Aims Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. Methods and results This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Conclusions Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI.

Aims The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes. Methods and results This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence. Conclusion The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related proplems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.

ObjectiveThere has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation (AF). This review identified and systematically evaluated literature on clinical and economic outcomes of inappropriate NOAC dosing and associated patient characteristics.MethodsMEDLINE, Embase, Cochrane Library, International Pharmaceutical Abstracts, Econlit, PubMed and NHS EEDs databases were searched for English language observational studies from all geographies published between 2008 and 2020, examining outcomes of, or factors associated with, inappropriate NOAC dosing in adult patients with AF.ResultsOne hundred and six studies were included in the analysis. Meta-analysis showed that compared with recommended NOAC dosing, off-label underdosing was associated with a null effect on stroke outcomes (ischaemic stroke and stroke/transient ischaemic attack (TIA), stroke/systemic embolism (SE) and stroke/SE/TIA). Meta-analysis of 15 studies examining clinical outcomes of inappropriate NOAC dosing found a null effect of underdosing on bleeding outcomes (major bleeding HR=1.04, 95% CI 0.90 to 1.19; p=0.625) but an increased risk of all-cause mortality (HR=1.28, 95% CI 1.10 to 1.49; p=0.006). Overdosing was associated with an increased risk of major bleeding (HR=1.41, 95% CI 1.07 to 1.85; p=0.013). No studies were found examining economic outcomes of inappropriate NOAC dosing. Narrative synthesis of 12 studies examining drivers of inappropriate NOAC dosing found that increased age, history of minor bleeds, hypertension, congestive heart failure and low creatine clearance (CrCl) were associated with an increased risk of underdosing. There was insufficient evidence to assess drivers of overdosing.ConclusionsOur analysis suggests that off-label underdosing of NOACs does not reduce bleeding outcomes. Patients prescribed off-label NOAC doses are at an increased risk of all-cause mortality. These data underscore the importance of prescriber adherence to NOAC dosing guidelines to achieve optimal clinical outcomes for patients with AF.PROSPERO registration numberCRD42020219844.

Background Anticoagulation therapy with vitamin K antagonists (e.g. warfarin) has recently been shown to contribute to the accelerated vascular calcification and worsening of renal function. Therefore, it is compelling to investigate the impact of different oral anticoagulants (OACs) on kidney function in non-valvular atrial fibrillation (NVAF) patients. Common co-morbidities in these patients are chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM), which might be presented at the OAC therapy initiation. Purpose The overall objective of the CALLIPER study was to evaluate the effectiveness and safety of the reduced dose rivaroxaban (15 mg once daily) as compared to warfarin in NVAF patients with renal dysfunction in real-world setting. In particular, we evaluated the risk of worsening of renal function in NVAF patients with CKD stage 3 and 4 at baseline (1 year prior to the cohort entry). Additionally, a sub-group analysis of patients with T2DM was performed. We defined worsening of renal function as progression to CKD stage 5, kidney failure or need for dialysis. Methods Individual level data of warfarin- and rivaroxaban-naïve NVAF patients from the MarketScan database for the years 2012 through 2017 were used. Patients with moderate-to-severe CKD (stage 3 and 4) were included in the study cohort and were followed until progression to CKD 5, kidney failure or dialysis, OAC discontinuation/switch, insurance disenrollment or end of data availability. A comparative analysis evaluating the hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) under warfarin or rivaroxaban treatment was performed using Cox regression. A stabilized inverse probability of treatment weighting was used to adjust for imbalances in baseline patient characteristics. Results We identified 5,906 warfarin- and 1,466 rivaroxaban-naïve patients with NVAF and CKD stage 3 and 4, of which 60% were male, median (25–75% range) age=79 (71- 84) years, CHADS2 score=2.67 (2.00- 3.50), CHA2DS2-VASc score=4.43 (3.40–5.62), modified HAS-BLED score=3.00 (2.40 - 3.65). T2DM was present in more than 50% of patients (Table), namely, in 3,160 warfarin- and 746 rivaroxaban-users. Hazard ratios and 95% CI for worsening of renal function were evaluated at 0.53 (0.35; 0.78) in the main cohort and 0.50 (0.30; 0.83) in the T2DM sub-group, meaning that rivaroxaban was associated with a significant 47% and 50% risk reduction of this outcome in NVAF patients with CKD stage 3 and 4 with and without T2DM, respectively. Conclusion The reduced dose of rivaroxaban has appeared to lower significantly the risk of worsening of renal function versus warfarin in NVAF patients with CKD stage 3 and 4 present at the OAC therapy initiation. The conclusion holds true for the patients with the co-morbid T2DM. This evidence was generated by the CALLIPER study using one of the largest US administrative claims database. Acknowledgement/Funding CI Coleman has received research grants from Bayer AG

Background Diabetes increases a patient’s risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes. Methods This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression. Results We included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88–0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86–0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66–1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89–0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55–0.72). Conclusions In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.