The impact of some risk factors for stroke and bleeding, and the value of stroke and bleeding risk scores, in atrial fibrillation (AF), has been debated, as clinical trial cohorts have not adequately tested these. Our objective was to investigate risk factors for stroke and bleeding in AF, and application of the new CHA₂DS₂-VASc and HAS-BLED schemes for stroke and bleeding risk assessments, respectively. We used the Swedish Atrial Fibrillation cohort study, a nationwide cohort study of 182 678 subjects with a diagnosis of AF at any Swedish hospital between 1 July 2005 and 31 December 2008, who were prospectively followed for an average of 1.5 years (260 000 years at risk). With the use of the National Swedish Drug Registry, all patients who used an oral anticoagulant anytime during follow-up were identified. Most of the analyses were made on a subset of 90 490 patients who never used anticoagulants. Risk factors for stroke, the composite thromboembolism endpoint (stroke, TIA, or systemic embolism), and bleeding, and the performance of published stroke and bleeding risk stratification schemes were investigated. On multivariable analysis, significant associations were found between the following ‘new’ risk factors and thromboembolic events; peripheral artery disease [hazard ratio (HR) 1.22 (95% CI 1.12–1.32)], ‘vascular disease’ [HR 1.14 (1.06–1.23)], prior myocardial infarction [HR 1.09 (1.03–1.15)], and female gender [HR 1.17 (1.11–1.22)]. Previous embolic events, intracranial haemorrhage (ICH), hypertension, diabetes, and renal failure were other independent predictors of the composite thromboembolism endpoint, while thyroid disease (or hyperthyroidism) was not an independent stroke risk factor. C-statistics for the composite thromboembolic endpoint with the CHADS₂ and CHA₂DS₂-VASc schemes were 0.66 (0.65–0.66) and 0.67 (0.67–0.68), respectively. On multivariable analysis, age, prior ischaemic stroke or thromboembolism, prior major bleeding events, and hypertension were significant predictors of ICH and major bleeding. Heart failure, diabetes, renal failure, liver disease, anaemia or platelet/coagulation defect, alcohol abuse, and cancer were other significant predictors for major bleeding, but not ICH. The ability for predicting ICH and major bleeding with both bleeding risk schemes (HEMORR₂HAGES, HAS-BLED) were similar, with c-statistics of ∼0.6. Several independent risk factors (prior ICH, myocardial infarction, vascular disease, and renal failure) predict ischaemic stroke and/or the composite thromboembolism endpoint in AF, but thyroid disease (or hyperthyroidism) was not an independent risk factor for stroke. There is a better performance for CHA₂DS₂-VASc over CHADS₂ schemes for the composite thromboembolism endpoint. While both tested bleeding risk schemes have similar predictive value, the HAS-BLED score has the advantage of simplicity.

The risk of stroke is heterogeneous across different groups of patients with atrial fibrillation (AF), being dependent on the presence of various stroke risk factors. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Systematic literature reviews were conducted to identify relevant articles published from the last formal search perfomed for the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). The overall quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted, voted on, and revised until consensus was reached. For patients with AF without valvular heart disease, including those with paroxysmal AF, who are at low risk of stroke (eg, CHA₂DS₂-VASc [congestive heart failure, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)] score of 0 in males or 1 in females), we suggest no antithrombotic therapy. The next step is to consider stroke prevention (ie, oral anticoagulation therapy) for patients with 1 or more non-sex CHA₂DS₂-VASc stroke risk factors. For patients with a single non-sex CHA₂DS₂-VASc stroke risk factor, we suggest oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel; and for those at high risk of stroke (eg, CHA₂DS₂-VASc ≥ 2 in males or ≥ 3 in females), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest using a non-vitamin K antagonist oral anticoagulant drug rather than adjusted-dose vitamin K antagonist therapy. With the latter, it is important to aim for good quality anticoagulation control with a time in therapeutic range > 70%. Attention to modifiable bleeding risk factors (eg, uncontrolled BP, labile international normalized ratios, concomitant use of aspirin or nonsteroidal antiinflammatory drugs in an anticoagulated patient, alcohol excess) should be made at each patient contact, and HAS-BLED (hypertension, abnormal renal/liver function [1 point each], stroke, bleeding history or predisposition, labile international normalized ratio, elderly (0.65), drugs/alcohol concomitantly [1 point each]) score used to assess the risk of bleeding where high risk patients (≥ 3) should be reviewed and followed up more frequently. Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF with ≥1 non-sex CHA₂DS₂-VASc stroke risk factor(s).

Atrial fibrillation (AF) is the most common cardiac arrhythmia despite substantial efforts to understand the pathophysiology of the condition and develop improved treatments. Identifying the underlying causative mechanisms of AF in individual patients is difficult and the efficacy of current therapies is suboptimal. Consequently, the incidence of AF is steadily rising and there is a pressing need for novel therapies. Research has revealed that defects in specific molecular pathways underlie AF pathogenesis, resulting in electrical conduction disorders that drive AF. The severity of this so-called electropathology correlates with the stage of AF disease progression and determines the response to AF treatment. Therefore, unravelling the molecular mechanisms underlying electropathology is expected to fuel the development of innovative personalized diagnostic tools and mechanism-based therapies. Moreover, the co-creation of AF studies with patients to implement novel diagnostic tools and therapies is a prerequisite for successful personalized AF management. Currently, various treatment modalities targeting AF-related electropathology, including lifestyle changes, pharmaceutical and nutraceutical therapy, substrate-based ablative therapy, and neuromodulation, are available to maintain sinus rhythm and might offer a novel holistic strategy to treat AF.