AIMS:We examined the predictive value of soluble levels of triggering receptor expressed on myeloid cells 1 (sTREM-1) for incident cardiovascular disease (CVD). METHODS:The main analysis was conducted in an observational prospective cohort. Adjudicated CVD events included coronary heart disease, stroke, heart failure and peripheral artery disease. sTREM-1 measures were centralized using a protocol optimized for Meso Scale Discovery technology. RESULTS:Among 9097 CVD-free participants (39% females, mean age 59.6±6.3 years), median sTREM-1 concentration was 193.41 pg/mL (IQR= 158.13 to 241.54) at baseline (2008 to 2012). Over 10.1 years of median follow-up (IQR= 9.2 to 12.0), 444 participants experienced 479 CVD events. Higher sTREM-1 concentrations were associated with higher risk of CVD in multivariable Cox proportional hazard model (HR 200-290 vs. <200pg/ml= 4.25;95% CI:3.20 to 5.63 and HR >290 vs. <200pg/ml=10.40;95% CI:7.72 to 14.02). Results were consistent across CVD subtypes. Adding sTREM-1 to SCORE2-SCORE2 OP improved the Harell-C index (C-index 0.79 vs. 0.71; bootstrapped C index difference: 0.084; 95% CI: 0.083 to 0.085) overall including among individuals at low to moderate 10-year risk of CHD or stroke, and reclassification: categorical NRI: 0.34; 95% CI: 0.28 to 0.40. Findings were similar with other recommended risk scores. CONCLUSIONS:In this prospective study, higher circulating sTREM-1 levels were independently associated with incident CVD. Addition of sTREM-1 to established risk scores was associated with improvements in discrimination and reclassification metrics, supporting its potential relevance as a candidate biomarker for further evaluation in primary prevention.

BackgroundCurrent classification of Acute Myocardial Infarction (AMI) into ST-elevation (STEMI) and non-ST-elevation (NSTEMI) myocardial infarction does not fully reflect the clinical heterogeneity of patients.ObjectivesTo identify clinically meaningful phenotypes of AMI patients using an unsupervised clustering approach and assess their associations with management strategies and long-term outcomes.MethodsHierarchical agglomerative clustering using Ward’s method was performed in 4,947 patients from the French FAST-MI 2015 nationwide registry. Clustering was based on baseline clinical, demographic, and laboratory features. Between-cluster differences in baseline characteristics, management, in-hospital complications, and 1-year mortality were analyzed.ResultsFour phenotypic clusters were identified. Cluster 1 (n = 1,488) gathered older patients, predominantly men, with typical coronary risk factors, intermediate risk profile, and balanced STEMI/NSTEMI presentations. Cluster 2 (n = 1,305) gathered older polymorbid patients, 45% were women, 60% with NSTEMI presentation, with limited use of invasive strategies (71%), and a high 1-year mortality. Cluster 3 (n = 815) gathered young (mean age 44 years), predominantly male patients, with a high prevalence of smoking (73%) and few comorbidities, 62% STEMI, high rates of revascularization, and excellent prognosis. Cluster 4 (n = 1,339) was close to Cluster 3 with a more metabolic profile with higher rates of obesity, diabetes, and dyslipidemia, also with favorable outcomes. In-hospital complications were more frequent in Clusters 1 and 2. One-year mortality was lowest in Clusters 3 and 4 (1.5 and 2.3%), intermediate in Cluster 1 (6.0%), and highest in Cluster 2 (15.7%).ConclusionUnsupervised clustering identified four clinically relevant AMI phenotypes with distinct characteristics, management patterns, and prognoses. This data-driven classification highlights the diversity of AMI presentations and may offer complementary insights for patient profiling and risk stratification.

Importance:Anterior acute myocardial infarction is associated with increased risk of left ventricular (LV) thrombus. The benefit and risk of adding an oral anticoagulant to dual antiplatelet therapy (DAPT) in preventing LV thrombus remain uncertain. Objective:To determine whether the addition of low-dose rivaroxaban to DAPT reduces the incidence of LV thrombus at 1 month in patients with anterior ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants:This multicenter, open-label, blinded-end point randomized clinical trial was performed in 29 centers in France. The trial was nested in the ongoing FRENCHIE (French Cohort of Myocardial Infarction Evaluation) registry. Between October 2021 and January 2023, patients with anterior STEMI were enrolled. The last date of participant follow-up was in March 2023. Data analysis was performed from September 2024 to July 2025. Interventions:Patients were randomized to receive either DAPT plus rivaroxaban, 2.5 mg, twice daily for 4 weeks (n = 283) or DAPT alone (aspirin ≤100 mg per day and either clopidogrel, 75 mg per day, or ticagrelor, 90 mg twice a day [n = 277]), as soon as possible following completion of the initial percutaneous coronary intervention or angiography procedure. Main Outcomes and Measures:The primary end point was presence of LV thrombus on contrast-enhanced cardiac magnetic resonance imaging at 1 month. Results:Among 560 patients with anterior STEMI enrolled (mean [SD] age, 61.1 [11.6] years; 121 female patients [21.6%]), LV thrombus was detected in 38 patients (13.7%) receiving rivaroxaban and 47 patients (16.6%) with DAPT alone (difference, -2.9%; 95% CI, -8.9% to 3.2%; P = .34). No difference was observed between the 2 groups regarding the largest diameter of LV thrombus or the incidence of major adverse cardiovascular events. The incidence of major bleeding events (Bleeding Academic Research Consortium [BARC] ≥type 2) was also comparable (4 [1.5%] with DAPT plus rivaroxaban vs 2 [0.7%] with DAPT alone; difference, 0.7%; 95% CI, -1.3% to 3.1%), whereas minor bleeding events (BARC type 1) occurred more frequently in the DAPT plus rivaroxaban group (45 [16.4%] vs 20 [7.2%]; difference, 9.3%; 95% CI, 3.6%-14.8%). Conclusions and Relevance:In this multicenter randomized clinical trial among patients with anterior STEMI, the addition of low-dose rivaroxaban to DAPT did not demonstrate a statistically significant reduction in LV thrombus formation at 1 month but did increase minor bleeding. Given the limited power of the study, these findings should be interpreted with caution, as a modest effect cannot be excluded. Trial Registration:ClinicalTrials.gov Identifier: NCT05077683.

BACKGROUND:Coronary revascularization is a key treatment for coronary artery disease (CAD). Over the past 15years, several randomized trials have shown that it failed to improve life expectancy in most patients with stable CAD. AIM:To compare trends in the use of coronary revascularization from 2012 to 2018 in France and the United States (US). METHODS:Administrative databases were used in both countries to identify patients ≥35years of age, hospitalized for CAD or congestive heart failure (CHF) undergoing coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), as identified from the International Classification of Diseases coding system. Independent correlates of the use of coronary revascularization were also investigated. RESULTS:In France, from 2012 to 2018, coronary revascularization increased by 13.3% among patients aged 35-64years and by 24.6% among those aged ≥65years. In contrast, in the US, it decreased by 16.3% and 19.6%, respectively. These trends were mainly related to the use of PCI: +15.8% and +28.8% in France versus-17.6% and-20.4% in the US. These divergent trends could not be explained solely by changes in the number of hospitalizations for CAD/CHF. In both countries and for both periods, use of revascularization was independently related to age, number of medical diagnoses, sex and income. CONCLUSION:Divergent trends in the use of coronary revascularization were observed in France and the US that could not be explained by trends in the number of CAD/CHF hospitalizations, nor by differences in the correlates of its use.

QuestionDoes adding low-dose rivaroxaban to dual antiplatelet therapy (DAPT) reduce left ventricular (LV) thrombus formation in patients with anterior acute myocardial infarction?FindingsIn this randomized clinical trial of 560 patients with anterior ST-segment elevation myocardial infarction (STEMI), adding low-dose rivaroxaban to DAPT did not significantly reduce LV thrombus formation at 1 month but did increase minor bleeding.MeaningIn this study, in patients with anterior STEMI, the addition of low-dose rivaroxaban to DAPT did not demonstrate a statistically significant reduction in LV thrombus formation at 1 month but increased minor bleeding; given the limited power of the study, these findings should be interpreted with caution. ImportanceAnterior acute myocardial infarction is associated with increased risk of left ventricular (LV) thrombus. The benefit and risk of adding an oral anticoagulant to dual antiplatelet therapy (DAPT) in preventing LV thrombus remain uncertain.ObjectiveTo determine whether the addition of low-dose rivaroxaban to DAPT reduces the incidence of LV thrombus at 1 month in patients with anterior ST-segment elevation myocardial infarction (STEMI).Design, Setting, and ParticipantsThis multicenter, open-label, blinded-end point randomized clinical trial was performed in 29 centers in France. The trial was nested in the ongoing FRENCHIE (French Cohort of Myocardial Infarction Evaluation) registry. Between October 2021 and January 2023, patients with anterior STEMI were enrolled. The last date of participant follow-up was in March 2023. Data analysis was performed from September 2024 to July 2025.InterventionsPatients were randomized to receive either DAPT plus rivaroxaban, 2.5 mg, twice daily for 4 weeks (n = 283) or DAPT alone (aspirin <= 100 mg per day and either clopidogrel, 75 mg per day, or ticagrelor, 90 mg twice a day [n = 277]), as soon as possible following completion of the initial percutaneous coronary intervention or angiography procedure.Main Outcomes and MeasuresThe primary end point was presence of LV thrombus on contrast-enhanced cardiac magnetic resonance imaging at 1 month.ResultsAmong 560 patients with anterior STEMI enrolled (mean [SD] age, 61.1 [11.6] years; 121 female patients [21.6%]), LV thrombus was detected in 38 patients (13.7%) receiving rivaroxaban and 47 patients (16.6%) with DAPT alone (difference, -2.9%; 95% CI, -8.9% to 3.2%; P = .34). No difference was observed between the 2 groups regarding the largest diameter of LV thrombus or the incidence of major adverse cardiovascular events. The incidence of major bleeding events (Bleeding Academic Research Consortium [BARC] >= type 2) was also comparable (4 [1.5%] with DAPT plus rivaroxaban vs 2 [0.7%] with DAPT alone; difference, 0.7%; 95% CI, -1.3% to 3.1%), whereas minor bleeding events (BARC type 1) occurred more frequently in the DAPT plus rivaroxaban group (45 [16.4%] vs 20 [7.2%]; difference, 9.3%; 95% CI, 3.6%-14.8%).Conclusions and RelevanceIn this multicenter randomized clinical trial among patients with anterior STEMI, the addition of low-dose rivaroxaban to DAPT did not demonstrate a statistically significant reduction in LV thrombus formation at 1 month but did increase minor bleeding. Given the limited power of the study, these findings should be interpreted with caution, as a modest effect cannot be excluded.Trial RegistrationClinicalTrials.gov Identifier: NCT05077683 This multicenter randomized clinical trial conducted in France determines whether the addition of low-dose rivaroxaban to dual antiplatelet therapy reduces the incidence of left ventricular thrombus at 1 month in patients with anterior ST-segment elevation myocardial infarction.

Antiplatelet therapy with low-dose aspirin, alone or as dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor, is used in secondary prevention following myocardial infarction (MI). However, the optimal duration of DAPT is unknown. This cohort study performed in the French nationwide claims database compared 3-year outcomes between DAPT and low-dose aspirin alone pursued beyond 1 year after MI. All adults discharged from hospital following MI in 2013–2014, and who survived ≥ 1 year under DAPT, without rehospitalization for acute coronary syndrome or major bleeding were enrolled (N = 51,468). The primary outcome was a composite of MI, stroke, major bleeding, or all-cause death during the 3 years following the index date (defined as 365 days after MI). Secondary outcomes were a composite of MI, stroke, and all-cause death, and each component of the primary composite. DAPT and low-dose aspirin exposure periods were analyzed as time-dependent variables and compared using hazard ratios (HR) from Cox proportional hazard or Fine–Gray competing risks models, adjusted using a high-dimensional disease risk score. The 3-year cumulative follow-up duration was 93,398 person-years (DAPT exposure: 26,223 person-years; low-dose aspirin exposure: 67,175 person-years). HRs for DAPT versus low-dose aspirin were 0.93 (0.85–1.03) for the primary composite outcome, 0.93 (0.84–1.03) for the secondary composite outcome, 1.04 (0.87–1.25) for MI, 0.91 (0.70–1.17) for stroke, 1.19 (0.88–1.60) for major bleeding, and 0.94 (0.83–1.07) for death. This national cohort study did not find a significant benefit of continued DAPT beyond 1 year after MI compared with low-dose aspirin. This study was registered with the European Medicines Agency EUPASS registry ( https://catalogues.ema.europa.eu/catalogue-rwd-studies ; registration no. EUPAS29177).

BACKGROUND:The appropriate antithrombotic regimen for patients with chronic coronary syndrome who are at high atherothrombotic risk and receiving long-term oral anticoagulation remains unknown. METHODS:We conducted a multicenter, double-blind, randomized, placebo-controlled trial in France involving patients with chronic coronary syndrome who had undergone a previous stent implantation (>6 months before enrollment) and were at high atherothrombotic risk and currently receiving long-term oral anticoagulation. The patients were randomly assigned in a 1:1 ratio to receive aspirin (100 mg once daily) or placebo; all the patients continued to receive their current oral anticoagulation therapy. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia. The key safety outcome was major bleeding. RESULTS:A total of 872 patients underwent randomization; 433 were assigned to the aspirin group, and 439 to the placebo group. The trial was stopped early at the advice of the independent data and safety monitoring board after a median follow-up of 2.2 years because of an excess of deaths from any cause in the aspirin group. A primary efficacy outcome event occurred in 73 patients (16.9%) in the aspirin group and in 53 patients (12.1%) in the placebo group (adjusted hazard ratio, 1.53; 95% confidence interval [CI], 1.07 to 2.18; P = 0.02). Death from any cause occurred in 58 patients (13.4%) in the aspirin group and in 37 (8.4%) in the placebo group (adjusted hazard ratio, 1.72; 95% CI, 1.14 to 2.58; P = 0.01). Major bleeding occurred in 44 patients (10.2%) in the aspirin group and in 15 patients (3.4%) in the placebo group (adjusted hazard ratio, 3.35; 95% CI, 1.87 to 6.00; P<0.001). A total of 467 and 395 serious adverse events were reported in the aspirin group and placebo group, respectively. CONCLUSIONS:Among patients with chronic coronary syndrome at high atherothrombotic risk who were receiving an oral anticoagulant, the addition of aspirin led to a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than placebo, as well as higher risks of death from any cause and major bleeding. (Funded by the French Ministry of Health and Bayer Healthcare; ClinicalTrials.gov number, NCT04217447.).

Objective To investigate the association between joint manifestations of vascular ageing (VA) and hypertension. Methods We used baseline (2008-2012) and follow-up data (up to 2024) from the Paris Prospective Study III, a French cohort of 10,157 participants. Prevalent and incident hypertension were determined at baseline (blood pressure ≥140/90 mmHg or on medication) and at 2, 4, 6, 8 and 10 years of follow-up (self-reported antihypertensive treatment). VA manifestations were assessed at baseline via echo-tracking in the right common carotid artery. Clustering analysis identified patterns of VA and their association with hypertension was assessed with logistic regression. Results The cross-sectional analysis included 9,096 participants (mean age: 59±6 years, 39% female). Hypertension prevalence was 36% (n=3,276). Three clusters of VA manifestations were identified. Cluster 1 (n=4,326;47.6%) was characterized by healthy vascular ageing (HVA), Cluster 2 by increased arteriosclerosis (ART) (n=2,274;25.0%) and Cluster 3 by greater atherosclerosis prevalence (ATH) (n=2,496;27.4%). Compared to the HVA cluster, ART (aOR 3.94; 95% CI 3.50;4.45) and ATH clusters (aOR 2.69; 95% CI 2.38;3.04) were associated with prevalent hypertension. The prospective analysis included 5,310 normotensives with 754 (14.1%) cases of incident hypertension (median follow-up of 10.05 years [range: 10.00;10.15]). Both ART (aOR 1.34; 95% CI 1.08;1.65) and ATH (aOR 1.70; 95% CI 1.40;2.07) clusters were associated with incident hypertension. Conclusion Vascular ageing manifestations reflecting increased carotid arteriosclerosis and atherosclerosis are related to prevalent and incident hypertension.

BACKGROUND AND AIMS:There is a variety of smoking habits trajectories in patients with established stable coronary artery disease (CAD), with unclear consequences on cardiovascular (CV) events. We aimed to clarify the impact of smoking cessation and reduction on long-term cardiovascular outcomes in stable CAD patients, evaluating whether quitting at any stage still provides significant benefits and to what extent. METHODS:The CLARIFY registry included 32,378 outpatients with stable CAD. Smoking history and status were recorded annually during the 5-year follow-up. In active smokers, we studied the effect of smoking cessation or reduction. In former smokers, we analysed the timing of smoking cessation relative to CAD diagnosis and residual CV risk based on years of abstinence. The primary outcome was a composite of CV death and MI. RESULTS:At inclusion, 46.2% of patients were former smokers and 12.5% current smokers. Amongst active smokers, smoking cessation in the stable phase of the disease was associated with improved outcomes, irrespective of timing (aHR 0.56, 95%CI 0.42-0.76, p<0.001). However, smoking quantity reduction was not associated with improved CV outcomes. Among former smokers, 55.7% had quit within a year of CAD diagnosis. Each additional year of smoking post-CAD diagnosis increased CV risk. Former smokers never returned to the CV risk level of never smokers, regardless of years of abstinence. CONCLUSIONS:In stable CAD patients, smoking cessation is associated with significantly better CV outcomes and survival, irrespective of timing of cessation, and should therefore always be a priority. Smoking reduction was not associated with improved CV outcomes. Most former smokers quit within a year of CAD diagnosis, and CV risk increase with each subsequent year of active smoking.

BACKGROUND AND IMPORTANCE:Acute pulmonary oedema is a frequent and potentially life-threatening emergency. Its management targets four key objectives: improving oxygenation, reducing volume overload, maintaining adequate blood pressure, and treating the underlying cause. Severe cases are mainly handled by cardiologists, emergency physicians, and intensivists, which may lead to variations in care and thus nonadherence to guidelines. OBJECTIVE:To evaluate interspecialty differences in the management of patients with severe acute pulmonary oedema and compare physicians' practices to 2021 European guidelines. DESIGN:A national cross-sectional survey using clinical vignettes. SETTINGS AND PARTICIPANTS:Four clinical vignettes, developed by a multidisciplinary scientific committee representing French cardiology, emergency medicine, and intensive care societies were distributed between June and September 2022 to physicians from the three specialties and to a panel of 20 experts. OUTCOME MEASURES AND ANALYSIS:The primary outcome was adherence to European guidelines. Interspecialty differences and predictors of nonadherence were assessed using univariate and multivariate analyses. MAIN RESULTS:A total of 1048 physicians responded (59% emergency physicians, 22% intensivists, and 19% cardiologists). Adherence rates were 66, 65, 69, and 76%, respectively among cardiologists, emergency physicians, intensivists, and experts. Intensivists and emergency physicians were more prone to initiate noninvasive ventilation than cardiologists (respectively 87, 82, and 71%, P  < 0.001 and P  < 0.01). Intensivists and cardiologists were more likely to intubate patients than emergency physicians (respectively 73, 65, and 43%, P  < 0.001 for both comparisons). Cardiologists more frequently administered intravenous diuretics (98%) compared with emergency physicians and intensivists (both 90%, P  = 0.002). Emergency physicians chose more frequently the correct door-to-balloon delay than cardiologists for ST-segment elevation myocardial infarction-related acute pulmonary oedema (43 versus 28%, P  = 0.003). Multivariate analysis showed lower adherence among physicians compared with experts. Adherence was also lower among physicians older than 40 years and those working in nonuniversity hospitals. CONCLUSIONS:This nationwide survey highlights marked discrepancies between European guidelines and clinical practice in the management of acute pulmonary oedema, with substantial variation across specialties regarding initiation of oxygen therapy, invasive ventilation, nitrates, or delay for thrombolysis of an ST-segment elevation myocardial infarction.

Background The management of myocardial infarction without ST segment elevation (NSTEMI) in elderly patients remains challenging, in particular the benefit/risk balance of routine revascularization remains uncertain. Study design EVAOLD is s a multicenter, prospective, open-label trial with 2 parallel arms in NSTEMI patients >= 80 years of age. The aim of the trial is to test whether a strategy of selective invasive management guided by ischemia stress imaging (IMG group) will be noninferior in preventing Major Adverse Cardiac and Cerebrovascular Events (MACCE, ie all-cause death, nonfatal myocardial infarction, nonfatal stroke) rates at 1 year compared with a routine invasive strategy (INV Group). Geriatric assessment and cost- effectiveness analysis will also be performed. A sample size of 1,756 patients (assuming a 10% rate of patients lost to follow-up) is needed to show noninferiority with 80% power. Noninferiority based on exponential survival curves will be declared if the upper limit of the 1-sided 97.5% confidence interval for the hazard ratio is lower than 1.24, corresponding to a noninferiority margin of 7% in absolute difference and an event rate of 40% in the INV group. Conclusion EVAOLD is a nationwide, prospective, open-label trial testing the noninferiority of a strategy of selective invasive management guided by ischemia stress imaging versus routine invasive strategy in elderly NSTEMI patients. ClinicalTrials.gov Identifier: NCT03289728. (Am HeartJ 2025;279:94-103.)

Introduction Several cardiovascular outcome trials have been conducted to assess the cardiovascular safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RAs) on cardiorenal outcomes in patients with type-2 diabetes (T2D). However, the strict requirements of randomised controlled trials to avoid most confounding factors are at the expense of external validity. Using national real-world data, we aimed to evaluate the effectiveness of GLP-1RAs in association with metformin especially on cardiovascular events, hospitalisation for heart failure and all-cause death in comparison with other diabetes treatment schemes using dipeptidyl peptidase IV inhibitors, sulfonylureas/glinides or insulin also associated with metformin. Sodium-glucose transport protein 2 inhibitors (SGLT-2i) will be excluded as comparators, as this class of oral hypoglycaemic agents just started in 2020 to be marketed in France.Methods and analysis The Système National des Données de Santé is a comprehensive nationwide administrative healthcare database in France that covers approximately 67 million people.Several cohorts of adult patients with T2D initiating any GLP1-RA in dual or triple therapies, as recommended by the French Health authorities, will be identified in this database over the period 2016–2021. These cohorts will be defined by the combination of glucose-lowering drugs prescribed simultaneously with GLP1-RA and diabetes treatment received over a 6-month period before GLP1-RA initiation. They will be first matched with T2D controls (1:3 ratio) based on the year of drug initiation and treatment regimens before and simultaneously with GLP1-RA in the different selected cohorts. Comparative analyses will be conducted versus these control groups, adjusting for cardiovascular event history and a propensity score considering age, sex, area of residence, deprivation index, comorbidities, duration of diabetes, use of lipid-lowering drugs, anticoagulants, antiplatelet therapies and blood pressure-lowering therapies. Comparative analyses will be conducted versus these control groups, using a high-dimensional propensity scores method and fixed baseline characteristics. Treatment effects on the different outcomes measured will be estimated for each GLP1-RA group, through HR and their corresponding CIs (95% CI) using Cox regressions and/or competitive risk regressions when necessary.Ethics and dissemination The study has been approved by an independent ethics committee (Comité éthique et scientifique pour les recherches, les études et les évaluations dans le domaine de la santé, Paris, France; reference: 8699786, dated 2 June 2022) and has been registered with the French National Data Protection Commission (Commission Nationale de l'Informatique et des Libertés, Paris, France; reference: 922161, dated 26 June 2022). The findings of this study will be published in peer-reviewed scientific journals and presented at international conferences.Trial registration number F20220803152803.

BACKGROUND:Patients with atrial fibrillation treated with oral anticoagulants are at risk of bleeding. AIM:To describe oral anticoagulant-treated patients with atrial fibrillation who experience bleeding events requiring hospitalization, treatment patterns and outcomes following the bleeding event. METHODS:This was a retrospective cohort study using the French national health system claims database, analysing patients with atrial fibrillation newly treated with an oral anticoagulant, with at least one hospitalization for bleeding between 2014 and 2016, followed up to December 2019. Sites of bleeding, sociodemographic and clinical characteristics, treatment patterns before and after the first bleeding event, the number of bleeding events over follow-up, the time from index date to first bleed and the time from first bleed to death are described. RESULTS:Among 321,346 patients, 12,616 (3.9%) experienced at least one bleeding event (34.9% gastrointestinal). The median follow-up was 3.6 years from the index inclusion and 3.0 years from the first bleed. The mean age was 79.1 years, the mean Charlson Comorbidity Index score was 6.2 and 72% had modified HAS-BLED scores≤3. Before the first bleed, 9.2% of patients had switched from the index oral anticoagulant to another oral anticoagulant, and 6.6% had stopped oral anticoagulant treatment. After the first bleed, 43.6% remained treated with the same oral anticoagulant, 5.2% switched to another oral anticoagulant and 31.7% received no oral anticoagulant. Most patients experienced only one bleeding event; the median time from first bleed to death was 9.3 months. CONCLUSIONS:These "real-life" data show that patients with atrial fibrillation who experience a bleeding event have a high co-morbidity score, but often a low modified HAS-BLED score. The data document treatment patterns before and after bleeding, and show that in patients treated with oral anticoagulants, bleeding is associated with a high subsequent risk of death.