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.

BACKGROUND: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC). METHODS: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL·min-1·1.73 m-2 or with valvular atrial fibrillation were excluded. Follow-up was 12 months. The cause-specific hazard ratio was calculated for occurrence of the primary outcome that was a major or clinically relevant nonmajor bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events. RESULTS: Between January 2018 and June 2022, a total of 2621 patients were screened for eligibility and 1330 patients were randomly assigned (mean age 83 years, median Groningen Frailty Indicator score 4). After randomization, 6 patients in the switch-to-NOAC arm and 1 patient in the continue-with-VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to an NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The hazard ratio for our primary outcome was 1.69 (95% CI, 1.23-2.32). The hazard ratio for thromboembolic events was 1.26 (95% CI, 0.60-2.61). CONCLUSIONS: Switching international normalized ratio-guided VKA treatment to an NOAC in frail older patients with atrial fibrillation was associated with more bleeding complications compared with continuing VKA treatment, without an associated reduction in thromboembolic complications. REGISTRATION: URL: https://eudract.ema.europa.eu; Unique identifier: 2017-000393-11. URL: https://eudract.ema.europa.eu; Unique identifier: 6721 (FRAIL-AF study).

Cognitive screening and rehabilitation after cardiac arrest: only a few hurdles to take.

Dutch and European guidelines recommend systematic screening for cognitive and emotional impairments in cardiac arrest survivors. We aimed to clarify opinions on cognitive screening and rehabilitation, identify barriers and facilitators for implementation in the Netherlands, and arrive at recommendations in this field. We conducted 22 semi-structured interviews with various stakeholders using the Tailored Implementation in Chronic Diseases checklist. There is broad-based acknowledgement of the relevance of cognitive impairment and a positive attitude regarding early cognitive screening among health professionals and patients. Barriers to implementation include a lack of practical recommendations on how, where and when to screen, insufficient knowledge of cognitive consequences of cardiac arrest, insufficient collaboration and knowledge sharing among different specialties within hospitals, insufficient resources, and insufficient evidence of the effectiveness of screening and therapy to justify financial compensation. Most of the identified barriers to implementation are solvable: national guidelines need practical recommendations and knowledge gaps among healthcare workers can be bridged by in-hospital collaboration. Fulfilling these requirements should be sufficient for the implementation of simple screening and tailored advice. More extensive cognitive rehabilitation therapy needs stronger evidence of efficacy in order to warrant stronger guideline recommendations and financial reimbursement.

Design of the Dutch multicentre study on opportunistic screening of geriatric patients for atrial fibrillation using a smartphone PPG app: the Dutch-GERAF study.

BACKGROUND: Screening of high-risk patients is advocated to achieve early detection and treatment of clinical atrial fibrillation (AF). The Dutch-GERAF study will address two major issues. Firstly, the effectiveness and feasibility of an opportunistic screening strategy for clinical AF will be assessed in frail older patients and, secondly, observational data will be gathered regarding the efficacy and safety of oral anticoagulation (OAC). METHODS: This is a multicentre study on opportunistic screening of geriatric patients for clinical AF using a smartphone photoplethysmography (PPG) application. Inclusion criteria are age ≥ 65 years and the ability to perform at least three PPG recordings within 6 months. Exclusion criteria are the presence of a cardiac implantable device, advanced dementia or a severe tremor. The PPG application records patients' pulse at their fingertip and determines the likelihood of clinical AF. If clinical AF is suspected after a positive PPG recording, a confirmatory electrocardiogram is performed. Patients undergo a comprehensive geriatric assessment and a frailty index is calculated. Risk scores for major bleeding (MB) are applied. Standard laboratory testing and additional laboratory analyses are performed to determine the ABC-bleeding risk score. Follow-up data will be collected at 6 months, 12 months and 3 years on the incidence of AF, MB, hospitalisation, stroke, progression of cognitive disorders and mortality. DISCUSSION: The Dutch-GERAF study will focus on frail older patients, who are underrepresented in randomised clinical trials. It will provide insight into the effectiveness of screening for clinical AF and the efficacy and safety of OAC in this high-risk population. TRIAL REGISTRATION: NCT05337202.

Time of onset of atrial fibrillation and atrial fibrillation progression data from the RACE V study.

AIMS: Atrial fibrillation (AF) progression is associated with adverse outcome, but the role of the circadian or diurnal pattern of AF onset remains unclear. We aim to assess the association between the time of onset of AF episodes with the clinical phenotype and AF progression in patients with self-terminating AF. METHODS AND RESULTS: The Reappraisal of AF: Interaction Between Hypercoagulability, Electrical Remodelling, and Vascular Destabilization in the Progression of AF study included patients with self-terminating AF who underwent extensive phenotyping at baseline and continuous rhythm monitoring with an implantable loop recorder (ILR). In this subanalysis, ILR data were used to assess the development of AF progression and the diurnal pattern of AF onset: predominant (>80%) nocturnal AF, predominant daytime AF, or mixed AF without a predominant diurnal AF pattern. The median follow-up was 2.2 (1.6-2.8) years. The median age was 66 (59-71) years, and 117 (42%) were women. Predominant nocturnal (n = 40) and daytime (n = 43) AF onset patients had less comorbidities compared to that of mixed (n = 195) AF patients (median 2 vs. 2 vs. 3, respectively, P = 0.012). Diabetes was more common in the mixed group (12% vs. 5% vs. 0%, respectively, P = 0.031), whilst obesity was more frequent in the nocturnal group (38% vs. 12% vs. 27%, respectively, P = 0.028). Progression rates in the nocturnal vs. daytime vs. mixed groups were 5% vs. 5% vs. 24%, respectively (P = 0.013 nocturnal vs. mixed and P = 0.008 daytime vs. mixed group, respectively). CONCLUSION: In self-terminating AF, patients with either predominant nocturnal or daytime onset of AF episodes had less associated comorbidities and less AF progression compared to that of patients with mixed onset of AF. CLINICAL TRIAL REGISTRATION: NCT02726698.

Long-term outcome of targeted therapy of underlying conditions in patients with early persistent atrial fibrillation and heart failure: data of the RACE 3 trial.

AIMS: The Routine vs. Aggressive risk factor driven upstream rhythm Control for prevention of Early persistent atrial fibrillation (AF) in heart failure (HF) (RACE 3) trial demonstrated that targeted therapy of underlying conditions improved sinus rhythm maintenance at 1 year. We now explored the effects of targeted therapy on the additional co-primary endpoints; sinus rhythm maintenance and cardiovascular outcome at 5 years. METHODS AND RESULTS: Patients with early persistent AF and mild-to-moderate stable HF were randomized to targeted or conventional therapy. Both groups received rhythm control therapy according to guidelines. The targeted group additionally received four therapies: angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (ARBs), statins, mineralocorticoid receptor antagonists (MRAs), and cardiac rehabilitation. The presence of sinus rhythm and cardiovascular morbidity and mortality at 5-year follow-up were assessed. Two hundred and sixteen patients consented for long-term follow-up, 107 were randomized to targeted and 109 to conventional therapy. At 5 years, MRAs [76 (74%) vs. 10 (9%) patients, P < 0.001] and statins [81 (79%) vs. 59 (55%), P < 0.001] were used more in the targeted than conventional group. Angiotensin-converting enzyme inhibitors/ARBs and physical activity were not different between groups. Sinus rhythm was present in 49 (46%) targeted vs. 43 (39%) conventional group patients at 5 years (odds ratio 1.297, lower limit of 95% confidence interval 0.756, P = 0.346). Cardiovascular mortality and morbidity occurred in 20 (19%) in the targeted and 15 (14%) conventional group patients, P = 0.353. CONCLUSION: In patients with early persistent AF and HF superiority of targeted therapy in sinus rhythm maintenance could not be preserved at 5-year follow-up. Cardiovascular outcome was not different between groups. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00877643.

Diagnostic yield and accuracy in a tertiary referral syncope unit validating the ESC guideline on syncope: a prospective cohort study.

AIMS: To assess in patients with transient loss of consciousness the diagnostic yield, accuracy, and safety of the structured approach as described in the ESC guidelines in a tertiary referral syncope unit. METHODS AND RESULTS: Prospective cohort study including 264 consecutive patients (≥18 years) referred with at least one self-reported episode of transient loss of consciousness and presenting to the syncope unit between October 2012 and February 2015. The study consisted of three phases: history taking (Phase 1), autonomic function tests (AFTs) (Phase 2), and after 1.5-year follow-up with assessment by a multidisciplinary committee (Phase 3). Diagnostic yield was assessed after Phases 1 and 2. Empirical diagnostic accuracy was measured for diagnoses according to the ESC guidelines after Phase 3. The diagnostic yield after Phase 1 (history taking) was 94.7% (95% CI: 91.1-97.0%, 250/264 patients) and increased to 97.0% (93.9-98.6%, 256/264 patients) after Phase 2. The overall diagnostic accuracy (as established in Phase 3) of the Phases 1 and 2 diagnoses was 90.6% (95% CI: 86.2-93.8%, 232/256 patients). No life-threatening conditions were missed. Three patients died, two unrelated to the cause of transient loss of consciousness, and one whom remained undiagnosed. CONCLUSION: A clinical work-up at a tertiary syncope unit using the ESC guidelines has a high diagnostic yield, accuracy, and safety. History taking (Phase 1) is the most important diagnostic tool. Autonomic function tests never changed the Phase 1 diagnosis but helped to increase the certainty of the Phase 1 diagnosis in many patients and yield additional diagnoses in patients who remained undiagnosed after Phase 1. Diagnoses were inaccurate in 9.4%, but no serious conditions were missed. This is adequate for clinical practice.

Temporal patterns and short-term progression of paroxysmal atrial fibrillation: data from RACE V.

AIMS: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression. METHODS AND RESULTS: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5-4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression. CONCLUSIONS: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier NCT02726698.

Origins of electronic band gap reduction in Cr/N codoped TiO2.

Recent studies indicated that noncompensated cation-anion codoping of wide-band-gap oxide semiconductors such as anatase TiO2 significantly reduces the optical band gap and thus strongly enhances the absorption of visible light [W. Zhu et al., Phys. Rev. Lett. 103, 226401 (2009)]. We used soft x-ray spectroscopy to fully determine the location and nature of the impurity levels responsible for the extraordinarily large (∼1 eV) band gap reduction of noncompensated codoped rutile TiO2. It is shown that Cr/N codoping strongly enhances the substitutional N content, compared to single element doping. The band gap reduction is due to the formation of Cr 3d3 levels in the lower half of the gap while the conduction band minimum is comprised of localized Cr 3d and delocalized N 2p states. Band gap reduction and carrier delocalization are critical elements for efficient light-to-current conversion in oxide semiconductors. These findings thus raise the prospect of using codoped oxide semiconductors with specifically engineered electronic properties in a variety of photovoltaic and photocatalytic applications.

[Coumarin or DOAC in frail elderly patients with atrial fibrillation?] / Cumarine of DOAC bij kwetsbare ouderen met atriumfibrilleren?

OBJECTIVE: To investigate whether frail elderly people with atrial fibrillation (AF) who are currently using a vitamin K antagonist (VKA) should be switched to a direct-acting oral anticoagulant (DOAC). DESIGN: Randomized clinical trial. METHODS: 662 frail elderly AF patients were switched to a DOAC, and 661 patients continued their VKA. The primary endpoint was a major or clinically relevant non-major bleeding during 1 year of follow-up. Secondary endpoints included thrombo-embolic events. RESULTS: The mean age of the included patients was 83 years. In the 'switch to DOAC arm', 101 bleeding events (15.3%) occurred and in the 'continue with VKA arm', 62 bleeding events (9.4%); an increase of 69% more bleeding events (P-value 0.001). The number of thrombo-embolic events was not significantly different between both groups. CONCLUSION: Switching from a VKA to a DOAC in frail elderly people with AF leads to 69% more bleeding, without a difference in thrombo-embolic events.

Direct Oral Anticoagulants in Older and Frail Patients with Atrial Fibrillation: A Decade of Experience.

INTRODUCTION: Both the prevalence of atrial fibrillation (AF) and its subsequent use of direct oral anticoagulants (DOACs) are rapidly increasing in patients of older age. In the absence of contra-indications, guidelines advocate anticoagulation based on the CHA2DS2-VASc score for all AF patients aged 75 and above. However, some practitioners are hesitant to prescribe anticoagulants to older and frail patients due to perceived elevated bleeding risks. This review delves into the comparative treatment outcomes of DOACs versus vitamin K antagonists (VKAs) in older patients with AF, particularly focusing on those of advanced age, frailty, increased risk of falling, chronic kidney disease (CKD), or with a history of major bleeding. Additionally, considerations on the use of off-label DOAC doses, the role of left atrial appendage (LAA) closure and future developments in factor XIa-inhibitors will be discussed. RESULTS: While strong evidence supports the use of DOACs in the vital older patients with nonvalvular AF, it remains scant in frail patient groups. There is some evidence from non-randomized studies suggesting that the effect of DOACs compared with VKAs is consistent between frail and nonfrail patients. However, recent findings from a single randomized trial showed increased bleeding risks but comparable thromboembolic outcomes in frail individuals switching from VKAs to DOACs. In patients with an increased risk of falling, data suggest no relevant interaction of increased risk of falling on the effectiveness and safety of DOACs compared with warfarin. Resuming oral anticoagulants in patients with Af after major bleeding seems to be beneficial. Off-label low-dose DOAC is often prescribed to patients who were underrepresented in larger randomized trails because of an elevated risk of bleeding or overexposure to DOACs, but its effect on clinical outcomes remains uncertain. CONCLUSIONS: DOACs are the recommended oral anticoagulant for vital older patients with AF. The scarcity of data backing DOAC use in frail individuals, those with renal impairments, or significant bleeding history underscores the necessity for further investigation. However, existing evidence suggests at least similar effectiveness and safety and potential benefits for DOACs in these patient subsets. Therefore, there is no reason to suggest these patients should be treated differently than the established guidelines regarding anticoagulation.

Labile assembly of a tardigrade protein induces biostasis.

Tardigrades are microscopic animals that survive desiccation by inducing biostasis. To survive drying tardigrades rely on intrinsically disordered CAHS proteins, which also function to prevent perturbations induced by drying in vitro and in heterologous systems. CAHS proteins have been shown to form gels both in vitro and in vivo, which has been speculated to be linked to their protective capacity. However, the sequence features and mechanisms underlying gel formation and the necessity of gelation for protection have not been demonstrated. Here we report a mechanism of fibrillization and gelation for CAHS D similar to that of intermediate filament assembly. We show that in vitro, gelation restricts molecular motion, immobilizing and protecting labile material from the harmful effects of drying. In vivo, we observe that CAHS D forms fibrillar networks during osmotic stress. Fibrillar networking of CAHS D improves survival of osmotically shocked cells. We observe two emergent properties associated with fibrillization; (i) prevention of cell volume change and (ii) reduction of metabolic activity during osmotic shock. We find that there is no significant correlation between maintenance of cell volume and survival, while there is a significant correlation between reduced metabolism and survival. Importantly, CAHS D's fibrillar network formation is reversible and metabolic rates return to control levels after CAHS fibers are resolved. This work provides insights into how tardigrades induce reversible biostasis through the self-assembly of labile CAHS gels.

Healthcare utilisation and quality of life according to atrial fibrillation burden, episode frequency and duration.

BACKGROUND: We aimed to evaluate the association between atrial fibrillation (AF) burden, duration and number of episodes with healthcare utilisation and quality of life in patients with early paroxysmal AF without a history of AF. METHODS: In this observational cohort study, we included 417 patients with paroxysmal AF from the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V) Study. Patients were monitored with an insertable cardiac monitor for 1 year. Outcomes collected were healthcare utilisation, and quality of life assessed using the Atrial Fibrillation Severity Scale and EuroQol EQ-5D-5L questionnaires. RESULTS: During 1 year of follow-up, 63 973 AF episodes were detected in 353 (85%) patients. The median AF burden was 0.7% (IQR 0.1-4.0%). AF ablation was performed more frequently in patients with intermediate-to-high AF burdens (>0.2%) (16.2% vs 5.9%, p=0.01) and longer AF episode duration (>1 hour) (15.8% vs 2.0%, p=0.01), whereas cardioversions were more frequent in patients with longer episode duration (>1 hour) (9.5% vs 0%, p=0.04) and intermediate (0.2-1.9%) (but not high) AF burdens (13.6% vs 4.2%, p=0.01). Patients with many episodes (>147) reported higher symptom severity (p=0.001). No differences in symptom severity nor in EQ-5D-5L scores according to AF burden or duration were observed. CONCLUSION: In patients with early paroxysmal AF, higher AF burden and longer episode duration were associated with increased rates of healthcare utilisation but not with symptoms and quality of life. Patients with a higher number of episodes experienced more severe symptoms. TRIAL REGISTRATION NUMBER: NCT02726698.

[Anticoagulation useful in short episodes of atrial fibrillation?] / Antistolling zinvol bij kortdurend atriumfibrilleren?

In patients with short episodes of clinical, non-triggered AF is the evidence for long-term anticoagulation based on the CHA2DS2-VASc score strong. In situations where a temporary trigger for AF is observed (e.g. after surgery or an infection), or when AF is only detected on a cardiac implantable electronic device (CIED) or smartwatch, the evidence for anticoagulation is less well established. Despite the short duration of the AF episode(s), both patients with subclinical or triggered AF are often at an inherently increased risk of stroke or thromboembolism. In some of these cases long-term anticoagulation can be considered, especially when other cardiovascular risk factors are present. Important considerations when deciding to start with long-term anticoagulation are the individually estimated risk of thrombosis and bleeding, the implementation of shared decision making, and the optimization of the overall cardiovascular risk management.

The Use of Oral Anticoagulation Is Not Independently Associated with Mortality in Frail Older Patients with Repeated Falls.

BACKGROUND: Particularly in frail patients, anticoagulation may be underused because of the fear of bleeding. OBJECTIVE: To determine whether the use of antithrombotic medication is an independent risk factor for mortality in frail elderly with repeated falls. METHODS: All patients aged 65 years or older at the Fall and Syncope Clinic were eligible. Frailty was calculated with a Frailty Index (FI) based on the accumulation of deficits model. Risks were calculated with a cox regression analysis, adjusted for age, sex, and Frailty Index. RESULTS: 663 patients were included in this analysis. The median age was 80 years, 438 were women (66%), 73% had polypharmacy, and 380 patients (57%) had cognitive impairment. The mean FI was 0.23 (sd 0.09), 182 patients were moderately frail (27.5%), and 259 (39.1%) were severely frail. A total of 140 (21%) used oral anticoagulation and 223 (34%) used antiplatelet agents. A total of 196 patients (29.6%) died during follow-up. In the adjusted cox regression model, the use of neither antiplatelets nor anticoagulation was associated with mortality. A strong association was found with frailty (HR 74.0, 95% CI 13.1-417.3) and a weak association with age (HR 1.05, 95% CI 1.03-1.08). A lower risk of mortality was seen in women (HR 0.5, 95% CI 0.3-0.6). CONCLUSIONS: In this cohort of frail older patients, there was no independent association between the use of antithrombotic medication and mortality. A strong association with mortality was found with frailty, a weak association was found with age, and a lower mortality risk was found in women. Our data indicate that the fear of bleeding or increased mortality in frail patients with an indication for oral anticoagulation may be unjustified.

Health economic evaluation of nation-wide screening programmes for atrial fibrillation in the Netherlands.

AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guidelines to prevent strokes. Cost-effectiveness analyses of different screening programmes for AF are difficult to compare because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programmes in the Netherlands. METHODS AND RESULTS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY, and ROCKET AF trials combined with Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed. The maximum number of newly detected AF patients in the Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of >3000 strokes prevented using single-time point AF screening. Compared with no screening, screening 100 000 people provided a gain in QALYs ranging from 984 to 8727 and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. The probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥75 years visiting the geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥65 years visiting the GPs office had the highest impact on strokes prevented. CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.

Atrial fibrillation in cancer: thromboembolism and bleeding in daily practice.

Background: Cancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF). Objectives: We aimed to describe current anticoagulant practice in patients with AF and active cancer, present incidences of thromboembolic and bleeding complications, and evaluate the association between cancer type or anticoagulant management strategy with AF-related complications. Methods: This retrospective study identified patients with AF and active cancer in 2 hospitals between January 1, 2012, and December 31, 2017. Follow-up lasted for 2 years. Data on cancer and anticoagulant treatment were collected. The outcomes of interest included ischemic stroke or transient ischemic attack (TIA) and clinically relevant nonmajor bleeding (CRNMB/MB). Incidence rates (IRs) per 100 patient-years and subdistribution hazard ratios (SHRs) with corresponding 95% Cis were estimated. Results: We identified 878 patients with AF who developed cancer (cohort 1) and 335 patients with cancer who developed AF (cohort 2). IRs for ischemic stroke/TIA and MB/CRNMB were 3.9 (2.8-5.3) and 15.7 (13.3-18.5) for cohort 1 and 4.0 (2.2-6.7) and 16.7 (12.6-21.7) for cohort 2. 14.2% (cohort 1) and 19.1% (cohort 2) of patients with a CHA2DS2-VASc score of ≥2 did not receive anticoagulant treatment. Withholding anticoagulants was associated with thromboembolic complications (SHR: 5.1 [3.20-8.0]). In nonanticoagulated patients with a CHA2DS2-VASc score of <2, IRs for stroke/TIA were 4.5 (0.75-15.0; cohort 1) and 16.0 (5.1-38.7; cohort 2). Conclusion: Patients with AF and active cancer experience high rates of thromboembolic and bleeding complications, underlying the complexity of anticoagulant management in these patients. Our data suggest that the presence of cancer is an important factor in determining the indication for anticoagulants in patients with a low CHA2DS2-VASc score.