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Background: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). Hypothesis: An externally validated model improves ICH risk stratification. Methods: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD‐AF (Global Anticoagulant Registry in the FIELD‐Atrial Fibrillation) and ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. Results: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2‐year period (0.31 per 100 person‐years; 95% confidence interval [CI]: 0.28–0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate‐to‐severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non‐VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25–2.08; p =.0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism‐corrected C‐statistic: 0.68; 95% CI: 0.65–0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. Conclusions: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication. [ABSTRACT FROM AUTHOR]

Aims: This study aims to describe both management and prognosis of patients with diabetes mellitus (DM) and newly diagnosed atrial fibrillation (AF), overall as well as by antidiabetic treatment, and to assess the influence of oral anticoagulation (OAC) on outcomes by DM status. Methods: The study population comprised 52 010 newly diagnosed patients with AF, 11 542 DM and 40 468 non‐DM, enrolled in the GARFIELD‐AF registry. Follow‐up was truncated at 2 years after enrolment. Comparative effectiveness of OAC versus no OAC was assessed by DM status using a propensity score overlap weighting scheme and weights were applied to Cox models. Results: Patients with DM [39.3% oral antidiabetic drug (OAD), 13.4% insulin ± OAD, 47.2% on no antidiabetic drug] had higher risk profile, OAC use, and rates of clinical outcomes compared with patients without DM. OAC use was associated in patients without DM and patients with DM with lower risk of all‐cause mortality [hazard ratio 0.75 (0.69‐0.83), 0.74 (0.64‐0.86), respectively] and stroke/systemic embolism (SE) [0.69 (0.58‐0.83), 0.70 (0.53‐0.93), respectively]. The risk of major bleeding with OAC was similarly increased in patients without DM and those with DM [1.40 (1.14‐1.71), 1.37 (0.99‐1.89), respectively]. Patients with insulin‐requiring DM had a higher risk of all‐cause mortality and stroke/SE [1.91 (1.63‐2.24)], [1.57 (1.06‐2.35), respectively] compared with patients without DM, and experienced significant risk reductions of all‐cause mortality and stroke/SE with OAC [0.73 (0.53‐0.99); 0.50 (0.26‐0.97), respectively]. Conclusions: In both patients with DM and patients without DM with AF, OAC was associated with lower risk of all‐cause mortality and stroke/SE. Patients with insulin‐requiring DM derived significant benefit from OAC. [ABSTRACT FROM AUTHOR]

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is a worldwide non-interventional study of stroke prevention in patients with non-valvular AF. Methods and results: 52,080 patients with newly diagnosed AF were prospectively enrolled from 2010 to 2016. 4121 (7.9%) of these patients were recruited in DACH [Germany (n = 3567), Austria (n = 465) and Switzerland (n = 89) combined], and 47,959 patients were from 32 countries in other regions worldwide (ORW). Hypertension was most prevalent in DACH and ORW (85.3% and 75.6%, respectively). Diabetes, hypercholesterolaemia, carotid occlusive disease and vascular disease were more prevalent in DACH patients vs ORW (27.6%, 49.4%, 5.8% and 29.0% vs 21.7%, 40.9%, 2.8% and 24.5%). The use of non-vitamin K antagonist oral anticoagulants (NOACs) increased more in DACH over time. Management of vitamin K antagonists was suboptimal in DACH and ORW (time in therapeutic range of INR ≥ 65% in 44.6% and 44.4% of patients or ≥ 70% in 36.9% and 36.0% of patients, respectively). Adjusted rates of cardiovascular mortality and MI/ACS were higher in DACH while non-haemorrhagic stroke/systemic embolism was lower after 2-year follow-up. Conclusions: Similarities and dissimilarities in AF management and clinical outcomes are seen in DACH and ORW. The increased use of NOAC was associated with a mismatch of risk-adapted anticoagulation (over-and-undertreatment) in DACH. Suboptimal control of INR requires educational activities in both regional groups. Higher rates of cardiovascular death in DACH may reflect the higher risk profile of these patients and lower rates of non-haemorrhagic stroke could be associated with increased NOAC use. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to identify relationships in recently diagnosed atrial fibrillation (AF) patients with respect to anticoagulation status, use of guideline-directed medical therapy (GDMT) for comorbid cardiovascular conditions (co-GDMT), and clinical outcomes. The Global Anticoagulant Registry in the FIELD (GARFIELD)-AF is a prospective, international registry of patients with recently diagnosed non-valvular AF at risk of stroke (NCT01090362). Methods and results: Guideline-directed medical therapy was defined according to the European Society of Cardiology guidelines. This study explored co-GDMT use in patients enrolled in GARFIELD-AF (March 2013–August 2016) with CHA2DS2-VASc ≥ 2 (excluding sex) and ≥1 of five comorbidities—coronary artery disease, diabetes mellitus, heart failure, hypertension, and peripheral vascular disease (n = 23 165). Association between co-GDMT and outcome events was evaluated with Cox proportional hazards models, with stratification by all possible combinations of the five comorbidities. Most patients (73.8%) received oral anticoagulants (OACs) as recommended; 15.0% received no recommended co-GDMT, 40.4% received some, and 44.5% received all co-GDMT. At 2 years, comprehensive co-GDMT was associated with a lower risk of all-cause mortality [hazard ratio (HR) 0.89 (0.81–0.99)] and non-cardiovascular mortality [HR 0.85 (0.73–0.99)] compared with inadequate/no GDMT, but cardiovascular mortality was not significantly reduced. Treatment with OACs was beneficial for all-cause mortality and non-cardiovascular mortality, irrespective of co-GDMT use; only in patients receiving all co-GDMT was OAC associated with a lower risk of non-haemorrhagic stroke/systemic embolism. Conclusion: In this large prospective, international registry on AF, comprehensive co-GDMT was associated with a lower risk of mortality in patients with AF and CHA2DS2-VASc ≥ 2 (excluding sex); OAC therapy was associated with reduced all-cause mortality and non-cardiovascular mortality, irrespective of co-GDMT use. Clinical Trial Registration: Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362. Graphical abstract [ABSTRACT FROM AUTHOR]

Aims Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation. Methods and results Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48–0.71 (recurrence) and 0.61–0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% –19% for bleeding. Conclusion The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making. [ABSTRACT FROM AUTHOR]

Background: Differences in the clinical outcomes and level of risk among Asian versus non-Asian patients with atrial fibrillation (AF) have been sparsely investigated., Objective: To provide a contemporary prospective comparison of outcomes for newly diagnosed patients with AF, between Asian and non-Asian regions., Methods: Six Asian countries (China, Japan, India, Singapore, South Korea and Thailand) and 29 countries outside Asia participated in the Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) study. Newly diagnosed patients with AF, enrolled between 2010 and 2016, were followed up for≥2 years. The outcome studies were all-cause, cardiovascular and non-cardiovascular mortality, non-haemorrhagic stroke/systemic embolism (SE), major bleeding. The association of geographical region with clinical outcomes (event rates per 100 person-years) were estimated using multivariable Cox models., Results: 13 841/52 057 (26.6%) GARFIELD-AF participants were enrolled in Asia. Average age and prevalence of cardiovascular comorbidities were lower than in non-Asian countries and patients at high risk of stroke (ie, CHA 2 DS 2 -VASc≥2 excl. sex) were less frequently anticoagulated (60.1% vs 73.2%). Non-vitamin K oral anticoagulant (NOAC) was similar in both regions (∼28%), though Asian patients were more frequently underdosed. Both Asian and non-Asian patients who received NOAC at enrolment experienced lower all-cause mortality and non-haemorrhagic stroke/SE compared with patients on other treatments or none.All-cause mortality, non-cardiovascular mortality and major bleeding were less frequent in patients from Asia versus non-Asia (HR (95% CI): 0.62 (0.39 to 0.99), 0.52 (0.28 to 0.97), 0.58 (0.36 to 0.96), respectively). Associations of moderate-to-severe chronic kidney disease and vascular disease with increased risk of all-cause mortality were stronger in Asian versus non-Asian patients (interaction p values: 0.0250 and 0.0076, respectively). There was notable heterogeneity in oral anticoagulant (OAC) usage within the Asian countries., Conclusions: Patients in Asian countries had a lower risk of all-cause mortality and major bleeding compared to the rest of the world. NOAC had evident benefits for reducing mortality and stroke across populations. Further studies on sociocultural impacts on OAC outcomes are needed., Trial Registration Number: ClinicalTrials.gov NCT01090362., Competing Interests: Competing interests: JC has received institutional grants and personal fees from Anthos, Bayer, BMS/Pfizer and Daichi Sankyo. KS has consultancy with Johnson & Johnson, Element Science, Artivion, Novartis; AKK has received grants and personal fees from Bayer AG, Sanofi and Anthos Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Aims: This study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry., Methods and Results: Patients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models. Among GARFIELD-AF patients on apixaban, 2570/3615 (71%) would have been eligible for ARISTOTLE. Among patients using rivaroxaban, 2005/4914 (41%) would have been eligible for ROCKET AF. Eligibility rates were steady over time, with minor differences across medical specialties. Real-world AF patients selected according to trial criteria had lower cardiovascular burden than the original trial participants, especially compared with ROCKET AF. HRs (95% CI) for apixaban versus VKA among ARISTOTLE-eligible users were 0.57 (0.34 to 0.94) for stroke/systemic embolism, 0.76 (0.48 to 1.20) for major bleeding and 0.89 (0.70 to 1.12) for all-cause mortality. Among ROCKET AF-eligible rivaroxaban users, HRs for rivaroxaban versus VKA were 0.90 (0.57 to 1.43), 0.92 (0.59 to 1.43) and 0.86 (0.69 to 1.08), respectively. All safety and efficacy estimates were similar to those in the original trials., Conclusion: Real-world representativeness of the selection criteria was greater for ARISTOTLE than ROCKET AF. The pivotal randomised trials of apixaban and rivaroxaban versus warfarin can be successfully emulated in real-world AF patients by applying trial-specific selection criteria and appropriate methodology for non-randomised treatment allocation., Trial Registration Number: NCT01090362., Competing Interests: Competing interests: JC reports institutional grants and personal fees from Bayer, Boehringer Ingelheim, Pfizer/BMS and Daiichi Sankyo. KP has consultancies with Johnson & Johnson, Element Science, Artivion and Novartis. FV received grants from Bayer Healthcare and personal fees from Bayer Healthcare, BMS/Pfizer, Daiichi-Sankyo, and Boehringer-Ingelheim. J-PB received a personal fee from Thrombosis Research Institute, during the conduct of the study. FM is a former employee of Bayer AG. FC reports speaker fees from Boehringer Ingelheim Pharma, Bayer, Pfizer and Daiichi-Sankyo Europe and a modest research grant from Daiichi-Sankyo Europe. HG received honoraria from Bayer Australia, Eli Lilly Australia, Pfizer Australia and BMS Australia. AKK received personal fees and grants from Bayer AG, Sanofi S.A. and Anthos Therapeutics. JCLH, SV, REH and ACPB report no conflicts of interest., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Investigate real-world outcomes of early rhythm versus rate control in patients with recent onset atrial fibrillation., Methods: The Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) is an international multi-centre, non-interventional prospective registry of newly diagnosed (≤6 weeks' duration) atrial fibrillation patients at risk for stroke. Patients were stratified according to treatment initiated at baseline (≤48 days post enrolment), and outcome risks evaluated by overlap propensity weighted Cox proportional-hazards models., Results: Of 45,382 non-permanent atrial fibrillation patients, 23,858 (52.6 %) received rhythm control and 21,524 (47.4 %) rate control. Rhythm-controlled patients had lower median age (68.0 [Q1;Q3: 60.0;76.0] versus 73.0 [65.0;79.0]), fewer histories of stroke/transient ischemic attack/systemic embolism (9.4 % versus 13.0 %), and lower expected probabilities of death (median GARFIELD-AF death score 4.0 [2.3;7.5] versus 5.1 [2.8;9.2]). The two groups had the same median CHA 2 DS 2 -VASc scores (3.0 [2.0;4.0]) and similar proportions of anticoagulated patients (rhythm control: 66.0 %, rate control: 65.5 %). The propensity-score-weighted hazard ratios of rhythm vs rate control (reference) were 0.85 (95 % CI: 0.79-0.92, p-value < 0.0001) for all-cause mortality, 0.84 (0.72-0.97, p-value 0.020) for non-haemorrhagic stroke/systemic embolism and 0.90 (0.78-1.04, p-value 0.164) for major bleeding., Conclusion: Rhythm control strategy was initiated in about half of the patients with newly diagnosed non-valvular non-permanent atrial fibrillation. After balancing confounders, significantly lower risks of all-cause mortality and non-haemorrhagic stroke were observed in patients who received early rhythm control., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The authors declare the following potential conflicts of interest: MPK is a recipient of a grant to the institution from Bayer, for support of her ASTORIA study (unrelated to the current publication). TSH reports personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Imedic, Novartis, MSD, Sanofi, and Pfizer. DA reports personal fees from Bayer, Boehringer-Ingelheim, Bristol Meier Squibb, MSD and Pfizer, and grants to the institution from Medtronic and BMS. PJ has served as a consultant or on an advisory board for Bayer, Boehringer Ingelheim, and Novartis. AJC has received institutional grant funding and personal fees from Bayer, Boehringer Ingelheim, Bristol Meier Squibb, Daiichi Sankyo, and Pfizer, and personal fees from Sanofi, Menarini, Abbot, Boston Scientific and Medtronic. AKK has received grants and personal fees from Bayer AG, and Sanofi S.A., and Anthos Therapeutics. SH has received personal fees from Bayer, BMS, Daiichi Sankyo, Pfizer, and Sanofi. SG was a recipient of quality personal fees from Jansen and Antos, and Phillips, fees from the American Heart Association as an Associate Editor for Circulation, and Steering Committee fees from Duke University. EP declares honoraria for participation in clinical trials by Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, AstraZeneca, Daiichi Sankyo Pharma Development, GlaxoSmithKline DMPK. She received fees for contributions to advisory boards or oral presentations from Sanofi, Bayer, Lilly, AstraZeneca, Boehringer Ingelheim, Bayer, Pfizer, Bristol-Myers Squibb, Servier, Takeda-NYCOMED, GlaxoSmithKline, MEDICINES, Aspen, and Stada. PA reports research grants to the institution from Novo Nordisk, Sanofi, and Spark Therapeutics. All other authors have reported that they have no relationships relevant to the content of this paper to disclose.]., (© 2023 The Author(s).)

Aims: Deciding to stop or continue anticoagulation for venous thromboembolism (VTE) after initial treatment is challenging, as individual risks of recurrence and bleeding are heterogeneous. The present study aimed to develop and externally validate models for predicting 5-year risks of recurrence and bleeding in patients with VTE without cancer who completed at least 3 months of initial treatment, which can be used to estimate individual absolute benefits and harms of extended anticoagulation., Methods and Results: Competing risk-adjusted models were derived to predict recurrent VTE and clinically relevant bleeding (non-major and major) using 14 readily available patient characteristics. The models were derived from combined individual patient data from the Bleeding Risk Study, Hokusai-VTE, PREFER-VTE, RE-MEDY, and RE-SONATE (n = 15,141, 220 recurrences, 189 bleeding events). External validity was assessed in the Danish VTE cohort, EINSTEIN-CHOICE, GARFIELD-VTE, MEGA, and Tromsø studies (n = 59 257, 2283 recurrences, 3335 bleeding events). Absolute treatment effects were estimated by combining the models with hazard ratios from trials and meta-analyses. External validation in different settings showed agreement between predicted and observed risks up to 5 years, with C-statistics ranging from 0.48-0.71 (recurrence) and 0.61-0.68 (bleeding). In the Danish VTE cohort, 5-year risks ranged from 4% to 19% for recurrent VTE and 1% -19% for bleeding., Conclusion: The VTE-PREDICT risk score can be applied to estimate the effect of extended anticoagulant treatment for individual patients with VTE and to support shared decision-making., Competing Interests: Conflict of Interest: Marc Carrier reports research funding from BMS, Leo Pharma, and Pfizer, and honoraria from Bayer, Sanofi, BMS, Leo Pharma, Servier and Pfizer. All fees are paid to his institution. Ander Cohen reports grants or contracts, consulting fees and payment or honoraria from Bayer AG, Daiichi Sankyo, BMS/Pfizer, and AstraZeneca. All fees were paid to his company. Alfredo Farjat was a full-time employee at Thrombosis Research Institute when he collaborated with this study. Akos Ference Pap is an employee of Bayer AG. Samuel Goldhaber reports grants or contracts from Bayer, Boston Scientific BTG EKOS, NHLBI, BMS, Janssen and Pfizer, consulting fees from Agile, Pfizer, Bayer, speaker fees from Lankenau Grand Rounds in Medicine, Bakken Symposium -University of Minnesota, The Brigham Board Review in Critical Care ‘Virtual Studio/Distance Learning’, New York Cardiovascular Symposium, Latin American Anticoagulation Series Conference, Jeresaty Symposium—Trinity Health of New England, Rutgers New Jersey Medical School Grand Rounds, SBACV Symposium—Brazil Society of Angiology and Vascular Medicine, Brigham-Sheba Collaboration on Thrombosis and Vascular Medicine and Philippine Society of Vascular Medicine Annual Convention. Michael Grosso is an employee of Daiichi Sankyo. Ajay Kakkar reports grants from Bayer AG, Sanofi SA, personal fees from Anthos Therapeutics, Bayer AG, Sanofi S.A. Karen Pieper reports consulting fees from Cryolife, J&J Pharmaceuticals, Artivion and Element Science. Gary Raskob reports consultancy fees or honoraria from AMAG Pharma, Anylam, Anthos Therapeutics, Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb, Daiichi Sankyo Inc., Janssen Global Services LLC, Pfizer, and XaTrek; honoraria from BMS, Pfizer, Daiichi Sankyo; DSMB or advisory board membership from Anthos Therapetuics, Janssen, Bristol-Myers Squibb and Pfizer, leadership or fiduciary role in other board, society, committee or advocacy group of OU Health, stock or stock option ownership for AbbVie, Inc., Gilead Sciences Inc, GlaxoSmithKline, LLC., LLY, MRK, and Pfizer. Sam Schulman reports research grants, paid to his institution, from Octopharma, and consulting fees from Alexion, Bayer, Boehringer–Ingelheim, Sanofi, Daiichi Sankyo and Octopharma. Minggao Shi is an employee of Daiichi Sankyo. Phillip Wells reports grants and speaker fees from BMS/Pfizer, consulting fees from Anthos and speaker fees and consulting fees from Bayer Healthcare. All fees are paid to his institution. The other authors have nothing to declare., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The management of atrial fibrillation (AF), the most common sustained arrhythmia, impacts healthcare resource utilization (HCRU). This study aims to estimate global resource use in AF patients, using the GARFIELD-AF registry. A prospective cohort study was conducted to characterize HCRU in AF patients enrolled in sequential cohorts from 2012 to 2016 in 35 countries. Components of HCRU studied were hospital admissions, outpatient care visits, and diagnostic and interventional procedures occurring during follow-up. AF-related HCRU was reported as the percentage of patients demonstrating at least one event and was quantified as rate-per-patient-per-year (PPPY) over time. A total of 49,574 patients was analyzed, having an overall median follow-up of 719 days. Almost all patients (99.5%) had at least one outpatient care visit, while hospital admissions were the second most frequent medical contact, with similar proportions in North America (37.5%) and Europe (37.2%), and slightly higher in the other GARFIELD-AF countries (42.0%; namely Australia, Egypt, and South Africa). Asia and Latin America showed lower percentages of hospitalizations, outpatient care visits, and diagnostic and interventional procedures. Analyses of GARFIELD-AF highlighted the vast AF-related HCRU, underlying significant geographical differences in the type, quantity, and frequency of AF-related HCRU. These differences were likely attributable to health service availability and differing models of care.

Aims: To determine whether the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) integrated risk tool predicts mortality, non-haemorrhagic stroke/systemic embolism, and major bleeding for up to 2 years after new-onset AF and to assess how this risk tool performs compared with CHA2DS2-VASc and HAS-BLED., Methods and Results: Potential predictors of events included demographic and clinical characteristics, choice of treatment, and lifestyle factors. A Cox proportional hazards model was identified for each outcome by least absolute shrinkage and selection operator methods. Indices were evaluated in comparison with CHA2DS2-VASc and HAS-BLED risk predictors. Models were validated internally and externally in ORBIT-AF and Danish nationwide registries. Among the 52 080 patients enrolled in GARFIELD-AF, 52 032 had follow-up data. The GARFIELD-AF risk tool outperformed CHA2DS2-VASc for all-cause mortality in all cohorts. The GARFIELD-AF risk score was superior to CHA2DS2-VASc for non-haemorrhagic stroke, and it outperformed HAS-BLED for major bleeding in internal validation and in the Danish AF cohort. In very low- to low-risk patients [CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)], the GARFIELD-AF risk score offered strong discriminatory value for all the endpoints when compared to CHA2DS2-VASc and HAS-BLED. The GARFIELD-AF tool also included the effect of oral anticoagulation (OAC) therapy, thus allowing clinicians to compare the expected outcome of different anticoagulant treatment decisions [i.e. no OAC, non-vitamin K antagonist (VKA) oral anticoagulants, or VKAs]., Conclusions: The GARFIELD-AF risk tool outperformed CHA2DS2-VASc at predicting death and non-haemorrhagic stroke, and it outperformed HAS-BLED for major bleeding in overall as well as in very low- to low-risk group patients with AF., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF: NCT01090362, ORBIT-AF I: NCT01165710; ORBIT-AF II: NCT01701817., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)