Real-world Atrial Fibrillation Patients Research Articles

Percutaneous left atrial appendage occlusion and risk of stroke, hospitalized bleeding and death in Medicare beneficiaries.

Among patients with atrial fibrillation (AF), a nonpharmacologic option (e.g., percutaneous left atrial appendage occlusion [LAAO]) is needed for patients with oral anticoagulant (OAC) contraindications. Among beneficiaries in the Medicare fee-for-service coverage 20% sample databases (2015-18) who had AF and an elevated CHA2DS2-VASc score, we assessed the association between percutaneous LAAO versus OAC use and risk of stroke, hospitalized bleeding, and death. Patients undergoing percutaneous LAAO were matched to up to five OAC users by sex, age, date of enrollment, index date, CHA2DS2-VASc score, and HAS-BLED score. Overall, 17 156 patients with AF (2905 with percutaneous LAAO) were matched (average ± SD 78 ± 6 years, 44% female). Cox proportional hazards model were used. Median follow-up was 10.3 months. After multivariable adjustments, no significant difference for risk of stroke or death was noted when patients with percutaneous LAAO were compared with OAC users (HRs [95% CIs]: 1.14 [0.86-1.52], 0.98 [0.86-1.10]). There was a 2.94-fold (95% CI: 2.50-3.45) increased risk for hospitalized bleeding for percutaneous LAAO compared with OAC use. Among patients 65 to <78 years old, those undergoing percutaneous LAAO had higher risk of stroke compared with OAC users. No association was present in those ≥78 years. In this analysis of real-world AF patients, percutaneous LAAO versus OAC use was associated with similar risk of death, nonsignificantly elevated risk of stroke, and an elevated risk of bleeding in the post-procedural period. Overall, these results support results of randomized trials that percutaneous LAAO may be an alternative to OAC use for patients with contraindications.

Pulsed field ablation in real-world atrial fibrillation patients: clinical recurrence, operator learning curve and re-do procedural findings.

Pulsed field ablation (PFA) is a novel method of cardiac ablation demonstrated in early pre-clinical and clinical settings. The aim of this study was to report the safety and clinical efficacy of pulmonary vein isolation (PVI) with PFA for real-world atrial fibrillation (AF) patients. All-comer AF patients (n = 121, 59% paroxysmal) were prospectively included and underwent PFA with 100% high-density voltage maps performed after PVI. Clinical outcomes were gathered by chart review. PVI was achieved with PFA-only in 119 (98%) of the cases. During the implementation phase the mean procedure and fluoroscopy time was reduced from 85 ± 34 to 72 ± 18min (p = 0.044) and 22 ± 9 to 16 ± 4 (p = 0.034). We observed one phrenic nerve palsy with only partial remission at follow-up. Other adverse events were numerically comparable to standard PVI procedures. Over a mean follow-up of 308 ± 87days, a total of 22/121 (18.2%) cases experienced clinically significant recurrence or initiation of anti-arrhythmic drugs with Kaplan-Meier event-free estimate at 365days of 80% (88% for paroxysmal versus 69% for persistent). In five of eight re-do procedures, gaps were primarily located at the right pulmonary veins. PFA was a highly efficient method to achieve PVI with reductions in procedure time and fluoroscopy over the implementation period. The procedural data and clinical recurrence rates from initial trials were confirmed in real-life non-selected AF patients. More data is needed to establish lesion durability and limitations of PFA.

Machine learned clusters explain heterogeneity in outcomes from map-guided ablation of Atrial Fibrillation results from the large PROspective STanford AF Registry (ProSTAR)

Abstract Background Several mapping systems are being introduced to guide atrial fibrillation (AF) ablation to patient-specific regions of interest. However, results have been extremely heterogeneous between studies, ranging from very poor to very promising. It is unknown if this reflects specific patient characteristics or procedural factors because most prior series were middle sized (N∼30–100 patients). Purpose To study 1 year and 3 year very long-term outcomes from map guided AF-driver ablation in a large patient registry with multiple operators, to identify clinical and procedural features influencing outcomes. In real-world AF patients with diverse comorbidities, we applied a consistent patient-tailored AF mapping and ablation strategy, monitored outcomes carefully and applied statistical and unsupervised machine learning approaches to identify features of success and failure. Method We studied 632 consecutive patients (65±10 y, 178 F) undergoing ablation for drug-refractory AF. 59.7% had persistent AF, and 29.9% had prior unsuccessful ablation (median 1 procedure). All patients underwent pulmonary vein isolation (PVI), followed by ablation of AF regions of interest mapped from 64 pole baskets (RhythmView, Abbott, IL), by 11 operators. Patients were followed using ambulatory ECG monitors quarterly for one year, and at the time of symptoms for 3 years. Results Fig. 1A shows overall freedom from AF at 1-year of 77.5% (95% CI: 74.2%, 80.9%) and at 3 years of 55.5% (95% CI: 51.2%, 60.1%). Freedom from AF/AT at 1-year was 70.1% (95% CI: 66.5%, 73.8%), and at 3 years was 48.6% (95% CI: 44.3%, 53.3%). Success was higher in patients with procedural termination, first ablation versus prior unsuccessful procedures, for paroxysmal AF than non-paroxysmal AF (1 year: AT/AF freedom 74.9% versus 66.7%, p=0.006), and smaller left atrium. Three clusters (Fig 1B) were identified comprising CHA2DS2VASc score, enlarged LA, prior failed case, presenting rhythm and termination during the procedure (Table 2). At 1 year, freedom from AT/AF was 77.8% (95% CI: 72.2%, 82.1%) for cluster 3 and 56.2% (95% CI: 48.3%, 65.4%) for cluster 1 (Fig. 1B). Conclusion In our large registry of N=632 patients undergoing AF-map guided ablations, machine learned clusters identified cohorts with success of 56.2 to 77.8% at 1 year. Future studies should identify if lower success represents technical challenges, such as difficulties in mapping very large atria, or more difficult to treat mechanisms. These results may inform patient inclusion and ablation strategy in upcoming AF treatment trials. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National budget only - NIH, R01 HL149134, R01HL83359

Long-Term Results of Pulmonary Vein Isolation Plus Modified Posterior Wall Debulking Utilizing High-Power Short-Duration Strategy: An All-Comers Study in Real World.

Background:High-power short-duration radiofrequency ablation has improved lesion durability in pulmonary vein isolation. In this study, we investigate long-term clinical outcomes of high-power short-duration pulmonary vein isolation and posterior wall debulking as an initial treatment modality in all corner atrial fibrillation patients.Methods:This is a single-center, retrospective, observational study including all patients who have undergone high-power short-duration pulmonary vein and posterior wall debulking, regardless of atrial fibrillation type and/or duration. High-power short-duration power delivery protocol was defined as 45 W at all ablation sites. Clinical and electrocardiographic follow-up were performed in all patients.Results:One hundred forty-two patients were enrolled in this study. Paroxysmal atrial fibrillation was present in 88 (62%) of patients. The mean follow-up of this study was 36.9 months ± 12.2 months. During the follow-up period, 10 patients (11.4%) with a diagnosis of paroxysmal atrial fibrillation had recurrence, while recurrence in patients with persistent and long-standing persistent atrial fibrillation was slightly higher (15 patients (28.1%) and 5 patients (50%), respectively). No major life-threatening complications occurred.Conclusion:This study has demonstrated excellent arrhythmia-free outcomes in unselected, real world atrial fibrillation patients undergoing high-power short-duration pulmonary vein and debulking posterior wall isolations, however larger randomized trials are warranted.

The Atrial Fibrillation Better Care (ABC) Pathway and Clinical Outcomes in Patients with Atrial Fibrillation: the Prospective Murcia AF Project Phase II Cohort

ABSTRACTBackgroundThe Atrial fibrillation Better Care (ABC) pathway was proposed for a more holistic or integrated care approach to atrial fibrillation (AF) management. We investigated whether adherence with the ABC pathway reduced the risk of adverse clinical outcomes in real-world AF patients starting vitamin K antagonist (VKAs) therapy.MethodsProspective cohort study including AF outpatients starting VKA therapy from July 2016 to June 2018. Patients were considered as adherent if all ABC pathway criteria (A: Avoid stroke; B: Better symptom control; and C: Cardiovascular risk factors/comorbidities management) were fulfilled. The primary endpoints were all-cause mortality, net clinical outcomes (NCOs), major adverse cardiovascular events (MACE), and composite thrombotic/thromboembolic events at 2 years.ResultsWe enrolled 1045 patients (51.6% female; median age 77 [70–83] years). Of these, 63.0% (658) were adherent to the ABC pathway and 37% (387) were considered non-adherent. Compared to non-adherent patients, those who were ABC adherent had lower event rates for all-cause mortality (13.76 vs. 6.56; p<0.001), NCOs (19.65 vs. 11.94; p<0.001), and MACE (11.88 vs. 7.75; p=0.006) during the follow-up. Adjusted Cox regression analyses demonstrated that the ABC pathway adherent care reduced the risks of all-cause mortality (aHR 0.57, 95% CI 0.42–0.78), NCOs (aHR 0.72, 95% CI 0.56–0.92), and cardiovascular mortality (aHR 0.54, 95% CI 0.32–0.90). Event-free survivals for all-cause mortality, NCOs (both log-rank p-values <0.001), and MACE (log-rank p-value = 0.004) were also higher in ABC pathway adherent patients.ConclusionsIn this real-world prospective cohort of AF patients starting VKA therapy, adherence to the ABC pathway management at baseline significantly reduced the risk of NCOs, all-cause mortality, and cardiovascular death at 2 years.

Safety and efficacy of apixaban and rivaroxaban versus warfarin in real-world atrial fibrillation patients are similar to their randomized trials: insights from GARFIELD-AF registry

Abstract Introduction Generalisability of patient selection in the landmark trials for the approval of apixaban (ARISTOTLE) and rivaroxaban (ROCKET AF) for use in non-valvular atrial fibrillation (AF) is limited. Although observational data have confirmed the safety and efficacy of these non-vitamin K oral anticoagulants (NOACs) in unselected AF populations, robust replication of randomized trials in observational studies is warranted. Purpose To investigate the proportion of real-world AF patients who would have been eligible for the landmark trials for ARISTOTLE and ROCKET AF, and to assess reproducibility of these landmark trials in the largest, worldwide, prospective registry of newly diagnosed AF patients. Methods We analysed data from the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) registry. We assessed the eligibility of AF patients treated with apixaban or vitamin K antagonist (VKA) for ARISTOTLE, and those treated with rivaroxaban or VKA for ROCKET AF, using the selection criteria of the original trials. We replicated the inclusion and exclusion criteria of ARISTOTLE and ROCKET AF by deriving the set of patients eligible for each trial and calculating the adjusted hazard ratios (HRs) for stroke or systemic embolism, major bleeding, and all-cause mortality within 2 years of enrolment, using a propensity score overlap weighted Cox model. We compared the results from observational data with those reported in the original ARISTOTLE and ROCKET AF publications. Results Among all patients enrolled in GARFIELD-AF, 67% were eligible for recruitment in ARISTOTLE and 37% in ROCKET AF. The corresponding proportions among anticoagulated patients were 70% and 39%, respectively. Among patients on apixaban and VKA, 2570/3615 (71%) and 8005/11718 (68%), respectively, were eligible for ARISTOTLE. Of patients using rivaroxaban and VKA, 2005/4914 (41%) and 4368/11721 (37%), respectively, were eligible for ROCKET AF. Annual eligibility rates among real-world NOAC users were stable over time (Figure 1). Registry participants on rivaroxaban or VKA eligible for ROCKET AF had a higher burden of cardiovascular co-morbidity than those on apixaban or VKA eligible for ARISTOTLE. The adjusted HRs in observational data were compatible with results of the original trials in all selected outcomes (Figure 2). Conclusion Representativeness of ARISTOTLE and ROCKET AF for real-world AF populations was limited, with ROCKET AF's criteria being more restrictive. Despite inclusion of only incident AF cases in GARFIELD-AF versus mostly prevalent AF cases in the original trials, the results were similar. Our work indicates that the results from ARISTOTLE and ROCKET AF appear robust and reproducible in real-world patients with newly diagnosed AF. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the GARFIELD-AF registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

2MACE score predicts cardiovascular adverse events in real-world atrial fibrillation patients under rivaroxaban therapy. Data from EMIR study

Abstract Background Atrial Fibrillation (AF) patients have higher risk of major adverse cardiovascular events (MACEs). In 2015, the 2MACE score (2 points for metabolic syndrome and age ≥75, and 1 point for myocardial infarction [MI] or revascularization, congestive heart failure [ejection fraction ≤40%] and thromboembolism [stroke or transient ischemic attack]) was described to stratify cardiovascular risk and 2MACE≥3 was related with high risk of MACE in AF patients but a long-term validation in prospective patients under direct anticoagulants has not been performed yet. The aim of this study was to analyse the incidence of cardiovascular events and to validate the 2MACE score as predictor of MACEs. Methods EMIR study [acronym from 'Estudio observacional para la identificaciόn de los factores de riesgo asociados a eventos cardiovasculares Mayores en pacientes con fIbrilaciόn auricular no valvular tratados con un anticoagulante oral directo (Rivaroxaban)'] was an observational, multicenter, post-authorization and prospective study that involved AF patients under oral anticoagulation with rivaroxaban at least 6 months before enrolment. We analyzed baseline clinical characteristics and adverse events after 2.5 years of follow up: annual incidence of thromboembolic events, MACE (composite of nonfatal MI, coronary revascularization and cardiac death) and cardiovascular mortality were analyzed. Results We analyzed 1,433 patients (55.5% women, mean 74.2±9.7 years). 385 (26.9%) patients had 2MACE score ≥3 and of those high-risk patients, 42.1% had previous coronary disease, 12.5% had previous peripheral artery disease, 40.7% had diabetes mellitus, 39% heart failure and 50% had chronic kidney disease (GFR&amp;lt;60 ml/min). After 2.5 (2.2–2.6) years of follow-up, we observed patients with 2MACE score ≥3 had higher rate of adverse events (Table), specially of higher rate of cardiovascular mortality and MACE. Patients with 2MACE score ≥3 had RR 4.09 (2.59–6.45; p&amp;lt;0.001) for MACE. Indeed, patients with 2MACE score ≥3 had around 6-fold risk of cardiovascular death due heart failure than patients with 2MACE score &amp;lt;3 (0.17%/year vs 1.09%/year; p=0.003). 2MACE score had suitable predictive performance for MACE (AUC 0.638 [(0.534–0.742); p=0.010). Conclusion In a Real-world AF patients under rivaroxaban therapy from EMIR registry, the 2MACE score is a good predictor of long-term cardiovascular events, MACE and major bleeding. A 2MACE score ≥3 categorize patients at “high-risk” with almost 4-fold risk of MACE in a long-term follow-up. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer Hispania S.L. Table 1. Adverse events according to 2MACE

Characterization of atrial fibrillation in real-world patients: testing the 4S-AF scheme in the Spanish and French cohorts of the EORP-AF Long-Term General Registry.

The 4S-AF scheme [Stroke risk, Symptom severity, Severity of atrial fibrillation (AF) burden, Substrate severity] has recently been described as a novel approach to in-depth characterization of AF. We aim to determine if the 4S-AF scheme would be useful for AF characterization and provides prognostic information in real-world AF patients. The Spanish and French cohorts of the EORP-AF Long-Term General Registry were included. The baseline 4S-AF scheme was calculated and related to the primary management strategy (rhythm or rate control). Follow-up was performed at 1-year with all-cause mortality and the composite of ischaemic stroke/transient ischaemic attack/systemic embolism, major bleeding, and all-cause death, as primary endpoints. A total of 1479 patients [36.9% females, median age 72 interquartile range (IQR 64-80) years] were included. The median 4S-AF scheme score was 5 (IQR 4-7). The 4S-AF scheme, as continuous and as categorical, was associated with the management strategy decided for the patient (both P < 0.001). The predictive performances of the 4S-AF scheme for the actual management strategy were appropriate in its continuous [c-index 0.77, 95% confidence interval (CI) 0.75-0.80] and categorical (c-index 0.75, 95% CI 0.72-0.78) forms. Cox regression analyses showed that 'red category' classified patients in the 4S-AF scheme had a higher risk of all-cause death (aHR 1.75, 95% CI 1.02-2.99) and composite outcomes (aHR 1.60, 95% CI 1.05-2.44). Characterization of AF by using the 4S-AF scheme may aid in identifying AF patients that would be managed by rhythm or rate control and could also help in identifying high-risk AF patients for worse clinical outcomes in a 'real-world' setting.

Reduction of mortality by catheter ablation in real-world atrial fibrillation patients with heart failure

Whether catheter ablation for atrial fibrillation (AF) improves survival and affects other outcomes in real-world heart failure (HF) patients is unclear. This study aimed to evaluate whether ablation reduces death, and other outcomes in real-world AF patients with HF. Among 834,735 patients with AF from 2006 to 2015 in the Korean National Health Insurance Service database, 3173 HF patients underwent AF ablation. Propensity score weighting was used to correct for differences between the groups. During median 54 months follow-up, the risk of all-cause death in ablated patients was less than half of that in patients with medical therapy (2.8 vs. 6.2 per 100 person-years; hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.27–0.65, p < 0.001). Ablation was related with lower risk of cardiovascular death (HR 0.38, 95% CI 0.32–0.62, p < 0.001), HF admission (HR 0.39, 95% CI 0.33–0.46, p < 0.001) and stroke/systemic embolism (HR 0.44, 95% CI 0.37–0.53, p < 0.001). In subgroup analysis, the risk of all-cause death was reduced in most subgroups except in the elderly (≥ 75 years) and strictly anticoagulated patients. Ablation may be associated with reduced risk of all-cause death and cardiovascular death in real-world AF patients with HF, supporting the role of AF ablation in patients with HF.

The Euro Heart Survey and EURObservational Research Programme (EORP) in atrial fibrillation registries: contribution to epidemiology, clinical management and therapy of atrial fibrillation patients over the last 20years.

Management of atrial fibrillation (AF) may be challenging in clinical practice. Given the complexity of AF patients and the continuous advances in AF clinical management, there is a need for standardized programmes aimed at collecting so-called 'real-world clinical practice data' regarding the epidemiology, diagnostic/therapeutic/management practices and assessing adherence to guidelines. Over the past 20years, the number of registries and surveys based on real-world AF patients has been dramatically increased. In Europe, based on the Euro Heart Survey (EHS) and the EURObservational Research Programme (EORP), a large series of studies based on these prospective, observational, large-scale multicentre registries on AF have been published. This narrative review gives an overview of these two projects on AF led by the European Society of Cardiology, focusing mainly on the contribution that these studies have provided to AF management and patient outcomes. Both the EHS and the EORP registries have collected a large amount of data regarding contemporary clinical practice, and despite some limitations, mainly related to their observational nature, these registries have contributed to our knowledge and clinical management of AF patients.

The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients.

To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). Using the Korean National Health Insurance Service database, we identified 96197 patients with non-valvular AF who initiated NOAC or warfarin in 2013-16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC <80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69-0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72-0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91-1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93-1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03-1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.

P4800Estimated effect of NOACs compared to Vitamin K Antagonists in real-world atrial fibrillation patients: Data from FANTASIA Registry

Abstract Background Despite of the effectiveness and safety profile of Non-vitamin K Antagonists Oral Anticoagulants (NOACs) even in real-world (RW) Atrial Fibrillation (AF) patients, Vitamin K Antagonists (VKAs) have remained widely used in clinical practice worldwide but the comparison with acenocoumarol therapy in RW is unknown. Purpose To estimate the potential absolute benefit in clinical adverse events if the AF patients anticoagulated with VKA therapy had been treated with NOACs. Methods We analyzed anticoagulated AF patients who were prospectively recruited into the multicentre FANTASIIA registry. Patients were treated with VKAs for at least 6 months prior to inclusion. The estimation of clinical adverse events avoided was calculated applying absolute risk reductions, relative risk reductions and hazard ratios from the meta-analysis of RW use of NOACs relative to VKAs. Results We analyzed 1,470 patients under VKA therapy (mean age 74.1±9.5 years; 56.4% male). Stroke rate with acenocoumarol treatment was 0.88%/year. The estimated rates for stroke using NOACs would be 0.80%/year for Dabigatran 150 mg; 0.76%/year for Rivaroxaban and 0.74%/year for Apixaban instead of VKA. No significant differences were observed between the different NOACs and VKA in stroke rate. Major bleeding with acenocoumarol was 3.40%/year. The estimated rates for major bleeding using NOACs would be 2.75%/year for Dabigatran 150 mg; 3.37%/year for Rivaroxaban and 2.18%/year for Apixaban instead of VKA. Apixaban was the only NOAC that showed a significant estimated reduction rates (p=0.046). Finally, the all-cause mortality rate with acenocoumarol was 4.69%/year. The estimated rates of all-cause mortality using NOACs would be 3.28%/year for Dabigatran 150mg; 4.88%/year for Rivaroxaban and 2.67%/year for Apixaban. Dabigatran and Apixaban showed significant estimated reduction rates with the highest reduction with Apixaban (Table). Annual Rate reduction of adverse events Conclusion The absolute estimated effect of NOACs in the AF patients anticoagulated with VKA showed a significant reduction in adverse clinical events. Apixaban performed the highest estimated reduction in major bleeding and all-cause mortality in comparison with acenocoumarol.

Consensus Clinical Decision-Making Factors Driving Anticoagulation in Atrial Fibrillation

Guideline-recommended anticoagulation is frequently omitted in high-risk patients with atrial fibrillation (AF) for reasons not fully understood, which may result in suboptimal care. A nationally representative, expert group of physicians (cardiology, neurology, and general medicine), and clinical pharmacists participated in a consensus-seeking, modified Delphi method to identify key clinical decision-making factors driving anticoagulant prescribing in real-world AF patients. Representing >2,500 anticoagulation-related patient encounters per month, 27 of 30 participants completed the study (90% overall response rate). In Round-1, experts rated their level of agreement with factors and suggested modifications or additional factors. Of 66 factors entering Round-1, 21 met and 4 partially met consensus, 41 did not meet consensus, and 7 were newly suggested. Of 32 factors advanced for scoring in Round-2, 16 met consensus criteria. In Round-3, experts were given the option to rescue up to 2 of the 16 nonconsensus factors from Round-2. Including a concomitant need for dual antiplatelet therapy, no factor was successfully rescued into consensus. The most important factors related to risk of infarction rather than bleeding risk or other patient-specific considerations. Among factors not independently addressed in current guidelines, these included baseline hematologic indicators of potential bleeding risk, previous bleeding episodes by specific type, other risk factors for bleeding, and adherence. In conclusion, when determining anticoagulation strategies in AF, there is a need for further research on the clinical implications of these emerging factors as well as the reasons behind divergent opinions toward nonconsensus factors.

Rate and rhythm therapy in patients with atrial fibrillation and the risk of pacing and bradyarrhythmia

Management of atrial fibrillation (AF) with rate and rhythm therapy can cause bradyarrhythmia. To assess overall risk, temporal risk, and subgroup at risk of bradyarrhythmia-related events by rate and/or rhythm therapy drugs. Using Danish nationwide registries, patients with AF between 2000 and 2014 were included if prescribed with rate-lowering drugs (RLDs) or antiarrhythmic drugs (AADs). An adjusted time-dependent Poisson regression model estimated the association between RLDs and AADs with a composite endpoint of pacemaker, temporary pacing, and bradyarrhythmia hospitalization. Secondary outcomes were each individual event. Among 135,017 AF patients, 9196 (6.8%) patients experienced the composite endpoint with a median follow-up of 3.7 (interquartile range [IQR]: 1.6-7.0) years. Median age was 74 (IQR: 65-82) years and 47.6% were women. With rate-lowering monotherapy as the reference, the incidence rate ratios (IRR) (95% confidence interval) for the composite endpoint were 1.36 (1.29-1.43) for rate-lowering dual therapy, 1.62 (1.43-1.84) for antiarrhythmic monotherapy, and 2.49 (2.29-2.71) for AAD combined with RLDs. Similar trend was found for each secondary outcome. Particularly amiodarone increased the risk. This association was strongest within the first 2 weeks of treatment. In those treated with AAD combined with RLDs, high-risk populations were patients ≥70 years (IRR: 3.35 [2.51-4.45] compared to patients <60 years), and women (IRR: 1.35 [1.15-1.57], compared to men). In real-world AF patients, rate-lowering dual therapy, antiarrhythmic monotherapy, and AADs combined with RLDs were positively associated with bradyarrhythmia-related events. The risk was highest in those treated with amiodarone, in the initial 2 weeks of treatment, in women, and in the elderly.

Refining Stroke and Bleeding Prediction in Atrial Fibrillation by Adding Consecutive Biomarkers to Clinical Risk Scores

Background and Purpose- Current European guidelines for the management of atrial fibrillation suggest using biomarkers to refine the risk stratification process. However, it is unclear whether ≥2 biomarkers incrementally improve risk prediction beyond 1 biomarker alone. We investigated whether the predictive performance of CHA2DS2-VASc and HAS-BLED scores could be enhanced by incrementally adding consecutive different biomarkers in real-world atrial fibrillation patients taking vitamin K antagonists therapy. Methods- We included 940 atrial fibrillation patients stable on vitamin K antagonists (international normalized ratio, 2.0-3.0) for at least the previous 6 months. At inclusion, VWF (von Willebrand factor), high-sensitivity troponin T, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity IL (interleukin)-6, fibrin monomers, and BTP (β-trace protein) concentrations were quantified. During follow-up, all adverse events were recorded, and biomarkers were added to CHA2DS2-VASc and HAS-BLED scores depending on the C index. Results- During 6.5 (4.3-7.9) years, there were 98 ischemic strokes (1.60% per year) and 172 major bleeds (1.60% per year). After the addition of biomarkers, the predictive performance of CHA2DS2-VASc was not significantly increased, although the model with 3 biomarkers (ie, NT-proBNP+BTP+VWF) showed a low gain in sensitivity (integrated discrimination improvement, 2.70%; P<0.001). The predictive performance of HAS-BLED was enhanced in all biomarker-based models, with the best prediction shown by the model with 3 biomarkers (ie, VWF+NT-proBNP+high-sensitivity IL-6; C index, 0.600 [95% CI, 0.561-0.625] versus 0.639 [95% CI, 0.607-0.669]; P=0.025). This model also confirmed an increased sensitivity (integrated discrimination improvement, 5.20%; P<0.001) and positive reclassification (net reclassification improvement, 19.20%; P=0.020). Conclusions- By adding consecutive biomarkers, the predictive ability of CHA2DS2-VASc for ischemic stroke was not increased, whereas the predictive ability of HAS-BLED for major bleeding was only slightly enhanced. The net benefit and clinical usefulness of the biomarker-based models were marginal in comparison to the original scores based on clinical factors.

A prospective study of the clinical outcomes and prognosis associated with comorbid COPD in the atrial fibrillation population.

BackgroundPatients with COPD are at higher risk of presenting with atrial fibrillation (AF). Information about clinical outcomes and optimal medical treatment of AF in the setting of COPD remains missing. We aimed to describe the prevalence of COPD in a sizeable cohort of real-world AF patients belonging to the same healthcare area and to examine the relationship between comorbid COPD and AF prognosis.MethodsProspective analysis performed in a specific healthcare area. Data were obtained from several sources within the “data warehouse of the Galician Healthcare Service” using multiple analytical tools. Statistical analyses were completed using SPSS 19 and STATA 14.0.ResultsA total of 7,990 (2.08%) patients with AF were registered throughout 2013 in our healthcare area (n=348,985). Mean age was 76.83±10.51 years and 937 (11.7%) presented with COPD. COPD patients had a higher mean CHA2DS2-VASc (4.21 vs 3.46; P=0.02) and received less beta-blocker and more digoxin therapy than those without COPD. During a mean follow-up of 707±103 days, 1,361 patients (17%) died. All-cause mortality was close to two fold higher in the COPD group (28.3% vs 15.5%; P<0.001). Independent predictive factors for all-cause mortality were age, heart failure, diabetes, previous thromboembolic event, dementia, COPD, and oral anticoagulation (OA). There were nonsignificant differences in thromboembolic events (1.7% vs 1.5%; P=0.7), but the rate of hemorrhagic events was significantly higher in the COPD group (3.3% vs 1.9%; P=0.004). Age, valvular AF, OA, and COPD were independent predictive factors for hemorrhagic events. In COPD patients, age, heart failure, vasculopathy, lack of OA, and lack of beta-blocker use were independent predictive factors for all-cause mortality.ConclusionAF patients with COPD have a higher incidence of adverse events with significantly increased rates of all-cause mortality and hemorrhagic events than AF patients without COPD. However, comorbid COPD was not associated with differences in cardiovascular death or stroke rate. OA and beta-blocker treatment presented a risk reduction in mortality while digoxin use exerted a neutral effect.

P6240Long term cardiovascular risk prediction in Real-World atrial fibrillation patients: Validation of the 2MACE score in the FANTASIIA registry

P6240Long term cardiovascular risk prediction in Real-World atrial fibrillation patients: Validation of the 2MACE score in the FANTASIIA registry

4366Estimated effectiveness and safety of non-vitamin K antagonist oral anticoagulants compared to optimally anticoagulated real-world atrial fibrillation patients taking acenocoumarol

4366Estimated effectiveness and safety of non-vitamin K antagonist oral anticoagulants compared to optimally anticoagulated real-world atrial fibrillation patients taking acenocoumarol

P3579Differences between randomized controlled clinical trials and real-world atrial fibrillation patients treated with oral anticoagulants - do we treat the same patients? Results from the CRAFT study

P3579Differences between randomized controlled clinical trials and real-world atrial fibrillation patients treated with oral anticoagulants - do we treat the same patients? Results from the CRAFT study

P5831Evaluation of ABC-stroke and CHA2DS2-VASc ischemic scores in real-world atrial fibrillation patients receiving oral anticoagulation treatment

P5831Evaluation of ABC-stroke and CHA2DS2-VASc ischemic scores in real-world atrial fibrillation patients receiving oral anticoagulation treatment