levels during acute hospitalizations. A large group of HCPs(46.4%) actively switched from VKA to DOAC, but expressed reservations due to fear for an increased bleeding risk. Almost half(48.1%) of HCPs indicated the need for clearer, tailored guidelines for DOAC use in frail older patients. Conclusions This study highlights the complexity of prescribing DOACs to frail older patients. While HCPs take multiple factors into account, a standardized approach to prescribing DOACs in this population remains lacking. In addition, almost half of HCPs expressed a need for guidelines regarding DOAC use in frail older patients. Hence, more research is needed to fill this knowledge gap and guide HCPs in clinical practice. Thrombosis Frail older patients DOAC Prescribing behavior Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 INTRODUCTION Direct oral anticoagulants (DOACs) are increasingly prescribed by healthcare professionals (HCPs) ( 1 , 2 ). DOACs are indicated for stroke prevention in atrial fibrillation (AF) and venous thromboembolism (VTE). Compared to vitamin K antagonists (VKAs), DOACs offer advantages such as ease of use, no need for laboratory monitoring and fewer interactions with food and drugs ( 3 , 4 ). In the general patient population, DOACs have a reasonable efficacy and safety profile related to bleeding risk. Consequently, DOACs are also increasingly prescribed to frail older population. However, specifically in this population prescribers must consider drug-drug interactions, comorbidities, fall risk, medication adherence and increased thromboembolic and bleeding risks. There is increasing evidence that DOACs should be prescribed with caution in frail older patients. First, the randomized controlled FRAIL-AF trial indicated a 69% increased risk of major bleeding and clinically relevant non-major bleeding when switching from a VKA to a DOAC in a frail older patient with AF ( 5 ). Second, our previous study has shown that DOAC levels measured during an acute hospital admission were outside the expected range in more than half of frail older patients ( 6 ). Furthermore, unusual high intra-individual variability in DOAC levels have been identified in the same population ( 7 – 9 ). These findings indicate the need to critically re-evaluate both the prescribing criteria for DOACs in the frail older population and the implementation strategies required to ensure their safe and effective use. Knowledge on how prescribers currently approach the prescription of DOACs to frail older patients is lacking. However, given the concerns outlined above, gaining insights into current prescribing practices is essential for the development of uniform guidelines for the use of DOACs in the frail older population. To explore this, we conducted a cross-sectional international study using an online questionnaire among HCPs . METHODS DESIGN AND POPULATION In this cross-sectional study, an online questionnaire was distributed among HCPs in the Netherlands and Belgium. This survey was developed by a team of five researchers with established expertise in the field of direct oral anticoagulants (DOACs) and the clinical management of frail older adults, in order to ensure both content validity and clinical relevance. The questionnaire was available in Dutch and French. An English version of the questionnaire is available as Supplementary Material. Since our focus was on DOAC use within the frail older population (age ≥70 years, Clinical Frailty Scale >5), the questionnaire was distributed to general practitioners, geriatricians, cardiologists, elderly care physicians(10) and physician assistants (last two are only applicable in the Netherlands), between April 2024 and January 2025. Distribution was primarily through a QR code or web link presented in newsletters of the medical associations involved, e.g. the Dutch Society of Internal Medicine (NIV), the Dutch Geriatrics Society (NVKG), the Dutch society of cardiology (NVVC), Healthcare in development (ZIO), the Belgian Society of Cardiology (BSC), the Dutch Association of Elderly Care Physicians Verenso), the Dutch society of Physician Assistants (NAPA), the Belgian Society of Gerontology and Geriatrics (BSGG), and General Physician society Domus Medica (LHV) with secondary distribution allowed through peer-to-peer sharing. ETHICS APROVAL AND CONSENT TO PARTICIPATE The medical ethics committee (METC) of the MUMC+ assessed the study and concluded that due to the nature of the study it does not fall under the scope of the Medical Research Involving Human Subjects Act (METC number 2021-2945). This study did not involve patient data or interventions Healthcare professionals (HCPs) were invited to participate on a voluntary basis. The survey was primarily distributed via a QR code or web link included in newsletters from the participating medical associations. Upon accessing the survey, HCPs were presented with a brief introduction outlining the purpose of the study, the voluntary nature of participation, the content of the survey, and the intended use of aggregated results for analysis and publication. Formal written informed consent was not required in accordance with applicable regulations, as completion of the survey was taken as implicit consent. DATA COLLECTION A web-based, secure software platform (Qualtrics XM) was used to build and distribute the questionnaire, followed by data collection and data-management. The statements and questions primarily focused on exploring prescribing behavior, managing and monitoring of DOAC therapy, and aimed to gain insight into the perceived knowledge in terms of available evidence and guideline recommendations for prescribing and managing DOAC use in frail older patients. The questionnaire was developed by the research team, based on existing literature, prior research experience, clinical experience and the findings from the previous conducted DOAC-FRAIL studies (6, 7). The questionnaire comprised 27 items across three sections. The first section included 5 questions on HCP demographics. The second section consisted of 16 statements and the third section contained 6 multiple-choice questions, both focusing on the prescription of anticoagulants, in particular DOACs, in frail older patients (S1). The themes evaluated were: (1) factors influencing the choice of anticoagulant (DOAC, VKA or low molecular weight heparin (LMWH)), (2) DOAC management approaches, (3) need for and use of DOAC level measurements, and (4) awareness of DOAC management guidelines and available evidence. HCPs were asked to rate the 16 statements on a 5-point Likert scale, with response options ranging from “always” to “never” and “strongly agree” to “strongly disagree”(11). At various points, respondents were given the opportunity to share reflections, comments or questions. STATISTICS Questionnaires were collected in Qualtrics XM and exported to IBM Statistical Package for Social Sciences (SPSS) version 28 for analysis. Descriptive statistics were applied to all quantitative results. The open-text comments were analyzed, categorized and textually summarized by one researcher. RESULTS RESPONDENTS DEMOGRAPHICS A total of 355 HCPs completed the questionnaire (Table 1 and S1). Most HCPs were based in a hospital (54.0%), followed by 24.2% working in general practice settings and 19.2% working in a nursing home (19.2%). The majority of HCPs was between 30 and 44 years of age (49.3%) (S2). Table 1. Demographics (n= 355) Medical specialty: Geriatrician Cardiologist Elderly care physician General practitioner Physician assistant Other** 93 (26.2%), in training 19 (5.4%) 58 (16.3%), in training 10 (2.8%) 59 (16.6%), in training 16 (4.5%) 80 (22.5%), in training 5 (1.4%) 10 (2.8%) 5 (1.4%) Healthcare facility: University hospital Peripheral hospital Nursing home General practice Other*** 58 (16.3%) 134 (37.7%) 68 (19.2%) 86 (24.2%) 6 (1.7%) Age group: 25-29 years 30-34 years 35-39 years 40-44 years 45-49 years 50-54 years 55-59 years 60-64 years 65-70 years Other**** 32 (9.0%) 70 (19.7%) 66 (18.6%) 39 (11.0%) 30 (8.5%) 40 (11.3%) 34 (9.6%) 24 (6.8%) 10 (2.8%) 10 (2.8%) Work experience: 0-5 years 6-10 years 11-15 years ≥ 16 years 83 (23.4%) 83 (23.4%) 59 (16.6%) 129 (36.3%) ** Gastroenterologist, cardiac surgeon and clinical pharmacologist *** Private clinic and rehabilitation center **** Age was not specified in additional remarks T HEME (1) FACTORS INFLUENCING THE CHOICE FOR ANTICOAGULATION TYPE In very old (>80 years) patients, patients with cognitive impairment and in frail patients, most HCPs prefer prescribing a DOAC instead of VKA or LWMH. When selecting an anticoagulant for the oldest patients (>80 years), key considerations included the absence of a need for laboratory based dose adjustments (need for monitoring) (n=263, 74,1%), adherence (n=168, 47.3%), efficacy (n=154, 43.4%) and side effects (n= 147, 41.1%), with these factors once again favoring the use of DOACs. When selecting an anticoagulant for patients with cognitive impairment, HCPs reported that their decisions were primarily influenced by the absence of a need for laboratory based dose adjustments (n=295, 73.0%), followed by medication adherence (n=188, 53.0%), efficacy (n=128, 36.1%) and side-effects (n=123, 34.6%). Comparable factors influenced anticoagulant selection in frail patients, with similar emphasis on the absence of a need for laboratory based dose adjustments (n=274, 77.2%), adherence (n=174, 49.0%), efficacy (n=153, 43.1%), and side-effects (n=140, 39.4%). Figure 1 illustrates the responses to the multiple-choice questions related to the choice of DOAC, VKA, or LMWH as anticoagulant options. Along with the previously mentioned factors, healthcare professionals were asked whether, based on their experience, a specific anticoagulant (DOAC, VKA, or LMWH) affected the occurrence of bleeding complications in frail older patients (missing data 7.9%): HCPs predominantly observed fewer bleeding complications with DOACs (81.4%) than with VKA (10.7%) or LMWH (0.0%). The majority of HCPs considered frailty (often 39.2%, always 17.7%), cognitive function (often 26.8%, always 13.2%), and the risk of falls (often 31.3%, always 15.8%) when making this decision. However, age was a factor that most HCPs did not prioritize when choosing between DOACs and VKAs, with 29.3% rarely considering it and 27.9% never considering it. An significant percentage of respondents actively switched from VKA to DOAC in frail older patients (often 37.7%, always 8.7% versus never 7.6%, rarely 22.8%). Figure 2 presents four statements outlining factors influencing the decision between DOACs and VKA. Comments of HCPs A small number of respondents (n=16) commented that a switch from a VKA to a DOAC was typically made when the INR was unstable or when issues arose with obtaining INR measurements. Additionally, few respondents (n=13) reported switching from a VKA to a DOAC less often following the FRAIL-AF study (5). THEME (2) DOAC MANAGEMENT APPROACHES The majority of HCPs preferred apixaban (56.6%) as DOAC in frail older patients (rivaroxaban 9.6%, edoxaban 16.9%, dabigatran 1.4% and no preference 14.9%). Most of the respondents did not choose a dose reduction because of frailty (never 30.4%, rarely 37.2%), regardless of renal function and/or weight (Figure 3). More than half of HCPs reported conducting annual evaluation of adherence/compliance, complications, and renal function when prescribing DOACs (annual weighing consultation), with 30.4% doing so frequently and 37.2% always. In contrast, 2.8% indicated they never, 13.5% rarely conducted this annual evaluation, and 15.8% remained neutral on the matter. Additionally, the majority of HCPs checked at each patient contact if the DOAC dose was still in line with recommendations for renal function and made adjustments when necessary. The vast majority of HCPs considered DOACs as beneficial for the frail older population, due to fixed-dose prescription and no need for laboratory based dose adjustments (agree 46.8%, strongly agree 36.3%). THEME (3) NEED FOR AND USE OF DOAC LEVEL MEASUREMENTS HCPs did not determine a DOAC level often (rarely 18.3%) and most HCPs do not measure a DOAC level at all (never 74.9% versus often 0.0% and always 1.7%). In addition, HCPs did not often adjust dosage based on the DOAC level (never 67.6%, rarely 11.8% versus 0.6%, always 1.7%) (Figure 4). During acute hospitalization HCPs very rarely measured a DOAC level (never 52.4%, rarely 10.4% versus often 0.6, always 0.30%). 56.9% of HCPs were assured that when using a DOAC in frail older patients, DOAC levels would be within the expected range (on-therapy) despite the absence of monitoring (often 38.9%, always 18%). When asked specifically about the reason for DOAC level measurement (when measured), 25.4% (n=90) indicated that this was performed because of bleeding and 24.8% (n=88) because of thrombosis under DOAC use. Other reasons included acute renal impairment, evaluation of efficacy, a history of a gastric bypass or the need for surgery. THEME (4) DOAC MANAGEMENT GUIDELINES AND AVAILABLE EVIDENCE 20.0% of HCPs stated that there was insufficient evidence for safe prescription of DOACs in the frail older population (agree 17.7%, strongly agree 2.3%). Furthermore, 77.7% of HCPs indicated that there should be clearer recommendations regarding DOAC management in this specific population (strongly agree 19.7%, agree 58.0%; Figure 5). DISCUSSION This study provides new insights into oral anticoagulant prescribing behavior of HCPs to frail older patients. First, HCPs (in general) preferred DOACs over VKAs. Second, the study found that cognitive impairment, fall risk and frailty were all key factors considered when determining for the appropriate type of anticoagulation treatment, while age was not. In addition, the primary reasons HCPs preferred DOACs over VKA were no need for monitoring and medication adherence. Notably, 46.4% of HCPs actively converted patients from VKA to DOAC, although additional comments suggested that several HCPs have abandoned this practice since the publication of the FRAIL-AF study (5). Fourth, an important observation was that only 67.6% of HCPs performed an annual treatment assessment in frail older patients using DOACs. In addition, the vast majority of HCPs did not measure DOAC levels in this specific population, while only 56.9% of HCPs expressed confidence that DOAC levels would be within the expected range. Lastly, a significant portion of HCPs expressed the need for explicit recommendations regarding DOAC therapy in frail older patients. HCPs favored DOACs for frail, cognitively impaired patients or patients at risk of falls. The preference for DOACs aligns with evidence suggesting they offer advantages over VKAs such as reduced need for laboratory drug level monitoring and fewer food interactions (12). However, literature shows growing awareness of issues such as poor medication adherence (13), the impact of polypharmacy (4, 14), comorbidities (15) and renal failure in relation to DOAC use (16). Moreover, the underrepresentation of frail older adults in major clinical trials complicates anticoagulant selection and limits the applicability of trial results to real-world practice. Interestingly, despite the preference for DOACs, our survey revealed reservations about switching from VKAs to DOACs. This finding echoes concerns raised by the recent randomized FRAIL-AF study, which indicated an increased risk of major and clinically relevant non-major bleeding complications in frail older patients when switching from VKAs to DOACs (5). In line with the aforementioned, the recently updated guidelines for the management of atrial fibrillation by the European Society of Cardiology, developed in collaboration with the European Association for Cardio-Thoracic Surgery, recommend that frail patients aged 75 years or older who are on polypharmacy and stable on a VKA continue VKA therapy rather than switch to a DOAC (17). Thus, while DOACs are considered an appropriate choice for the frail older population, HCPs should be increasingly cautious about making active switches, particularly in light of bleeding risks. Further research is warranted to determine whether the ‘one-size-fits-all’ approach of DOAC prescribing is truly appropriate and safe for this population. HCPs’ preference for apixaban as the most suitable DOAC for frail older patients is consistent with existing literature, which highlights the drug's favorable pharmacokinetic profile and lower bleeding risk compared to other DOACs such as rivaroxaban or edoxaban (18). In addition, many HCPs adjust dosages based on age and/or frailty , and not solely based on renal function or weight (19). Recent findings display benefits of reduced doses in older adults with multimorbidity (20). Annual weighing consultation was acknowledged by only 67.6% of the respondents, which is concerning. The issue of monitoring is a critical aspect of anticoagulation management. The 2018 European Heart Rhythm Association (EHRA) guidelines concluded that DOAC treatment requires vigilance due to potentially severe complications, particularly as the target patient population tends to be of older age and frail (19). In patients aged ≥75 and/or with increased frailty, blood tests evaluating hemoglobin, liver function and renal function are recommended at least every 6 months (19). The 2021 practical guide on the use of non-vitamin K antagonist oral anticoagulants (EHRA) strongly advises a regular weighing consultation for patients with renal failure, older age, comorbidities, frailty or cognitive decline. Follow-up should include evaluation of adherence, thromboembolic events, bleeding events, side effects, co-medication, need for blood sampling, modifiable risk factors and optimal DOAC and correct dosing (21). To facilitate this, recent studies suggest reassessing the role of anticoagulation clinics to monitor patients on DOACs, similar to the approach used for those on VKAs (22-24). The low number of HCPs performing these weighing consultations is possibly due to a paucity in implementing these guidelines. HCPs did not or very rarely measure DOAC levels. Even in acute situations or during hospitalization, DOAC levels were not or rarely measured by HCPs. Interestingly, only 56.9% were convinced that DOAC levels would be within the on-therapy range when used in frail older patients. Not measuring DOAC levels may, for a large part, reflect lack of availability and/or knowledge about indications for DOAC level testing or is a consequence of an cost-effectiveness assessment. It may also be linked to the notion that DOACs, unlike VKAs, generally do not require regular dose adjustment for optimizing therapeutic efficacy. Furthermore, there is a lack of information regarding the clinical consequences of deviant levels under medically stable conditions. However, elevated levels have been associated with an increased risk of bleeding, while lower levels are linked to a higher risk of thrombosis(25-28). The International Council for Standardization in Haematology recommends the option of DOAC level testing in patients with advanced age, severe renal failure, high body mass index, drug interactions or prior to an intervention with high bleeding risk (29). In contrast, the EHRA guidelines recommend measuring DOAC levels in emergency situations such as bleeding, stroke or overdose, as well as in medication interactions, extremes in body weight and renal impairment (21). ESC guidelines recommend measurements in the presence of stroke or bleeding conditions and the need for acute surgery only (17). In addition, in cases of acute life-threatening bleeding, when reversal agents are being considered, measuring DOAC levels is advised to assess the contribution of the DOAC and to support decision-making for interventions (30). The infrequent measurement of DOAC levels by HCPs during acute hospitalizations warrants further investigation, as recent studies suggest that DOAC level measurements could be beneficial in improving the management of patients with acute conditions or complications (29, 31). Importantly, this study revealed that of HCPs (20.0%) stated that there was insufficient evidence to support the prescription of DOACs in the frail older population. In addition, a substantial number of HCPs expressed the need for clearer recommendations and guidelines specifically tailored to frail older patients. The desire for more evidence and specific recommendations reflects the broader clinical uncertainty regarding the optimal approach to DOAC use in frail, older patients, as well as the challenges HCPs face in balancing the associated benefits and risks. This underscores a critical gap in clinical knowledge and emphasizes the need for further research, particularly randomized controlled trials, focusing on the safety and efficacy of DOACs in this population, serving as a first step toward developing tailored recommendations in clinical guidelines. The current study has noteworthy strengths. First, the questionnaire was specifically focused on DOAC treatment in frail older patients, addressing a diverse group of HCPs, including those working in university and non-university hospitals, nursing homes, and general practice clinics. Second, this is the first study to provide insight into the use of DOAC level measurements in daily practice by HCPs, as well as to address the need for tailored guidelines for the frail older population. A limitation of the study is the inability to calculate the response rate due to several factors: (1) no data was available on the exact number of members receiving the newsletter from the relevant professional associations, (2) HCPs may have received the survey through multiple associations, and (3) it was allowed to distribute the survey via peer-to-peer channels. However, a total of 355 HCPs completed the survey, representing a relatively large group of participants. Another limitation of the study is that the design and method of survey distribution may limit the generalizability of the findings to other healthcare systems in Europe and beyond. CONCLUSION In conclusion, this study provides valuable insights into the complex decision-making process surrounding the use of DOACs in frail older patients. In short, HCPs do not follow a uniform approach when prescribing and managing DOACs in frail older patients. In addition, a significant proportion of HCPs are seeking for tailored recommendations in international guidelines. Thus, there is a need for further research on DOAC management in this specific population with the goal of ensuring safer use of DOACs and providing clinically applicable recommendations in guidelines. Declarations ACKNOWLEDGMENTS Author contributions: F. Magdelijns and M. de Jong conceived the study. F. Magdelijns, M. de Jong, S. Robben, D. Janssen and A. Brys contributed to the design of the study and drafting the questionnaire. All authors helped distribute the questionnaire to DOAC prescribing healthcare professionals. F. Magdelijns and M. de Jong collected all data. F. Magdelijns, A. Brys, H. ten Cate, K. Winckers and M. de Jong contributed to the interpretation of the data. M. de Jong wrote the manuscript. F. Magdelijns, A. Brys. K. Winckers and H. ten Cate revised the manuscript. All authors reviewed and approved the final version of the manuscript. Disclosures: HtC received research support from Astra Zeneca and consulting fees from Astra Zeneca, Galapagos, Alveron and Novostia. He is shareholder of CoagulationProfile, a spinoff diagnostic company from Maastricht University. All revenues are deposited at the CARIM institute for research purposes. He is a former chairman of board of the Dutch Federation of Anticoagulation clinics, which is a pro deo position. RDC received consultancy/speakers fees from Sanofi, Milestone, Daiichi-Sankyo, Janssen, Pfizer, Bristol-Myers Squibb, Menarini, and Amarin, travel support from Amarin and Daiichi-Sankyo, and participated in the Data Safety Monitoring Board of NOAH-AFNET6 (Daiichi- Sankyo), all outside this project. In addition, he is member of the Editorial Board of European Heart Journal. DJAJ received lecture fees from Chiesi, AstraZeneca and Abbott within the past three years, all paid to the institution and outside the submitted work. Sponsor’s Role: There was no funding or sponsor's role in the design, methods, subject recruitment, data collection, analysis, or preparation of the paper. Data Availability The dataset used and analysed during the current study are available from the corresponding author on reasonable request. References Wheelock KM, Ross JS, Murugiah K, Lin Z, Krumholz HM, Khera R. Clinician Trends in Prescribing Direct Oral Anticoagulants for US Medicare Beneficiaries. JAMA Netw Open. 2021;4(12):e2137288. de Vries TAC, Bavalia R, Chu G, Xiong H, van de Wiel KM, van Ballegooijen H, et al. Prescription and switching patterns of direct oral anticoagulants in patients with atrial fibrillation. Research and Practice in Thrombosis and Haemostasis. 2024;8(6):102544. Zeng S, Zheng Y, Jiang J, Ma J, Zhu W, Cai X. Effectiveness and Safety of DOACs vs. Warfarin in Patients With Atrial Fibrillation and Frailty: A Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2022;9:907197. Ferri N, Colombo E, Tenconi M, Baldessin L, Corsini A. Drug-Drug Interactions of Direct Oral Anticoagulants (DOACs): From Pharmacological to Clinical Practice. Pharmaceutics. 2022;14(6). Joosten LPT, van Doorn S, van de Ven PM, Köhlen BTG, Nierman MC, Koek HL, et al. Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial. Circulation. 2024;149(4):279-89. de Jong MJ, Saadan H, Hellenbrand DLS, Ten Cate H, Spaetgens B, Brüggemann RAG, et al. The DOAC-FRAIL study, evaluation of direct oral anticoagulant-levels in acutely admitted frail older patients: An exploratory study. J Am Geriatr Soc. 2024;72(7):2249-53. de Jong MJ, Saadan H, van der Hooft BHM, Hellenbrand DLS, Brüggemann RAG, Ten Cate H, et al. Intra-Individual Variability of Direct Oral Anticoagulant Levels in Frail Older Patients upon, during, and after Acute Hospitalization: the DOAC-FRAIL Study. J Am Med Dir Assoc. 2024;25(12):105280. Toorop MMA, van Rein N, Nierman MC, Vermaas HW, Huisman MV, van der Meer FJM, et al. Inter- and intra-individual concentrations of direct oral anticoagulants: The KIDOAC study. J Thromb Haemost. 2022;20(1):92-103. Testa S, Tripodi A, Legnani C, Pengo V, Abbate R, Dellanoce C, et al. Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics. Thrombosis Research. 2016;137:178-83. Koopmans RT, Lavrijsen JC, Hoek JF, Went PB, Schols JM. Dutch elderly care physician: a new generation of nursing home physician specialists. J Am Geriatr Soc. 2010;58(9):1807-9. Likert R. A technique for the measurement of attitudes. Archives of Psychology. 1932. Chen A, Stecker E, B AW. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. J Am Heart Assoc. 2020;9(13):e017559. Salmasi S, Safari A, Kapanen A, Adelakun A, Kwan L, MacGillivray J, et al. Oral anticoagulant adherence and switching in patients with atrial fibrillation: A prospective observational study. Res Social Adm Pharm. 2022;18(11):3920-8. Harskamp RE, Teichert M, Lucassen WAM, van Weert H, Lopes RD. Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation. Cardiovasc Drugs Ther. 2019;33(5):615-23. Kajy M, Mathew A, Ramappa P. Treatment Failures of Direct Oral Anticoagulants. Am J Ther. 2021;28(1):e87-e95. Hahn K, Lamparter M. Prescription of DOACs in Patients with Atrial Fibrillation at Different Stages of Renal Insufficiency. Adv Ther. 2023;40(10):4264-81. Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns H, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314-414. Kim DH, Pawar A, Gagne JJ, Bessette LG, Lee H, Glynn RJ, et al. Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation : A Cohort Study. Ann Intern Med. 2021;174(9):1214-23. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330-93. Hayes KN, Zhang T, Kim DH, Daiello LA, Lee Y, Kiel DP, et al. Benefits and Harms of Standard Versus Reduced‐Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation. Journal of the American Heart Association. 2023;12(21):e029865. Steffel J, Collins R, Antz M, Cornu P, Desteghe L, Haeusler KG, et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021;23(10):1612-76. Tripodi A, Chantarangkul V, Poli D, Testa S, Bucciarelli P, Peyvandi F. The role of anticoagulation clinics needs to be reassessed to include follow up of patients on direct oral anticoagulants. Thromb Res. 2023;225:11-5. Sylvester KW, Chen A, Lewin A, Fanikos J, Goldhaber SZ, Connors JM. Optimization of DOAC management services in a centralized anticoagulation clinic. Res Pract Thromb Haemost. 2022;6(3):e12696. Albert V, Baumgartner PC, Hersberger KE, Arnet I. How do elderly outpatients manage polypharmacy including DOAC - A qualitative analysis highlighting a need for counselling. Res Social Adm Pharm. 2022;18(6):3019-26. Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014;63(4):321-8. Ruff CT, Giugliano RP, Braunwald E, Morrow DA, Murphy SA, Kuder JF, et al. Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet. 2015;385(9984):2288-95. Testa S, Paoletti O, Legnani C, Dellanoce C, Antonucci E, Cosmi B, et al. Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost. 2018;16(5):842-8. Testa S, Legnani C, Antonucci E, Paoletti O, Dellanoce C, Cosmi B, et al. Drug levels and bleeding complications in atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost. 2019;17(7):1064-72. Douxfils J, Adcock DM, Bates SM, Favaloro EJ, Gouin-Thibault I, Guillermo C, et al. 2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants. Thromb Haemost. 2021;121(8):1008-20. Specialisten FvM. Antitrombotisch beleid. 2021-2025. Ahuja T, Raco V, Bhardwaj S, Green D. To Measure or Not to Measure: Direct Oral Anticoagulant Laboratory Assay Monitoring in Clinical Practice. Adv Hematol. 2023;2023:9511499. Additional Declarations No competing interests reported. Supplementary Files SUPPLEMENTARYMATERIAL.docx Cite Share Download PDF Status: Published Journal Publication published 23 Jan, 2026 Read the published version in BMC Geriatrics → Version 1 posted Editorial decision: Revision requested 12 Nov, 2025 Reviews received at journal 03 Nov, 2025 Reviews received at journal 27 Oct, 2025 Reviews received at journal 25 Oct, 2025 Reviewers agreed at journal 22 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers invited by journal 29 Sep, 2025 Editor assigned by journal 23 Sep, 2025 Editor invited by journal 23 Sep, 2025 Submission checks completed at journal 22 Sep, 2025 First submitted to journal 22 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7542541","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":527320678,"identity":"d247f628-0ef0-41e3-9caf-8aadb0ff6d96","order_by":0,"name":"M. J Jong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYFAC5gYGBgMgfQBCyUGFLfBoYUTVYgwVliCghQGiBQQSGwhp0W1vbPxcUGDDwHe8gaHg447a9LUzshM/MO7ArcXszMFm6RkGaQySZw4wGM48czx3243czRKMZ/BouZHYIM1jcJjB4EYCgzFv2zGQlm0MjG14tNx/2Pybx+A/g8H9B2At6WYEtdxgbAPacgBoCwNIS00CYS1nEtuseQySeSTPJDYYzmw7YLjtzNvNEon4tBw/fPg2zx87Ob7jh48ZfGyrkzc7nrvxw8c2G5xaYIAHGEFtwKg8DOEmENQAAcwPGBjqiFQ7CkbBKBgFIwkAAHVZV2sZ0cWRAAAAAElFTkSuQmCC","orcid":"","institution":"Thrombosis Expert Center Maastricht, Maastricht University Medical Center+","correspondingAuthor":true,"prefix":"","firstName":"M.","middleName":"J","lastName":"Jong","suffix":""},{"id":527320681,"identity":"861cf655-d341-43be-a7aa-f0b18da4197f","order_by":1,"name":"A. D.H. Brys","email":"","orcid":"","institution":"Ghent University Hospital","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"D.H.","lastName":"Brys","suffix":""},{"id":527320684,"identity":"c46835a4-d28a-44ab-9c58-c74a3819abb9","order_by":2,"name":"D. Braeken","email":"","orcid":"","institution":"Thrombosis Expert Center Maastricht, Maastricht University Medical Center+","correspondingAuthor":false,"prefix":"","firstName":"D.","middleName":"","lastName":"Braeken","suffix":""},{"id":527320686,"identity":"9cd9fb35-c83c-4c89-8f79-09c29ea8168e","order_by":3,"name":"R. Pisters","email":"","orcid":"","institution":"Rijnstate Hospital","correspondingAuthor":false,"prefix":"","firstName":"R.","middleName":"","lastName":"Pisters","suffix":""},{"id":527320689,"identity":"93edee2b-085e-4281-8a97-351295258642","order_by":4,"name":"D. J.A. Janssen","email":"","orcid":"","institution":"Maastricht University","correspondingAuthor":false,"prefix":"","firstName":"D.","middleName":"J.A.","lastName":"Janssen","suffix":""},{"id":527320690,"identity":"ce2dec6f-280e-4258-b6e2-eacf532fbeee","order_by":5,"name":"S. Altintas","email":"","orcid":"","institution":"AZ Vesialus","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"","lastName":"Altintas","suffix":""},{"id":527320692,"identity":"3b559ca0-4b89-4411-9015-a743a496e755","order_by":6,"name":"S. H.M. Robben","email":"","orcid":"","institution":"Elisabeth-TweeSteden Ziekenhuis","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"H.M.","lastName":"Robben","suffix":""},{"id":527320695,"identity":"27c06909-d1bb-453c-a4bc-4502f033bc2f","order_by":7,"name":"S. Nicolaï","email":"","orcid":"","institution":"General Practitioner","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"","lastName":"Nicolaï","suffix":""},{"id":527320697,"identity":"c6e4bb38-653d-487f-a33a-204aaf22a46a","order_by":8,"name":"C. Eurlings","email":"","orcid":"","institution":"Laurentius Ziekenhuis","correspondingAuthor":false,"prefix":"","firstName":"C.","middleName":"","lastName":"Eurlings","suffix":""},{"id":527320698,"identity":"f5855dab-7e16-4a16-9fb2-0844d22c97ca","order_by":9,"name":"A. Zwietering","email":"","orcid":"","institution":"Laurentius Ziekenhuis","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"","lastName":"Zwietering","suffix":""},{"id":527320699,"identity":"eb9528fd-e4b2-44f0-ba6e-2b4da9704ba0","order_by":10,"name":"M. Jonghe","email":"","orcid":"","institution":"Université Catholique de Louvain","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"","lastName":"Jonghe","suffix":""},{"id":527320700,"identity":"4ce7c899-4e8a-4d0e-91b8-0ae6af3110c4","order_by":11,"name":"B. Vaes","email":"","orcid":"","institution":"KU Leuven","correspondingAuthor":false,"prefix":"","firstName":"B.","middleName":"","lastName":"Vaes","suffix":""},{"id":527320701,"identity":"41125b03-ec64-4fc8-beed-91fc17509081","order_by":12,"name":"T. Backer","email":"","orcid":"","institution":"Ghent University Hospital","correspondingAuthor":false,"prefix":"","firstName":"T.","middleName":"","lastName":"Backer","suffix":""},{"id":527320702,"identity":"88cc9fae-a3fc-4d46-b3c0-97ee7475d858","order_by":13,"name":"M. Grymonprez","email":"","orcid":"","institution":"Ghent University Hospital","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"","lastName":"Grymonprez","suffix":""},{"id":527320705,"identity":"017bb9fd-a82b-426f-a1b0-8134658edb83","order_by":14,"name":"H. Joosten","email":"","orcid":"","institution":"Maastricht University Medical Centre","correspondingAuthor":false,"prefix":"","firstName":"H.","middleName":"","lastName":"Joosten","suffix":""},{"id":527320707,"identity":"0085efd0-f7f5-4bcc-bc84-224c1020d065","order_by":15,"name":"H. ten Cate","email":"","orcid":"","institution":"Thrombosis Expert Center Maastricht, Maastricht University Medical Center+","correspondingAuthor":false,"prefix":"","firstName":"H.","middleName":"ten","lastName":"Cate","suffix":""},{"id":527320709,"identity":"e9ae4965-9f2e-437b-aa74-429c8e212679","order_by":16,"name":"K. Winckers","email":"","orcid":"","institution":"Thrombosis Expert Center Maastricht, Maastricht University Medical Center+","correspondingAuthor":false,"prefix":"","firstName":"K.","middleName":"","lastName":"Winckers","suffix":""},{"id":527320712,"identity":"fdb50b26-b3b1-42f3-84e7-b61c2e4716f5","order_by":17,"name":"F. J.H. Magdelijns","email":"","orcid":"","institution":"Maastricht University Medical Centre","correspondingAuthor":false,"prefix":"","firstName":"F.","middleName":"J.H.","lastName":"Magdelijns","suffix":""}],"badges":[],"createdAt":"2025-09-05 08:53:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7542541/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7542541/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12877-026-06972-3","type":"published","date":"2026-01-23T15:58:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":93395203,"identity":"d4202d63-5bad-4fc6-938b-10f5daa06085","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"jpg","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65637,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/d2942945a280dfc2593072c5.jpg"},{"id":93396643,"identity":"4a006a35-eba5-4150-82f2-ed9d0725f859","added_by":"auto","created_at":"2025-10-13 11:43:14","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":784183,"visible":true,"origin":"","legend":"","description":"","filename":"Perspectivesinprescribmain.docx","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/2261af2ef15954abae03c724.docx"},{"id":93395205,"identity":"7e6260c8-372d-451e-b078-9b2931b055b0","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":13854,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/03d363a1fb57970a9aee5ea8.docx"},{"id":93395216,"identity":"9ebdbde1-33d8-4205-9273-24be6d7d73cc","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/e79f24d9173e56023eb7d4e8.tif"},{"id":93395214,"identity":"b440c582-77c6-4fac-a2ec-efe0d3e4063c","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"jpg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":56653,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/da9b4c2026ddd699067cc3a5.jpg"},{"id":93395743,"identity":"a2b677c5-1dcb-44b9-ae02-c73aac7026b9","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/ca00b0e0b7a835de64e2e3c5.tif"},{"id":93395728,"identity":"d69536bc-2e6b-473b-87a2-595d605bd167","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"jpg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":39792,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/c684de2ffac60f9c5c51d2c0.jpg"},{"id":93396928,"identity":"84f2ca03-7945-46b5-8163-0c21311b0470","added_by":"auto","created_at":"2025-10-13 11:51:14","extension":"tif","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/515b1772c12486a85263b324.tif"},{"id":93395739,"identity":"793d1f0f-7c25-42ce-8cdc-018d68fc70b3","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"jpg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73852,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/8542ff36f8d262c0853ac35d.jpg"},{"id":93395748,"identity":"5cf93370-d4ea-474d-8b25-2c62cbae6451","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"tif","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/0fc805a42b638c7e2aa5558f.tif"},{"id":93395735,"identity":"79da5669-cdad-447e-a5c9-c8c480a9d596","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"jpg","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":42058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/c87e48572c1003b01084fda5.jpg"},{"id":93395251,"identity":"82e586a8-b5a5-4e40-89e3-d5a82f078c0b","added_by":"auto","created_at":"2025-10-13 11:27:15","extension":"tif","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/73890128ed60314ff6fe5557.tif"},{"id":93396926,"identity":"9913b122-722c-44d5-9114-a479757e1fb8","added_by":"auto","created_at":"2025-10-13 11:51:14","extension":"json","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":18612,"visible":true,"origin":"","legend":"","description":"","filename":"439924d3436a4785bdeb2bbe982c6764.json","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/f0cdb202e9b31ce04833be5b.json"},{"id":93395223,"identity":"66692134-d87b-4218-8837-50f9f6bc710c","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"docx","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":16713,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYMATERIAL.docx","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/b0e5358803c84b7c60cac5a6.docx"},{"id":93395750,"identity":"514093c4-15a8-4b1f-86d8-cb5f4d42929c","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"xml","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":115895,"visible":true,"origin":"","legend":"","description":"","filename":"439924d3436a4785bdeb2bbe982c67641enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/f9b9badf795ea9ab2ad91866.xml"},{"id":93395219,"identity":"0bfc10a8-631b-4a06-b503-c2171ce713df","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"jpg","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65637,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/a65fe5cb978e23ff8c96d783.jpg"},{"id":93395250,"identity":"6a967d88-5ec8-4916-b69f-f4c8b5b0b74b","added_by":"auto","created_at":"2025-10-13 11:27:15","extension":"tif","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/9ad07f61a903f211848838bc.tif"},{"id":93396649,"identity":"4feb4786-918e-426b-8378-c25bf04b099d","added_by":"auto","created_at":"2025-10-13 11:43:14","extension":"jpg","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":56653,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/4fb2cc9e4334565015181fbe.jpg"},{"id":93395749,"identity":"dacf6f89-6575-4159-946d-1e14016daf88","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"tif","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure4.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/83e0545c773c3fc15e1d4d1d.tif"},{"id":93395217,"identity":"ec302271-8ffd-42e4-b044-81c7f0a4ac46","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"jpg","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":39792,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/34172db5e0b30dceb9161975.jpg"},{"id":93395759,"identity":"b9d07ab3-0081-493b-ae14-b6c50060a442","added_by":"auto","created_at":"2025-10-13 11:35:15","extension":"tif","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure5.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/a56173309c102662c5c1e19e.tif"},{"id":93395225,"identity":"4ad0eb4a-1a00-415c-a82a-337339b9fdb0","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"jpg","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73852,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/929c2f14c9434596d6100fe1.jpg"},{"id":93395231,"identity":"be0607a1-740f-4661-887e-fc700f4b6f94","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"tif","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/6822a9ae7b525e2783bad86e.tif"},{"id":93396650,"identity":"d465cfe8-9218-499c-9d76-80fa0bc9e0eb","added_by":"auto","created_at":"2025-10-13 11:43:14","extension":"jpg","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":42058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/80712c2e42755338a75792cd.jpg"},{"id":93395242,"identity":"d50fc27d-6393-4a2c-9fe4-1651c7ae4775","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"tif","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2765058,"visible":true,"origin":"","legend":"","description":"","filename":"Figure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/c17155a2cbe33857d52b731a.tif"},{"id":93395248,"identity":"e63ad6dc-029d-41dc-bf6e-6e7cff9700a2","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"png","order_by":25,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":147445,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/f62958624f6321306fe0fbfa.png"},{"id":93395240,"identity":"a1979a97-df19-4ce8-b18c-cb613a74ab5a","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"png","order_by":26,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":213733,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/bad0d51fa5cbbb0a600c8dc1.png"},{"id":93396655,"identity":"49f72f73-f3fc-4590-b962-6fadc2be5b20","added_by":"auto","created_at":"2025-10-13 11:43:14","extension":"png","order_by":27,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":125870,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/455f5ccc7ec3b53a4527139f.png"},{"id":93396656,"identity":"dbe1c43c-d3dc-4306-84e0-335c1cba3970","added_by":"auto","created_at":"2025-10-13 11:43:14","extension":"png","order_by":28,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101621,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/bd04a8ad4640bb242caca620.png"},{"id":93396653,"identity":"dc70cdf4-43fb-4c7d-92be-d7ee0d99a5f4","added_by":"auto","created_at":"2025-10-13 11:43:14","extension":"png","order_by":29,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":68889,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/52c0a1856c2d5265a7f0c760.png"},{"id":93395226,"identity":"712f0723-97d6-4aad-a522-e3541353aff6","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"png","order_by":30,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19523,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/0f4faf0acc711dc550658ed9.png"},{"id":93396661,"identity":"1f3d9f0f-ad03-4861-b95b-0c8e0ba06a92","added_by":"auto","created_at":"2025-10-13 11:43:15","extension":"png","order_by":31,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":15434,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/9854a06971759270a1d73a76.png"},{"id":93396927,"identity":"c4aba4ed-97a9-464c-af43-9f709d8eafec","added_by":"auto","created_at":"2025-10-13 11:51:14","extension":"png","order_by":32,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":10641,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure5.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/08401d6276a3771c00316136.png"},{"id":93395245,"identity":"20d3ad30-1618-41b0-954b-579df36b891b","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"png","order_by":33,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":21138,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/bad61d290bd017c762162717.png"},{"id":93396658,"identity":"39906e4c-e6c9-4b41-a9d6-a48dc5c6bf47","added_by":"auto","created_at":"2025-10-13 11:43:15","extension":"png","order_by":34,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":12838,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/418ac3e85474341bf8c7e5de.png"},{"id":93396660,"identity":"88611885-196c-4e66-984d-2e23180c8ade","added_by":"auto","created_at":"2025-10-13 11:43:15","extension":"png","order_by":35,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":20962,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/41982544f3ccf8dff5e0e2c0.png"},{"id":93395237,"identity":"c11ca4f7-0387-466d-8880-2bb32807d288","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"png","order_by":36,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19905,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/049c15e182c2768166cef7cd.png"},{"id":93395234,"identity":"122c3d1f-77ee-460d-8ed2-39404e08fd8b","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"png","order_by":37,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":19347,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/6442f3b7385483f6bc77774b.png"},{"id":93395238,"identity":"b2322947-9675-4594-93d3-2ef82df1f532","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"png","order_by":38,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":15258,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/38a2375f934eb0bb1048ae02.png"},{"id":93395773,"identity":"bb32822a-25dc-4fd9-b111-eb45f0a9f5c3","added_by":"auto","created_at":"2025-10-13 11:35:15","extension":"png","order_by":39,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":10641,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/8141a17e2703dd602d038e24.png"},{"id":93396929,"identity":"85623d16-504e-4df9-8a3d-0a651959ac07","added_by":"auto","created_at":"2025-10-13 11:51:15","extension":"xml","order_by":40,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":106665,"visible":true,"origin":"","legend":"","description":"","filename":"439924d3436a4785bdeb2bbe982c67641structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/4f72f49be9046651bc372d13.xml"},{"id":93395764,"identity":"930409be-ab29-4ebe-b3c4-2527e98308b1","added_by":"auto","created_at":"2025-10-13 11:35:15","extension":"html","order_by":41,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":128823,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/b47edb6b2e29d2eace1df8e1.html"},{"id":93395208,"identity":"81b95b53-efd4-419f-ae37-a7f512a116bb","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":73852,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003ePreferences of HCPs\u0026nbsp; for the type of anticoagulation based on patient characteristics and characteristics of anticoagulants\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: \u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e missing responses range between 0.3-7.9%\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/41a745e8b5b72beb46add3fa.jpg"},{"id":93395721,"identity":"f3a2bea8-e7f6-4b7e-97d6-5efdb5a74144","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42058,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHCPs responses regarding patient factors influencing the choice between DOAC and VKA\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: \u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e missing responses range between 0.3-0.6%\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/9b30a7bfe269a84b2668bc5e.jpg"},{"id":93395211,"identity":"2c591765-eb87-4ac6-b028-169523c997b9","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":65637,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHCPs responses regarding DOAC management\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/512c9677c1d19c6703c07582.jpg"},{"id":93395726,"identity":"86e5a45c-4f2e-4e2b-b76e-e30f8c6f733b","added_by":"auto","created_at":"2025-10-13 11:35:14","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":56653,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHCPs responses regarding DOAC level measurement\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/5fc0c3437e7c6463ff81a149.jpg"},{"id":93395213,"identity":"a3802aca-76e5-4ffa-a002-477e87a5e9d9","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":39792,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHCPs responses regarding evidence and recommendations for prescribing DOACs in frail older patients\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/2aaf7a89f6b1590b1b3359b4.jpg"},{"id":101152033,"identity":"b1ca170c-0582-4041-af31-97afb1a396c9","added_by":"auto","created_at":"2026-01-26 16:09:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":833507,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/95e3190d-c886-4ea7-80af-dca5463eb597.pdf"},{"id":93395207,"identity":"3e2ba98f-9783-4ba6-9bf7-0b1b1ad6139c","added_by":"auto","created_at":"2025-10-13 11:27:14","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16713,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYMATERIAL.docx","url":"https://assets-eu.researchsquare.com/files/rs-7542541/v1/9024608f153bddeebd21ce26.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eHealthcare Professionals' perspectives on prescribing DOACs to frail older patients; The DOAC-FRAIL questionnaire\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eDirect oral anticoagulants (DOACs) are increasingly prescribed by healthcare professionals (HCPs) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). DOACs are indicated for stroke prevention in atrial fibrillation (AF) and venous thromboembolism (VTE). Compared to vitamin K antagonists (VKAs), DOACs offer advantages such as ease of use, no need for laboratory monitoring and fewer interactions with food and drugs (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In the general patient population, DOACs have a reasonable efficacy and safety profile related to bleeding risk. Consequently, DOACs are also increasingly prescribed to frail older population. However, specifically in this population prescribers must consider drug-drug interactions, comorbidities, fall risk, medication adherence and increased thromboembolic and bleeding risks. There is increasing evidence that DOACs should be prescribed with caution in frail older patients. First, the randomized controlled FRAIL-AF trial indicated a 69% increased risk of major bleeding and clinically relevant non-major bleeding when switching from a VKA to a DOAC in a frail older patient with AF (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Second, our previous study has shown that DOAC levels measured during an acute hospital admission were outside the expected range in more than half of frail older patients (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Furthermore, unusual high intra-individual variability in DOAC levels have been identified in the same population (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). These findings indicate the need to critically re-evaluate both the prescribing criteria for DOACs in the frail older population and the implementation strategies required to ensure their safe and effective use.\u003c/p\u003e\u003cp\u003eKnowledge on how prescribers currently approach the prescription of DOACs to frail older patients is lacking. However, given the concerns outlined above, gaining insights into current prescribing practices is essential for the development of uniform guidelines for the use of DOACs in the frail older population. To explore this, we conducted a cross-sectional international study using an online questionnaire among HCPs .\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cem\u003eDESIGN AND POPULATION\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn this cross-sectional study, an online questionnaire was distributed among HCPs in the Netherlands and Belgium. This survey was developed by a team of five researchers with established expertise in the field of direct oral anticoagulants (DOACs) and the clinical management of frail older adults, in order to ensure both content validity and clinical relevance.\u0026nbsp;The questionnaire was available in Dutch and French. An English version of the questionnaire is available as Supplementary Material. Since our focus was on DOAC use within the frail older population (age\u0026nbsp;\u0026ge;70 years, Clinical Frailty Scale \u0026gt;5), the questionnaire was distributed to general practitioners, geriatricians, cardiologists, elderly care physicians(10) and physician assistants (last two are only applicable in the Netherlands), between April 2024 and January 2025. Distribution was primarily through a QR code or web link presented in newsletters of the medical associations involved, e.g. the Dutch Society of Internal Medicine (NIV), the Dutch Geriatrics Society (NVKG), the Dutch society of cardiology (NVVC), Healthcare in development (ZIO), the Belgian Society of Cardiology (BSC), the Dutch Association of Elderly Care Physicians Verenso), the Dutch society of Physician Assistants (NAPA), the Belgian Society of Gerontology and Geriatrics (BSGG), and General Physician society Domus Medica (LHV) with secondary distribution allowed through peer-to-peer sharing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eETHICS APROVAL AND CONSENT TO PARTICIPATE\u003c/p\u003e\n\u003cp\u003eThe medical ethics committee (METC) of the MUMC+ assessed the study and concluded that due to the nature of the study it does not fall under the scope of the Medical Research Involving Human Subjects Act (METC number 2021-2945). This study did not involve patient data or interventions Healthcare professionals (HCPs) were invited to participate on a voluntary basis. The survey was primarily distributed via a QR code or web link included in newsletters from the participating medical associations. Upon accessing the survey, HCPs were presented with a brief introduction outlining the purpose of the study, the voluntary nature of participation, the content of the survey, and the intended use of aggregated results for analysis and publication. Formal written informed consent was not required in accordance with applicable regulations, as completion of the survey was taken as implicit consent.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDATA COLLECTION\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA web-based, secure software platform (Qualtrics XM) was used to build and distribute the questionnaire, followed by data collection and data-management.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe statements and questions primarily focused on exploring prescribing behavior, managing and monitoring of DOAC therapy, and aimed to gain insight into the perceived knowledge in terms of available evidence and guideline recommendations for prescribing and managing DOAC use in frail older patients. The questionnaire was developed by the research team, based on existing literature, prior research experience, clinical experience and the findings from the previous conducted DOAC-FRAIL studies (6, 7).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe questionnaire comprised 27 items across three sections. The first section included 5 questions on HCP demographics. The second section consisted of 16 statements and the third section contained 6 multiple-choice questions, both focusing on the prescription of anticoagulants, in particular DOACs, in frail older patients (S1). The themes evaluated were: (1) factors influencing the choice of anticoagulant (DOAC, VKA or low molecular weight heparin (LMWH)), (2) DOAC management approaches, (3) need for and use of DOAC level measurements, and (4) awareness of DOAC management guidelines and available evidence. HCPs were asked to rate the 16 statements on a 5-point Likert scale, with response options ranging from \u0026ldquo;always\u0026rdquo; to \u0026ldquo;never\u0026rdquo; and \u0026ldquo;strongly agree\u0026rdquo; to \u0026ldquo;strongly disagree\u0026rdquo;(11). At various points, respondents were given the opportunity to share reflections, comments or questions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSTATISTICS\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eQuestionnaires were collected in Qualtrics XM and exported to IBM Statistical Package for Social Sciences (SPSS) version 28 for analysis. Descriptive statistics were applied to all quantitative results. The open-text comments were analyzed, categorized and textually summarized by one researcher.\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cem\u003eRESPONDENTS DEMOGRAPHICS\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA total of 355 HCPs completed the questionnaire (Table 1 and S1). Most HCPs were based in a hospital (54.0%), followed by 24.2% working in \u0026nbsp;general practice settings and 19.2% working in a nursing home (19.2%). The majority of HCPs was between 30 and 44 years of age (49.3%) (S2).\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"702\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 702px;\"\u003e\n \u003cp\u003e\u003cem\u003eTable 1. Demographics \u0026nbsp;(n= 355)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 316px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedical specialty:\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eGeriatrician\u003c/p\u003e\n \u003cp\u003eCardiologist\u003c/p\u003e\n \u003cp\u003eElderly care physician\u003c/p\u003e\n \u003cp\u003eGeneral practitioner\u003c/p\u003e\n \u003cp\u003ePhysician assistant\u003c/p\u003e\n \u003cp\u003eOther**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 386px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e93 (26.2%), in training 19 (5.4%)\u003c/p\u003e\n \u003cp\u003e58 (16.3%), in training 10 (2.8%)\u003c/p\u003e\n \u003cp\u003e59 (16.6%), in training 16 (4.5%)\u003c/p\u003e\n \u003cp\u003e80 (22.5%), in training 5 (1.4%)\u003c/p\u003e\n \u003cp\u003e10 (2.8%)\u003c/p\u003e\n \u003cp\u003e5 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 316px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHealthcare facility:\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eUniversity hospital\u003c/p\u003e\n \u003cp\u003ePeripheral hospital\u003c/p\u003e\n \u003cp\u003eNursing home\u003c/p\u003e\n \u003cp\u003eGeneral practice\u003c/p\u003e\n \u003cp\u003eOther***\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 386px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58 (16.3%)\u003c/p\u003e\n \u003cp\u003e134 (37.7%)\u003c/p\u003e\n \u003cp\u003e68 (19.2%)\u003c/p\u003e\n \u003cp\u003e86 (24.2%)\u003c/p\u003e\n \u003cp\u003e6 (1.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 316px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge group:\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e25-29 years\u003c/p\u003e\n \u003cp\u003e30-34 years\u003c/p\u003e\n \u003cp\u003e35-39 years\u003c/p\u003e\n \u003cp\u003e40-44 years\u003c/p\u003e\n \u003cp\u003e45-49 years\u003c/p\u003e\n \u003cp\u003e50-54 years\u003c/p\u003e\n \u003cp\u003e55-59 years\u003c/p\u003e\n \u003cp\u003e60-64 years\u003c/p\u003e\n \u003cp\u003e65-70 years\u003c/p\u003e\n \u003cp\u003eOther****\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 386px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32 (9.0%)\u003c/p\u003e\n \u003cp\u003e70 (19.7%)\u003c/p\u003e\n \u003cp\u003e66 (18.6%)\u003c/p\u003e\n \u003cp\u003e39 (11.0%)\u003c/p\u003e\n \u003cp\u003e30 (8.5%)\u003c/p\u003e\n \u003cp\u003e40 (11.3%)\u003c/p\u003e\n \u003cp\u003e34 (9.6%)\u003c/p\u003e\n \u003cp\u003e24 (6.8%)\u003c/p\u003e\n \u003cp\u003e10 (2.8%)\u003c/p\u003e\n \u003cp\u003e10 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 316px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWork experience:\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0-5 years\u003c/p\u003e\n \u003cp\u003e6-10 years\u003c/p\u003e\n \u003cp\u003e11-15 years\u003c/p\u003e\n \u003cp\u003e\u0026ge;\u0026nbsp;16 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 386px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e83 (23.4%)\u003c/p\u003e\n \u003cp\u003e83 (23.4%)\u003c/p\u003e\n \u003cp\u003e59 (16.6%)\u003c/p\u003e\n \u003cp\u003e129 (36.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 702px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e** Gastroenterologist, cardiac surgeon and clinical pharmacologist\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e*** Private clinic and rehabilitation center\u003cbr\u003e\u0026nbsp;**** Age was not specified in additional remarks\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eT\u003cem\u003eHEME (1) FACTORS INFLUENCING THE CHOICE FOR ANTICOAGULATION TYPE\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn very old (\u0026gt;80 years) patients, patients with cognitive impairment and in frail patients, most HCPs prefer prescribing a DOAC instead of VKA or LWMH. When selecting an anticoagulant for the oldest patients (\u0026gt;80 years), key considerations included the absence of a need for laboratory based dose adjustments (need for monitoring) (n=263, 74,1%), adherence (n=168, 47.3%), efficacy (n=154, 43.4%) and side effects (n= 147, 41.1%), with these factors once again favoring the use of DOACs. When selecting an anticoagulant for patients with cognitive impairment, HCPs reported that their decisions were primarily influenced by the absence of a need for laboratory based dose adjustments (n=295, 73.0%), followed by medication adherence (n=188, 53.0%), efficacy (n=128, 36.1%) and side-effects (n=123, 34.6%). Comparable factors influenced anticoagulant selection in frail patients, with similar emphasis on the absence of a need for laboratory based dose adjustments (n=274, 77.2%), adherence (n=174, 49.0%), efficacy (n=153, 43.1%), and side-effects (n=140, 39.4%). Figure 1 illustrates the responses to the multiple-choice questions related to the choice of DOAC, VKA, or LMWH as anticoagulant options.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlong with the previously mentioned factors, healthcare professionals were asked whether, based on their experience, a specific anticoagulant (DOAC, VKA, or LMWH) affected the occurrence of bleeding complications in frail older patients (missing data 7.9%): HCPs predominantly observed fewer bleeding complications with DOACs (81.4%) than with VKA (10.7%) or LMWH (0.0%).\u003c/p\u003e\n\u003cp\u003eThe majority of HCPs considered frailty (often 39.2%, always 17.7%), cognitive function (often 26.8%, always 13.2%), and the risk of falls (often 31.3%, always 15.8%) when making this decision. However, age was a factor that most HCPs did not prioritize when choosing between DOACs and VKAs, with 29.3% rarely considering it and 27.9% never considering it. An significant percentage of respondents actively switched from VKA to DOAC in frail older patients (often 37.7%, always 8.7% versus never 7.6%, rarely 22.8%). Figure 2 presents four statements outlining factors influencing the decision between DOACs and VKA.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eComments of HCPs\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA small number of respondents (n=16) commented that a switch from a VKA to a DOAC was typically made when the INR was unstable or when issues arose with obtaining INR measurements. Additionally, \u0026nbsp;few respondents (n=13) reported switching from a VKA to a DOAC less often following the FRAIL-AF study (5). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTHEME (2) DOAC MANAGEMENT APPROACHES\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe majority of HCPs preferred apixaban (56.6%) as DOAC in frail older patients (rivaroxaban 9.6%, edoxaban 16.9%, dabigatran 1.4% and no preference 14.9%). Most of the respondents \u0026nbsp;did not choose a dose reduction because of frailty (never 30.4%, rarely 37.2%), regardless of renal function and/or weight (Figure 3). More than half of HCPs reported conducting annual evaluation of adherence/compliance, complications, and renal function when prescribing DOACs (annual weighing consultation), with 30.4% doing so frequently and 37.2% always. In contrast, 2.8% indicated they never, 13.5% rarely conducted this annual evaluation, and 15.8% remained neutral on the matter. Additionally, the majority of HCPs checked at each patient contact if the DOAC dose was still in line with recommendations for renal function and made adjustments when necessary.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe vast majority of HCPs considered DOACs as beneficial for the frail older population, due to fixed-dose prescription and no need for laboratory based dose adjustments (agree 46.8%, strongly agree 36.3%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTHEME (3) NEED FOR AND USE OF DOAC LEVEL MEASUREMENTS\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHCPs did not determine a DOAC level often (rarely 18.3%) and most HCPs do not measure a DOAC level at all (never 74.9% versus often 0.0% and always 1.7%). In addition, HCPs did not often adjust dosage based on the DOAC level (never 67.6%, rarely 11.8% versus 0.6%, always 1.7%) (Figure 4). During acute hospitalization HCPs very rarely measured a DOAC level (never 52.4%, rarely 10.4% versus often 0.6, always 0.30%). 56.9% of HCPs were assured that when using a DOAC in frail older patients, DOAC levels would be within the expected range (on-therapy) despite the absence of monitoring (often 38.9%, always 18%). When asked specifically about the reason for DOAC level measurement (when measured), 25.4% (n=90) indicated that this was performed because of bleeding and 24.8% (n=88) because of thrombosis under DOAC use. Other reasons included acute renal impairment, evaluation of efficacy, a history of \u0026nbsp;a gastric bypass or the need for surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTHEME (4) DOAC MANAGEMENT GUIDELINES AND AVAILABLE EVIDENCE\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e20.0% of HCPs stated that there was insufficient evidence for safe prescription of DOACs in the frail older population (agree 17.7%, strongly agree 2.3%). Furthermore, 77.7% of HCPs indicated that there should be clearer recommendations regarding DOAC management in this specific population (strongly agree 19.7%, agree 58.0%; Figure 5). \u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study provides new insights into oral anticoagulant prescribing behavior of HCPs to frail older patients. First, HCPs (in general) preferred DOACs over VKAs. Second, the study found that cognitive impairment, fall risk and frailty were all key factors considered when determining for the appropriate type of anticoagulation treatment, while age was not. In addition, the primary reasons HCPs preferred DOACs over VKA were no need for monitoring and medication adherence. Notably, 46.4% of HCPs actively converted patients from VKA to DOAC, although additional comments suggested that several HCPs have abandoned this practice since the publication of the FRAIL-AF study (5). Fourth, an important observation was that only 67.6% of HCPs performed an annual treatment assessment in frail older patients using DOACs. In addition, the vast majority of HCPs did not measure DOAC levels in this specific population, while only 56.9% of HCPs expressed confidence that DOAC levels would be within the expected range. Lastly, a significant portion of HCPs expressed the need for explicit recommendations regarding DOAC therapy in frail older patients.\u003c/p\u003e\n\u003cp\u003eHCPs favored DOACs for frail, cognitively impaired patients or patients at risk of falls. The preference for DOACs aligns with evidence suggesting they offer advantages over VKAs such as reduced need for laboratory drug level monitoring and fewer food interactions (12). However, literature shows \u0026nbsp;growing awareness of issues such as poor medication adherence (13), the impact of polypharmacy (4, 14), \u0026nbsp; comorbidities (15) and renal failure in relation to DOAC use (16). Moreover, the underrepresentation of frail older adults in major clinical trials complicates anticoagulant selection and limits the applicability of trial results to real-world practice. Interestingly, despite the preference for DOACs, our survey revealed reservations about switching from VKAs to DOACs. This finding echoes concerns raised by the recent randomized FRAIL-AF study, which indicated an increased risk of major and clinically relevant non-major bleeding complications in frail older patients when switching from VKAs to DOACs (5). In line with the aforementioned, the recently updated guidelines for the management of atrial fibrillation by the European Society of Cardiology, developed in collaboration with the European Association for Cardio-Thoracic Surgery, recommend that frail patients aged 75 years or older who are on polypharmacy and stable on a VKA continue VKA therapy rather than switch to a DOAC (17). Thus, while DOACs are considered an appropriate choice for the frail older population, HCPs should be increasingly cautious about making active switches, particularly in light of bleeding risks. Further research is warranted to determine whether the \u0026lsquo;one-size-fits-all\u0026rsquo; approach of DOAC prescribing is truly appropriate and safe for this population.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHCPs\u0026rsquo; preference for apixaban as the most suitable DOAC for frail older patients is consistent with existing literature, which highlights the drug\u0026apos;s favorable pharmacokinetic profile and lower bleeding risk compared to other DOACs such as rivaroxaban or edoxaban (18). In addition, many HCPs adjust dosages based on age and/or frailty , and not solely based on renal function or weight (19). Recent findings display benefits of reduced doses in older adults with multimorbidity (20).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnnual weighing consultation was acknowledged by only 67.6% of the respondents, which is concerning. The issue of monitoring is a critical aspect of anticoagulation management. The 2018 European Heart Rhythm Association (EHRA) guidelines concluded that DOAC treatment requires vigilance due to potentially severe complications, particularly as the target patient population tends to be of older age and frail (19). In patients aged \u0026ge;75 and/or with increased frailty, blood tests evaluating hemoglobin, liver function and renal function are recommended at least every 6 months (19).\u0026nbsp; The 2021 practical guide on the use of non-vitamin K antagonist oral anticoagulants (EHRA) strongly advises a regular weighing consultation for patients with renal failure, older age, comorbidities, frailty or cognitive decline. Follow-up should include evaluation of adherence, thromboembolic events, bleeding events, side effects, co-medication, need for blood sampling, modifiable risk factors and optimal DOAC and correct dosing (21). To facilitate this, recent studies suggest reassessing the role of anticoagulation clinics to monitor patients on DOACs, similar to the approach used for those on VKAs (22-24). The low number of HCPs performing these weighing consultations is possibly due to a paucity in implementing these guidelines.\u003c/p\u003e\n\u003cp\u003eHCPs did not or very rarely measure DOAC levels. Even in acute situations or during hospitalization, DOAC levels were not or rarely measured by HCPs. Interestingly, only 56.9% were convinced that DOAC levels would be within the on-therapy range when used in frail older patients. Not measuring DOAC levels may, for a large part, reflect lack of availability and/or knowledge about indications for DOAC level testing or is a consequence of an cost-effectiveness assessment. It may also be linked to the notion that DOACs, unlike VKAs, generally do not require regular dose adjustment for optimizing therapeutic efficacy. Furthermore, there is a lack of information regarding the clinical consequences of deviant levels under medically stable conditions. However, elevated levels have been associated with an increased risk of bleeding, while lower levels are linked to a higher risk of thrombosis(25-28). The International Council for Standardization in Haematology recommends the option of DOAC level testing in patients with advanced age, severe renal failure, high body mass index, drug interactions or prior to an intervention with high bleeding risk (29). \u0026nbsp;In contrast, the EHRA guidelines recommend measuring DOAC levels in emergency situations such as bleeding, stroke or overdose, as well as in medication interactions, extremes in body weight and renal impairment (21). ESC guidelines recommend measurements in the presence of stroke or bleeding conditions and the need for acute surgery only (17). In addition, in cases of acute life-threatening bleeding, when reversal agents are being considered, measuring DOAC levels is advised to assess the contribution of the DOAC and to support decision-making for interventions (30). The infrequent measurement of DOAC levels by HCPs during acute hospitalizations warrants further investigation, as recent studies suggest that DOAC level measurements could be beneficial in improving the management of patients with acute conditions or complications (29, 31).\u003c/p\u003e\n\u003cp\u003eImportantly, this study revealed that of HCPs (20.0%) stated that there was insufficient evidence to support the prescription of DOACs in the frail older population. In addition, a substantial number of HCPs expressed the need for clearer recommendations and guidelines specifically tailored to frail older patients. The desire for more evidence and specific recommendations reflects the broader clinical uncertainty regarding the optimal approach to DOAC use in frail, older patients, as well as the challenges HCPs face in balancing the associated benefits and risks. This underscores a critical gap in clinical knowledge and emphasizes the need for further research, particularly randomized controlled trials, focusing on the safety and efficacy of DOACs in this population, serving as a first step toward developing tailored recommendations in clinical guidelines.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe current study has noteworthy strengths. First, the questionnaire was specifically focused on DOAC treatment in frail older patients, addressing a diverse group of HCPs, including those working in university and non-university hospitals, nursing homes, and general practice clinics. Second, this is the first study to provide insight into the use of DOAC level measurements in daily practice by HCPs, as well as to address the need for tailored guidelines for the frail older population. A limitation of the study is the inability to calculate the response rate due to several factors: (1) no data was available on the exact number of members receiving the newsletter from the relevant professional associations, (2) HCPs may have received the survey through multiple associations, and (3) it was allowed to distribute the survey via peer-to-peer channels. However, a total of 355 HCPs completed the survey, representing a relatively large group of participants. Another limitation of the study is that the design and method of survey distribution may limit the generalizability of the findings to other healthcare systems in Europe and beyond.\u0026nbsp;\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn conclusion, this study provides valuable insights into the complex decision-making process surrounding the use of DOACs in frail older patients. In short, HCPs do not follow a uniform approach when prescribing and managing DOACs in frail older patients. In addition, a significant proportion of HCPs are seeking for tailored recommendations in international guidelines. Thus, there is a need for further research on DOAC management in this specific population with the goal of ensuring safer use of DOACs and providing clinically applicable recommendations in guidelines.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eF. Magdelijns and M. de Jong conceived the study. F. Magdelijns, M. de Jong, S. Robben, D. Janssen and A. Brys contributed to the design of the study and drafting the questionnaire. All authors helped distribute the questionnaire to DOAC prescribing healthcare professionals. F. Magdelijns and M. de Jong collected all data. F. Magdelijns, A. Brys, H. ten Cate, K. Winckers and M. de Jong contributed to the interpretation of the data. M. de Jong wrote the manuscript. F. Magdelijns, A. Brys. K. Winckers and H. ten Cate revised the manuscript. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures:\u0026nbsp;\u003c/strong\u003eHtC received research support from Astra Zeneca and consulting fees from Astra Zeneca, Galapagos, Alveron and Novostia. He is shareholder of CoagulationProfile, a spinoff diagnostic company from Maastricht University. All revenues are deposited at the CARIM institute for research purposes. He is a former chairman of board of the Dutch Federation of Anticoagulation clinics, which is a pro deo position. RDC received consultancy/speakers fees from Sanofi, Milestone, Daiichi-Sankyo, Janssen, Pfizer, Bristol-Myers Squibb, Menarini, and Amarin, travel support from Amarin and Daiichi-Sankyo, and participated in the Data Safety Monitoring Board of NOAH-AFNET6 (Daiichi- Sankyo), all outside this project. In addition, he is member of the Editorial Board of European Heart Journal. DJAJ received lecture fees from Chiesi, AstraZeneca and Abbott within the past three years, all paid to the institution and outside the submitted work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSponsor\u0026rsquo;s Role:\u003c/strong\u003e There was no funding or sponsor\u0026apos;s role in the design, methods, subject recruitment, data collection, analysis, or preparation of the paper.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe dataset used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWheelock KM, Ross JS, Murugiah K, Lin Z, Krumholz HM, Khera R. Clinician Trends in Prescribing Direct Oral Anticoagulants for US Medicare Beneficiaries. JAMA Netw Open. 2021;4(12):e2137288.\u003c/li\u003e\n\u003cli\u003ede Vries TAC, Bavalia R, Chu G, Xiong H, van de Wiel KM, van Ballegooijen H, et al. Prescription and switching patterns of direct oral anticoagulants in patients with atrial fibrillation. Research and Practice in Thrombosis and Haemostasis. 2024;8(6):102544.\u003c/li\u003e\n\u003cli\u003eZeng S, Zheng Y, Jiang J, Ma J, Zhu W, Cai X. Effectiveness and Safety of DOACs vs. Warfarin in Patients With Atrial Fibrillation and Frailty: A Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2022;9:907197.\u003c/li\u003e\n\u003cli\u003eFerri N, Colombo E, Tenconi M, Baldessin L, Corsini A. Drug-Drug Interactions of Direct Oral Anticoagulants (DOACs): From Pharmacological to Clinical Practice. Pharmaceutics. 2022;14(6).\u003c/li\u003e\n\u003cli\u003eJoosten LPT, van Doorn S, van de Ven PM, K\u0026ouml;hlen BTG, Nierman MC, Koek HL, et al. Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial. Circulation. 2024;149(4):279-89.\u003c/li\u003e\n\u003cli\u003ede Jong MJ, Saadan H, Hellenbrand DLS, Ten Cate H, Spaetgens B, Br\u0026uuml;ggemann RAG, et al. The DOAC-FRAIL study, evaluation of direct oral anticoagulant-levels in acutely admitted frail older patients: An exploratory study. J Am Geriatr Soc. 2024;72(7):2249-53.\u003c/li\u003e\n\u003cli\u003ede Jong MJ, Saadan H, van der Hooft BHM, Hellenbrand DLS, Br\u0026uuml;ggemann RAG, Ten Cate H, et al. Intra-Individual Variability of Direct Oral Anticoagulant Levels in Frail Older Patients upon, during, and after Acute Hospitalization: the DOAC-FRAIL Study. J Am Med Dir Assoc. 2024;25(12):105280.\u003c/li\u003e\n\u003cli\u003eToorop MMA, van Rein N, Nierman MC, Vermaas HW, Huisman MV, van der Meer FJM, et al. Inter- and intra-individual concentrations of direct oral anticoagulants: The KIDOAC study. J Thromb Haemost. 2022;20(1):92-103.\u003c/li\u003e\n\u003cli\u003eTesta S, Tripodi A, Legnani C, Pengo V, Abbate R, Dellanoce C, et al. Plasma levels of direct oral anticoagulants in real life patients with atrial fibrillation: Results observed in four anticoagulation clinics. Thrombosis Research. 2016;137:178-83.\u003c/li\u003e\n\u003cli\u003eKoopmans RT, Lavrijsen JC, Hoek JF, Went PB, Schols JM. Dutch elderly care physician: a new generation of nursing home physician specialists. J Am Geriatr Soc. 2010;58(9):1807-9.\u003c/li\u003e\n\u003cli\u003eLikert R. A technique for the measurement of attitudes. Archives of Psychology. 1932.\u003c/li\u003e\n\u003cli\u003eChen A, Stecker E, B AW. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. J Am Heart Assoc. 2020;9(13):e017559.\u003c/li\u003e\n\u003cli\u003eSalmasi S, Safari A, Kapanen A, Adelakun A, Kwan L, MacGillivray J, et al. Oral anticoagulant adherence and switching in patients with atrial fibrillation: A prospective observational study. Res Social Adm Pharm. 2022;18(11):3920-8.\u003c/li\u003e\n\u003cli\u003eHarskamp RE, Teichert M, Lucassen WAM, van Weert H, Lopes RD. Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation. Cardiovasc Drugs Ther. 2019;33(5):615-23.\u003c/li\u003e\n\u003cli\u003eKajy M, Mathew A, Ramappa P. Treatment Failures of Direct Oral Anticoagulants. Am J Ther. 2021;28(1):e87-e95.\u003c/li\u003e\n\u003cli\u003eHahn K, Lamparter M. Prescription of DOACs in Patients with Atrial Fibrillation at Different Stages of Renal Insufficiency. Adv Ther. 2023;40(10):4264-81.\u003c/li\u003e\n\u003cli\u003eVan Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns H, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314-414.\u003c/li\u003e\n\u003cli\u003eKim DH, Pawar A, Gagne JJ, Bessette LG, Lee H, Glynn RJ, et al. Frailty and Clinical Outcomes of Direct Oral Anticoagulants Versus Warfarin in Older Adults With Atrial Fibrillation : A Cohort Study. Ann Intern Med. 2021;174(9):1214-23.\u003c/li\u003e\n\u003cli\u003eSteffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(16):1330-93.\u003c/li\u003e\n\u003cli\u003eHayes KN, Zhang T, Kim DH, Daiello LA, Lee Y, Kiel DP, et al. Benefits and Harms of Standard Versus Reduced\u0026amp;#x2010;Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation. Journal of the American Heart Association. 2023;12(21):e029865.\u003c/li\u003e\n\u003cli\u003eSteffel J, Collins R, Antz M, Cornu P, Desteghe L, Haeusler KG, et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021;23(10):1612-76.\u003c/li\u003e\n\u003cli\u003eTripodi A, Chantarangkul V, Poli D, Testa S, Bucciarelli P, Peyvandi F. The role of anticoagulation clinics needs to be reassessed to include follow up of patients on direct oral anticoagulants. Thromb Res. 2023;225:11-5.\u003c/li\u003e\n\u003cli\u003eSylvester KW, Chen A, Lewin A, Fanikos J, Goldhaber SZ, Connors JM. Optimization of DOAC management services in a centralized anticoagulation clinic. Res Pract Thromb Haemost. 2022;6(3):e12696.\u003c/li\u003e\n\u003cli\u003eAlbert V, Baumgartner PC, Hersberger KE, Arnet I. How do elderly outpatients manage polypharmacy including DOAC - A qualitative analysis highlighting a need for counselling. Res Social Adm Pharm. 2022;18(6):3019-26.\u003c/li\u003e\n\u003cli\u003eReilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014;63(4):321-8.\u003c/li\u003e\n\u003cli\u003eRuff CT, Giugliano RP, Braunwald E, Morrow DA, Murphy SA, Kuder JF, et al. Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet. 2015;385(9984):2288-95.\u003c/li\u003e\n\u003cli\u003eTesta S, Paoletti O, Legnani C, Dellanoce C, Antonucci E, Cosmi B, et al. Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost. 2018;16(5):842-8.\u003c/li\u003e\n\u003cli\u003eTesta S, Legnani C, Antonucci E, Paoletti O, Dellanoce C, Cosmi B, et al. Drug levels and bleeding complications in atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost. 2019;17(7):1064-72.\u003c/li\u003e\n\u003cli\u003eDouxfils J, Adcock DM, Bates SM, Favaloro EJ, Gouin-Thibault I, Guillermo C, et al. 2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants. Thromb Haemost. 2021;121(8):1008-20.\u003c/li\u003e\n\u003cli\u003eSpecialisten FvM. Antitrombotisch beleid. 2021-2025.\u003c/li\u003e\n\u003cli\u003eAhuja T, Raco V, Bhardwaj S, Green D. To Measure or Not to Measure: Direct Oral Anticoagulant Laboratory Assay Monitoring in Clinical Practice. Adv Hematol. 2023;2023:9511499.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Thrombosis Frail, older patients, DOAC, Prescribing behavior","lastPublishedDoi":"10.21203/rs.3.rs-7542541/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7542541/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\n\u003cp\u003eDOACs are increasingly prescribed for atrial fibrillation and venous thromboembolism due to their ease of use and lack of monitoring requirements. Prescribing DOACs to frail older patients remains challenging due to higher bleeding and thrombo-embolic risks, comorbidities, polypharmacy, and underrepresentation in clinical trials. This study explored prescribing behavior of healthcare professionals (HCPs) in this complex clinical context.\u003c/p\u003e\n\u003cp\u003eMethods\u003c/p\u003e\n\u003cp\u003eAn online questionnaire was distributed to HCPs involved in the care of frail older patients. The survey consisted of 27 items divided into three sections: demographics, factors influencing anticoagulant choice, and DOAC management. Descriptive statistics were used to evaluate outcomes.\u003c/p\u003e\n\u003cp\u003eResults\u003c/p\u003e\n\u003cp\u003e355 HCPs completed the questionnaire. HCPs considered frailty(56.9%), fall risk(47.1%) and cognitive impairment (40.0%) when choosing an anticoagulant. Apixaban was the preferred DOAC(56.6%). 74.9% of HCPs did not measure DOAC levels in clinically stable patients, whereas 62.8% measured DOAC levels during acute hospitalizations. A large group of HCPs(46.4%) actively switched from VKA to DOAC, but expressed reservations due to fear for an increased bleeding risk. Almost half(48.1%) of HCPs indicated the need for clearer, tailored guidelines for DOAC use in frail older patients.\u003c/p\u003e\n\u003cp\u003eConclusions\u003c/p\u003e\n\u003cp\u003eThis study highlights the complexity of prescribing DOACs to frail older patients. While HCPs take multiple factors into account, a standardized approach to prescribing DOACs in this population remains lacking. In addition, almost half of HCPs expressed a need for guidelines regarding DOAC use in frail older patients. Hence, more research is needed to fill this knowledge gap and guide HCPs in clinical practice.\u003c/p\u003e","manuscriptTitle":"Healthcare Professionals' perspectives on prescribing DOACs to frail older patients; The DOAC-FRAIL questionnaire","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-13 11:27:09","doi":"10.21203/rs.3.rs-7542541/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-13T04:10:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-03T07:58:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-27T07:16:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-25T12:26:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164387478256255845673129606976254231396","date":"2025-10-23T02:41:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"172319561211422095840665052582075710406","date":"2025-10-01T22:41:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300510833443241787277206079239943238826","date":"2025-09-29T22:51:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-29T21:54:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-23T06:54:42+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-23T06:36:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-22T07:18:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Geriatrics","date":"2025-09-22T07:13:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"018f1856-cbf6-4393-b137-6b670027b594","owner":[],"postedDate":"October 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:05:05+00:00","versionOfRecord":{"articleIdentity":"rs-7542541","link":"https://doi.org/10.1186/s12877-026-06972-3","journal":{"identity":"bmc-geriatrics","isVorOnly":false,"title":"BMC Geriatrics"},"publishedOn":"2026-01-23 15:58:32","publishedOnDateReadable":"January 23rd, 2026"},"versionCreatedAt":"2025-10-13 11:27:09","video":"","vorDoi":"10.1186/s12877-026-06972-3","vorDoiUrl":"https://doi.org/10.1186/s12877-026-06972-3","workflowStages":[]},"version":"v1","identity":"rs-7542541","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7542541","identity":"rs-7542541","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}