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cohorts have shown that regular aerobic exercise may also improve AF-related symptoms, quality of life, and exercise capacity.142,143 Better cardiorespiratory fitness and a gain in cardiorespiratory fitness over time are associated with a greater reduction in AF burden and improved maintenance of sinus rhythm.141–145

5.7 Alcohol excess

Alcohol consumption can increase the risk of adverse events in patients with AF, such as thromboembolism, death, or AF-related hospitalization.231,232 Alcohol is associated with an increased risk of ischaemic stroke in patients with newly diagnosed AF, and alcohol abstinence after AF diagnosis can reduce the risk of ischaemic stroke.233 In patients receiving OAC, alcohol excess is associated with a greater risk of bleeding,234 mediated by poor adherence, alcohol–drug interactions, liver disease, and variceal bleeding. Alcohol consumption is associated with a dose-dependent increase in the recurrence of AF after catheter ablation.147,235 In an RCT among regular non-binge drinkers with AF, the goal of abstinence led to a significant reduction in AF recurrence and burden; alcohol intake was reduced from 16.8 to 2.1 standard drinks per week (≤30 grams or 3 standard drinks of alcohol) in the intervention arm, with 61% attaining abstinence.147 In observational data of patients undergoing catheter ablation, reduction of consumption to ≤7 standard drinks (≤70 grams of alcohol) per week was associated with improved maintenance of sinus rhythm.128,235

6 [A] Avoid stroke and thromboembolism

6.1 Initiating oral anticoagulation

Atrial fibrillation is a major risk factor for thromboembolism, irrespective of whether it is paroxysmal, persistent, or permanent.236,237 Left untreated, and dependent on other patient-specific factors, the risk of ischaemic stroke in AF is increased five-fold, and one in every five strokes is associated with AF.238 The default approach should therefore be to provide OAC to all eligible patients, except those at low risk of incident stroke or thromboembolism. The effectiveness of OAC to prevent ischaemic stroke in patients with AF is well established.239,240 Antiplatelet drugs alone (aspirin, or aspirin in combination with clopidogrel) are not recommended for stroke prevention in AF.241,242

6.1.1 Decision support for anticoagulation in AF

Tools have been developed to enable easier implementation of OAC in patients with clinical AF. The majority of OAC clinical trials have used variations of the CHADS2 score to indicate those at risk (with points for chronic heart failure, hypertension, age, diabetes, and 2 points for prior stroke/transient ischaemic attack [TIA]). Although most available stroke risk scores are simple and practical, the predictive value of scores is generally modest (see Supplementary data online, Table S3).243–245 Classification and discrimination of adverse events is relatively poor for all scores and hence the benefit of using them to select patients for OAC is unclear. There is also considerable variation in the definition of risk factors across countries,246 and a lack of evidence from clinical trials on the ability of stroke risk scoring to enhance clinical practice.243 This guideline continues to provide a Class IA recommendation for the use of OAC in patients at risk of thromboembolism. However, in the absence of strong evidence for how to apply risk scores in real-world patients, this has been separated from the use of any particular risk score. This is also in line with regulatory approvals for direct oral anticoagulants (DOACs), which do not stipulate risk scores or numerical thresholds.25–28,245

Substantive changes have occurred in the decades since these risk scores were developed in regards to population-level risk factor profiles, therapies, and targets.198 Historical scores do not take into account parameters that have been associated with thromboembolism in contemporary cohorts, such as cancer, chronic kidney disease (CKD), ethnicity, and a range of circulating biomarkers (including troponin and B-type natriuretic peptide [BNP]). As an example, for CKD there is a correlation between decreasing glomerular filtration rate and proteinuria with stroke risk,247–250 and cohort data suggest a twofold increased risk of ischaemic stroke and mortality in AF patients with CKD vs. without.251 Other factors, such as atrial enlargement, hyperlipidaemia, smoking, and obesity, have been identified in specific cohort studies as additional risk factors for ischaemic stroke in AF.70,252,253 Biomarkers, such as troponin, natriuretic peptides, growth differentiation factor-15, cystatin C, and interleukin-6, can also indicate residual stroke risk among anticoagulated AF patients.254,255 Biomarker-guided stroke prevention is currently being evaluated in an ongoing RCT (NCT03753490). Until further validation within RCTs is available, this task force continues to support using simple clinical classification for implementation of OAC. Clinicians should use tools that have been validated in their local population and take an individualized approach to thromboembolic risk stratification that considers the full range of each patient’s specific risk factors. The absolute risk level at which to start OAC in individual patients cannot be estimated from populationlevel studies. It will vary depending on how those factors interact with other medical issues, and the degree of risk acceptable or tolerated by that person. In general, most of the available risk scores have a threshold of 0.6%–1.0% per annum of thromboembolic events for clinical AF to warrant OAC prescription. Across Europe, the most popular risk score is CHA2DS2–VASc, giving points for congestive heart failure, hypertension, age ≥75 years (2 points), diabetes mellitus, prior stroke/TIA/thromboembolism (2 points), vascular disease, age 65–74 years and female sex. However, implementation has varied in terms of gender. Female sex is an age-dependent stroke risk modifier rather than a risk factor per se.112,256,257 The inclusion of gender complicates clinical practice both for healthcare professionals and patients.258 It also omits individuals who identify as non-binary, transgender, or are undergoing sex hormone therapy. Previous guidelines from the ESC (and globally) have not actually used CHA2DS2-VASc; instead providing different score levels for women and men with AF to qualify for OAC. Hence, CHA2DS2-VA (excluding gender) has effectively been in place (Table 10).78 This task force proposes, in the absence of other locally validated alternatives, that clinicians and patients should use the CHA2DS2-VA score to assist in decisions on OAC therapy (i.e. without a criterion for birth sex or gender). Pending further trials in lower risk patients (NCT04700826,259 NCT02387229260), OAC are recommended in those with a CHA2DS2-VA score of 2 or more and should be considered in those with a CHA2DS2-VA score of 1, following a patient-centred and shared care approach. Healthcare professionals should take care to assess for other thromboembolic risk factors that may also indicate the need for OAC prescription.

ESC Guidelines                                                                                                                                                                                          3341

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