Incident Atrial Fibrillation Diagnosis Research Articles

Usefulness of left ventricular mechanical dyssynchrony for predicting atrial fibrillation and adverse outcomes following first atrial fibrillation event

Abstract Background Left ventricular mechanical dyssynchrony (LVMD) has shown to predict many cardiovascular outcomes including ventricular arrhythmias. Our hypothesis is that LVMD can reveal early atrial dysfunction. Purpose The aim of this study was to investigate whether LVMD can be used to predict atrial fibrillation (AF) and adverse outcomes following first AF event in individuals from the general population. Methods A total of 3785 individuals (mean age 55±17 years, 57% women) from the general population free of AF, heart failure (HF) and prior stroke had an echocardiographic examination performed including two-dimensional speckle tracking echocardiography. LVMD was calculated as the standard deviation of the regional time-to-peak strain from the three apical views. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or HF after the diagnosis of AF. Results During a median follow-up of 5 years (interquartile range, 4.4-6.2 years), 142 (4%) individuals were diagnosed with AF, and of these 22 (15%) individuals developed HF or stroke. LVMD was a univariable predictor of AF (per 10ms increase: HR 1.03; 95% CI (1.02-1.05), p<0.001, Figure). The association remained significant even after multivariable adjustment for age, sex, body mass index, diabetes, hypertension, heart rate, previous ischaemic heart disease, systolic blood pressure, diastolic blood pressure, smoking, left ventricular ejection fraction, global longitudinal strain, left atrial volume index (LAVI), and E/e’ (per 10ms increase: HR 1.02; 95% CI (1.00-1.04), p=0.042). LVMD also predicted complicated AF, and the association remained significant even after multivariable adjustment (per 10ms increase: HR 1.05; 95% CI (1.01-1.09), p=0.026). Furthermore, LVMD provided incremental prognostic information over the LAVI with regard to predicting AF (Harrell’s C-statistics 0.66 vs. 0.70, p=0.012). Conclusion In a low-risk general population, LVMD provides prognostic information on the risk of AF. Additionally, LVMD can identify individuals with complicated AF defined as occurrence of either stroke or HF following the diagnosis of incident AF. Furthermore, LVMD provides incremental prognostic information over the LAVI in predicting AF.

Delay and Pay? Healthcare Costs Associated with Late Oral Anti-coagulant Prescribing in People with Atrial Fibrillation.

Atrial fibrillation (AF) is associated with increased morbidity and mortality and exerts an increasingly significant burden on global healthcare resources, with its prevalence rising with an ageing population. Despite a substantial thromboembolic risk, particularly in the period immediately following diagnosis, oral anti-coagulation is frequently not initiated or is delayed. The aim of this study was to evaluate healthcare costs in people with AF, comparing those who were commenced on oral anti-coagulation in the immediate period following the index diagnosis date with those in whom initiation was late and those who never started anti-coagulation. This retrospective cost analysis used linked Scottish health data to identify adults newly diagnosed with AF between January 1st 2012 and April 30th 2019 with a baseline CHA2DS2-VASc score of ≥2. This AF population was sub-divided according to timing of the first prescription of oral anti-coagulant (OAC) during a 2-year follow-up period: never started (OAC never initiated), immediate OAC (OAC prescribed within 60 days of incident AF diagnosis), and delayed OAC (OAC prescribed more than 60 days after incident AF diagnosis). A two-part model was developed, adjusted for key covariates, including age, sex, and frailty, to estimate costs for inpatient admissions, outpatient care, prescriptions, and care home admissions, and overall costs. Of an overall AF population of 54,385, 26,805 (49.3%) never commenced OAC, 7654 (14.1%) initiated an OAC late, and 19,926 (36.6%) were prescribed anti-coagulation immediately. The mean adjusted cost for the overall AF population was £7807 per person per year (unadjusted: £8491). Delayed OAC initiation was associated with the greatest adjusted estimated mean annual cost (unadjusted: £13,983; adjusted: £9763), compared to those that never started (unadjusted: £10,433; adjusted: £7981) and those that received an immediate OAC prescription (unadjusted: £3976; adjusted: £6621). Increasing frailty, mortality, and female sex were associated with greater healthcare costs. AF is associated with significant healthcare resource utilisation and costs, particularly in the context of delayed or non-initiation of anti-coagulation. Indeed, there exists substantial opportunity to improve the utilisation and prompt initiation in people newly diagnosed with AF in Scotland. Interventions to mitigate against the growing economic burden of AF should focus on reducing admissions to hospitals and care homes, which are the principal drivers of costs; prescriptions and outpatient appointments account for a relatively small proportion of overall costs for AF.

Beta-Blockers, Digoxin, or Both Following an Incident Diagnosis of Atrial Fibrillation: A Prospective Cohort Study.

Atrial fibrillation is one of the most common arrhythmias, but the optimal drug choice for a rate control strategy remains uncertain. A retrospective cohort claims database study of patients with an incident hospital discharge diagnosis of atrial fibrillation between 2011 and 2015. The exposure variables were a discharge prescription for beta-blockers, digoxin, or both. The primary outcome was a composite of total in-hospital mortality or a repeat cardiovascular (CV) hospitalization. Baseline confounding was controlled with propensity score inverse probability weighting using a entropy balancing algorithm and the prespecified estimand was the average treatment effect among the treated. Treatment effects for the weighted samples were calculated from a Cox proportional hazards model. A total of 12,723 patients were discharged on beta-blockers alone, 406 on digoxin alone, and 1499 discharged on combined beta-blocker and digoxin therapy with a median follow-up time of 356 days. After baseline covariate adjustment, the digoxin alone (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.85-1.81) and the combined group (HR, 1.09; 95% CI, 0.90-1.31) were not associated with increased risk for the composite endpoint compared with the beta- blocker-alone group. These results were robust to sensitivity analyses. Patients hospitalized for incident atrial fibrillation and discharged on digoxin alone or the combination of digoxin and a beta-blocker were not associated with an increase in the composite outcome of recurrent CV hospitalizations and death compared with those discharged on isolated beta-blocker therapy. However, additional studies are required to refine the precision of these estimates.

Understanding risks and time to congestive heart failure following incident atrial fibrillation

Objectives: Evaluate how different comorbidities increase 3-year risk of incident congestive heart failure (CHF) in new atrial fibrillation (AF) patients and the time from diagnosis of AF to developing incident CHF while controlling for risk factors and treating death as a competing risk event. Methods: We utilized CMS Medicare 100% inpatient and outpatient claims data between 2013 and 2017. Patients with new AF diagnosis (without concurrent CHF at AF diagnosis) in 2014 who had 1-year continuous enrollment prior to their AF diagnosis (baseline period) and no prior diagnosis of AF or CHF in the baseline period were identified. Results: With every 1-year increase in age of incident AF patients, 3-year risk of CHF increases by 2.6%, presence of coronary artery disease, COPD, diabetes mellitus, peripheral artery disease, and cardiomyopathy increases 3-year risk of CHF by 22.1%, 30.2%, 31.9%, 15.2%, 44.8%, and 6.3% respectively. Blacks with incident AF had 6.9% higher 3-year risk CHF than Whites. For the average aged female patient in our cohort (78.5years) with no comorbidities and death as a competing risk, we found the probability of CHF within the first 3 years after AF diagnosis to be 23.5%, 17.5% within the first 2 years, and 10% within the first year. Conclusion: Various comorbidities affect the risk of CHF differently in incident AF patients. Cumulative risk of incident CHF appears to increase fastest within the first few years following incident AF diagnosis.

Healthcare utilization and costs associated with a diagnosis of incident atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most prevalent arrhythmia among adults worldwide and is associated with an increased risk of heart failure, stroke, and death. Prior studies have highlighted the healthcare burden associated with AF; however, contemporary data is lacking. As AF incidence and prevalence continue to increase due to the aging of the population, current estimates are needed for adequate healthcare resource allocation and policy decisions. Purpose The purpose of our study was to examine the healthcare utilization and cost burden associated with a diagnosis of incident AF in the United States (US). Methods Using the 2017–2020 Optum Clinformatics database, an administrative claims data of commercially insured individuals in the US, adult patients with an incident diagnosis of AF were identified. Adults with AF were matched on demographic and comorbid characteristics to those without AF using a propensity score greedy-matching algorithm with a 1:1 case to control ratio. Outcomes including medical services (inpatient admissions, emergency room [ER] visits, outpatients admissions, other services), utilization (all-cause, cardiovascular [CV]-related), and healthcare costs (sum of all medical services and prescription costs; adjusted for medical inflation and reported in 2021 US $) in the one-year post-incident diagnosis of AF were then compared among the matched cohort. Logistic and general linear modeling assessed healthcare utilization and cost outcomes. Results A total of 159,242 matched participants (79,621 AF cases and 79,621 non-AF controls) were identified. Among patients with AF, the mean age was 74 years, and 51% were females. Among the non-AF controls, the mean age was 73 years, and 50% were females. Patients with incident AF had significantly higher all-cause inpatient visits (relative risk [RR] 1.72; 95% confidence interval [CI]: 1.71–1.73), cardiovascular-related inpatient visits (RR 2.42; 95% CI: 2:41–2:44), as well as cardiovascular-related ER visits (RR: 2.36; 95% CI: 2:30–2:42) as compared to non-AF controls in the 1-year following diagnosis (Figure 1). The one-year mean total healthcare costs were $25,006 (95% CI $24,357-$26,912) higher among patients with AF as compared to non-AF controls ($63,031 vs $38,025, p<0.001). Conclusion Patients with AF had significantly higher medical services use than non-AF controls. The higher medical services utilization among the AF cohort translated into a considerably higher economic burden in this cohort. Timely management and treatment remain critical in alleviating the significant financial and health burden imposed by AF on patients, payers, and providers. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Johnson and Johnson

Incidence in atrial fibrillation in Denmark in relation to country of origin: a nationwide register-based study

Abstract Background Immigrants' healthcare needs can be a considerable challenge, as their risk profile can differ from the native population, and they may experience barriers to accessing health services in recipient countries. Immigration is projected to increase further due to conflicts and climate changes, and awareness on immigrants' health status is therefore warranted. Atrial fibrillation (AF) is the most common sustained arrhythmia with an estimated prevalence of approximately 2%. However, there is a paucity of data on AF epidemiology among immigrants. Purpose The aim of this study is to examine incidence of AF hospital diagnoses according to country of origin and to study if there is a difference in risk between immigrants and Danish born individuals. Methods The study period included 1st of January 1998 to 31st of December 2017 and the population consisted of all Danish citizens aged 45 or older. We included individuals as they turned 45 during the study period. Individuals who had been diagnosed with AF were excluded. Data was obtained from the Danish National Patient Registry and the Civil Registration System. Country of origin was based on the ten most represented counties in the population. Immigrants were defined as people born outside Denmark with none of the parents being both Danish citizens and born in Denmark. AF was defined as a hospital diagnosis according to international Classification of Diseases (ICD) version 8 and 10. Poisson regression were used to compute relative risk (RR) and associated 95% confidence intervals (CI). RRs were adjusted for sex, age, socioeconomic status, visits to general practitioner and comorbidity. Results The study population consist of 3,596,234 Danish-Born and 215,401 immigrants. A total of 334,636 had an incident AF diagnosis during the study period. Compared to Danish-born individuals, migrants from the Nordic countries had a higher adjusted RR of being diagnosed with AF: Norway 1.21 [95% CI: 1.05; 1.40], Sweden 1.16 [95% CI: 0.99; 1.35] and Germany 1.17 [95% CI: 1.06; 1.28]. In contrast, lower adjusted RRs were observed for individuals from Poland (0.82 [95% CI: 0.67; 1.01]), UK (0.89 [95% CI: 0.73; 1.08]), and the US (0.95 [95% CI: 0.72; 1.25]), respectively, and in particular for individuals from the non-Western countries: Turkey (0.49 [95% CI: 0.40; 0.59], Iran (0.48 [95% CI: 0.36; 0.65]), Iraq (0.32 [95% CI: 0.22; 0.45] and Bosnia-Herzegovina (0.63 [95% CI: 0.49; 0.79]). Conclusion Substantial variation in the incidence rate of incident AF hospital diagnoses according to country of origin. Further studies are warranted in order to clarify to what extent these differences reflets true differences in AF incidence or ethnic inequalities in the detection of AF in the health care system. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Karen Elise Jensen Foundation

Healthcare utilization and costs associated with a diagnosis of incident atrial fibrillation.

Atrial fibrillation (AF) is the most common heart rhythm disorder among adults and leads to substantial morbidity and mortality. The purpose of the study was to provide current estimates on the incremental healthcare utilization and cost burden associated with incident AF diagnosis in the United States. Adults with an incident diagnosis of AF (2017-2020) were identified using the Optum Clinformatics database. Propensity matching was employed to match patients with incident AF to a comparator group of non-AF patients on several demographic and clinical characteristics. Outcomes including 12-month all-cause and cardiovascular (CV)-related healthcare utilization, as well as the medical cost associated with health services use, were assessed. Logistic and general linear models were used to examine study outcomes. Sub-analyses were performed to determine the incremental AF burden by specific sex and racial/ethnic categories. A total of 79,621 patients were identified in each cohort (AF and non-AF). As compared to the non-AF cohort, patients with AF had significantly higher all-cause inpatient visits (relative risk [RR] 1.77; 95% confidence interval [CI] 1.76-1.78), CV-related inpatient visits (RR 2.51; 95% CI 2:49-2:53), and CV-related emergency room visits (RR: 2.41; 95% CI 2:35-2:47). The mean total healthcare cost for patients with AF was $27,896 more (per patient per year) than the non-AF cohort ($63,031 vs $35,135, P < .001). Medical services utilization and cost were significantly higher among AF patients than non-AF patients. Early treatment is likely to be critical to addressing the considerable disease burden imposed by AF.

Formulary restrictions and stroke risk inpatients with atrial fibrillation.

To determine the use of formulary restrictions (prior authorization and step therapy) on the use of non-vitamin K antagonist oral anticoagulants (NOACs) and their effect on health outcomes. Longitudinal cohort study. We identified a sample of Medicare beneficiaries with an incident diagnosis of atrial fibrillation (AF) in 2011 to 2015 and followed them until the end of 2016 or death. We compared anticoagulant use and health outcomes associated with Medicare Part D plan coverage of NOACs. The primary outcomes were composite rates of death, stroke, transient ischemic attack, and systemic embolism. We used Cox proportional hazards models to estimate the association between formulary restrictions and adverse health outcomes. Beneficiaries enrolled in Part D plans that restricted access to NOACs had a lower probability of NOAC use (30.2% vs 32.2%), worse adherence conditional on NOAC use (32.1% vs 34.3% adherent), and longer delays in filling an initial prescription (46% vs 55% filled within 30 days of AF diagnosis). Beneficiaries in restricted plans had higher aggregate risk of mortality/stroke/transient ischemic attack (adjusted HR, 1.098; 95% CI, 1.079-1.118). Limiting access to NOACs may exacerbate current underuse of anticoagulants and increase the risk of stroke among patients with newly diagnosed AF. Pharmacy benefit managers and Part D plans need to continuously review the appropriateness of formulary policies to ensure patient access to effective medications.

Social determinants of health and catheter ablation after an incident diagnosis of atrial fibrillation: a Danish nationwide cohort study.

To examine (i) the sex-specific associations between three social determinants of health (SDOH) and use of ablation after incident atrial fibrillation (AF), and (ii) the temporal trends in these associations. We conducted a nationwide cohort study of patients with an incident hospital diagnosis of AF between 2005 and 2018. SDOH at the time of AF diagnosis included three levels of educational attainment, tertile groups of family income, and whether the patient was living alone. Outcome was catheter ablation for AF. We used cause-specific proportional hazard models to estimate hazard ratios (HR) with 95% CI and adjusted for age. To examine temporal trends, we included an interaction term between the exposure and calendar years. Among 122276 men, those with lower education [HR 0.49 (95%CI 0.45-0.53)] and 0.72 (0.68-0.77) for lower and medium vs. higher], lower income [HR 0.31 (0.27-0.34) and 0.56 (0.52-0.60) for lower and medium vs. higher], and who lived alone [HR 0.60 (0.55-0.64)] were less likely to receive AF ablation. Among 98476 women, those with lower education [HR 0.45 (0.40-0.50) and 0.83 (0.75-0.91) for lower and medium vs. higher], lower income [HR 0.34 (0.28-0.40) and 0.51 (0.46-0.58) for lower and medium vs. higher], and who lived alone [HR 0.67 (0.61-0.74)] were less likely to receive AF ablation. We found no evidence of temporal trends in the associations. In the Danish universal healthcare system, patients with AF who had lower educational attainment, lower family income, or were living alone were less likely to undergo AF ablation.

Thromboembolic Risk in Patients With Pneumonia and New-Onset Atrial Fibrillation Not Receiving Anticoagulation Therapy

New-onset atrial fibrillation (AF) is commonly reported in patients with severe infections. However, the absolute risk of thromboembolic events without anticoagulation remains unknown. To investigate the thromboembolic risks associated with AF in patients with pneumonia, assess the risk of recurrent AF, and examine the association of initiation of anticoagulation therapy with new-onset AF. This population-based cohort study used linked Danish nationwide registries. Participants included patients hospitalized with incident community-acquired pneumonia in Denmark from 1998 to 2018. Statistical analysis was performed from August 15, 2021, to March 12, 2022. New-onset AF. Thromboembolic events, recurrent AF, and all-cause death. Estimated risks were calculated for thromboembolism without anticoagulation therapy, new hospital or outpatient clinic contact with AF, initiation of anticoagulation therapy, and all-cause death at 1 and 3 years of follow-up. Death was treated as a competing risk, and inverse probability of censoring weights was used to account for patient censoring if they initiated anticoagulation therapy conditioned on AF. Among 274 196 patients hospitalized for community-acquired pneumonia, 6553 patients (mean age [SD], 79.1 [11.0] years; 3405 women [52.0%]) developed new-onset AF. The 1-year risk of thromboembolism was 0.8% (95% CI, 0.8%-0.8%) in patients without AF vs 2.1% (95% CI, 1.8%-2.5%) in patients with new-onset AF without anticoagulation; this risk was 1.4% (95% CI, 1.0%-2.0%) among patients with AF with intermediate stroke risk and 2.8% (95% CI, 2.3%-3.4%) in patients with AF with high stroke risk. Three-year risks were 3.5% (95% CI, 2.8%-4.3%) among patients with intermediate stroke risk and 5.3% (95% CI, 4.4%-6.5%) among patients with high stroke risk. Among patients with new-onset AF, 32.9% (95% CI, 31.8%-34.1%) had a new hospital contact with AF, and 14.0% (95% CI, 13.2%-14.9%) initiated anticoagulation therapy during the 3 years after incident AF diagnosis. At 3 years, the all-cause mortality rate was 25.7% (95% CI, 25.6%-25.9%) in patients with pneumonia without AF vs 49.8% (95% CI, 48.6%-51.1%) in patients with new-onset AF. This cohort study found that new-onset AF after community-acquired pneumonia was associated with an increased risk of thromboembolism, which may warrant anticoagulation therapy. Approximately one-third of patients had a new hospital or outpatient clinic contact for AF during the 3-year follow-up, suggesting that AF triggered by acute infections is not a transient, self-terminating condition that reverses with resolution of the infection.

Changes in antithrombotic treatment in patients with abdominal aortic aneurysmal disease and incident atrial fibrillation: a population-based case-crossover analyses

Abstract Background Abdominal aortic aneurysmal (AAA) disease is associated with a high risk of cardiovascular events, and prophylaxis with platelet-inhibitors are recommended at diagnosis. Incident atrial fibrillation (AF) changes that indication to oral anticoagulative (OAC) therapy. However, it is unknown to what extent the recommended change of indication is reflected in the actual antithrombotic treatment in clinical practice. Purpose To evaluate the antithrombotic therapy after an incident diagnosis of atrial fibrillation in patients with established AAA. Methods In this population-based case-crossover study, using nationwide Danish registries, we identified all patients registered with a diagnosis of AAA between 1997 and 2018, and a subsequent diagnosis of AF. The case-crossover analysis was performed to compare the within-subject antithrombotic therapy in 1-year time-periods before and after AF diagnosis in the study population. A blanking period of 30 days before AF-diagnosis was applied to avoid bias from potentially delayed hospital diagnosis of AF (Figure 1.1). We excluded patients with no eligible reference window due to recent cohort entry and patients with no AF-related indication for shift to OAC (CHA2DS2-VASc score of &amp;lt;1 in men and &amp;lt;2 in women). Odds ratios (OR) with 95% confidence intervals (CIs) comparing antithrombotic therapy before and after AF diagnosis was calculated using McNemars test for matched pair's data. Subgroup analyses of patients diagnosed with AAA between 2011 and 2018 were performed to evaluate changes after introduction of current antithrombotic treatment regimens and direct oral anticoagulants. Results A total of 3052 patients were included in the case-crossover analyses. Mean age was 77.8 years and 22.3% were females. Median time from AAA to AF diagnosis was 4.6 years (IQR; 2.6–7.8). Stroke risk in the study population was high with a median CHA2DS2-VASc score of 4 (IQR: 3–5). In the case-period after AF diagnosis, 1004 prescription claims of platelet-inhibitors were registered compared with 1461 claims in the control-period before AF diagnosis, corresponding to a matched OR of 0.31 (95% CI, 0.26–0.36) (Figure 1.2). Conversely, there were 1392 prescription claims for OAC in the case-period compared with 355 in the control-period, corresponding to an OR of 15.75 (95% CI, 12.38–20.31). When restricting the study-population to patients diagnosed with AAA during 2011–2018, the OR was 0.11 (95% CI, 0.07–0.16) for a prescription claim of platelet-inhibitors and 17.7 (95% CI, 11.22–29.17) for OAC before and after AF diagnosis (Figure 1.2). Conclusion In patients with established AAA and high risk of stroke, incident AF was associated with low likelihood of treatment with platelet-inhibitor and a high likelihood of OAC-treatment compared with before AF. This association was further strengthened in patients diagnosed after 2011. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Obel Family Foundation, DenmarkThe Augustinus Foundation, DenmarkThe sponsors played no role in the study design; data collection, analysis, or interpretation; abstract writing; or in the decision to submit the abstract. Figure 1

Socioeconomic trends in oral anticoagulation therapy for atrial fibrillation patients with low risk of stroke

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Karen Elise Jensen Foundation Obel Family Foundation Background Studies suggest that oral anticoagulation (OAC) drugs are underused in patients with atrial fibrillation (AF) and high risk of stroke, especially in patients with low socioeconomic position (SEP). It is unknown, however, if the socioeconomic differences in guideline recommended practice exists in patients with low risk of stroke where OAC is not indicated. Purpose To examine the association between educational status and OAC treatment in patients with low risk of stroke where OAC was not indicated. Methods Register-based study. We included all Danish patients with a hospital diagnosis of incident AF between 1 Maj 1999 and 2 October 2015 with low risk of stroke according to guidelines covering the specific year of inclusion. Educational level was used as indicator for SEP. Outcome was OAC initiation -30 or +90 days of incident AF. Generalized linear regression was used to estimate absolute risk differences (RDs) between educational groups. Results 33805 AF patients with low risk of stroke were included (74.2 % men, mean age 56.4 years). Figure 1 shows that OAC was widely used in low-risk AF patients, especially in men. The initiation of OAC increased with time but the educational differences were reduced for women. Risk difference in the 1999-2002 was -14 % for women with high education (reference: low education) and -2 % in the period 2013-2016. Conclusion OAC was overused in patients with low risk of stroke, especially in patients with low education and the overuse increased with time. Educational differences were, however, slightly reduced with time, especially for women. Initiatives to ensure adherence to guideline recommendations should be emphasized in AF patients with low risk of stroke, especially for men and patients with low education. Figure 1. Percentages per year for initiation of OAC according to educational status. Abstract Figure.

Risk of Incident Atrial Fibrillation With Zoledronic Acid Versus Denosumab: A Propensity Score-Matched Cohort Study.

Zoledronic acid (ZA) is an effective agent in osteoporosis and malignancy-related bone disease but may be associated with increased risk of atrial fibrillation (AF), although current studies disagree on this risk. To examine the risk of incident AF among patients receiving ZA compared with denosumab in the first year of treatment, we performed a new-user, active comparator cohort study including privately insured Americans between January 1, 2010, and June 30, 2019. Individuals aged ≥50 years without known arrhythmia or advanced kidney disease who initiated ZA were 1:1 propensity score (PS)-matched to individuals initiating denosumab in separate osteoporosis and malignancy cohorts. The primary outcome was incident diagnosis of AF (≥1 inpatient or ≥2 outpatient diagnostic codes) over 1 year. Secondary outcomes included stroke/transient ischemic attack (TIA) and nonvertebral fracture. In the osteoporosis cohort (n = 16,235 pairs), mean age was 71 years, and 93% were female. There was higher risk of AF with ZA compared with denosumab over 1 year (incidence rate [IR] = 18.6 versus 14.9 per 1000 person-years; hazard ratio [HR] = 1.25; 95% confidence interval [CI] 1.04 to 1.50). In the malignancy cohort (n = 7732 pairs), mean age was 70 years, and 66% were female. There was a numerically higher, albeit not statistically significant, risk of AF with ZA compared with denosumab over 1 year (IR = 46.9 versus 39.0 per 1000 person-years; HR = 1.19; 95% CI 1.00 to 1.43; p = 0.06). No difference in stroke/TIA rates occurred. In the malignancy cohort, ZA was less effective than denosumab at preventing nonvertebral fractures (HR = 1.32; 95% CI 1.01 to 1.74). Compared with denosumab, ZA treatment for osteoporosis and possibly for malignancy-related bone disease is associated with modestly increased risk of incident AF in the first year of treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).

Clinical Outcomes of Warfarin Initiation in Advanced Chronic Kidney Disease Patients With Incident Atrial Fibrillation.

The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis. The clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown. In this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA-related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event-related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities. The mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA2DS2-VASc score was 5.7 ± 2.1. Of the overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow-up period. The hazard ratios (95% confidence intervals) for ischemic CVA, bleeding events, and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97), respectively, compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic CVA and bleeding event-related hospitalizations. In patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

Glycemic Status and Thromboembolic Risk in Patients With Atrial Fibrillation and Type 2 Diabetes Mellitus: A Danish Cohort Study.

Background Diabetes mellitus is associated with increased risk of stroke in patients with atrial fibrillation, and differences in glycemic status may affect this risk. We aimed to examine the effect of glycemic status evaluated by hemoglobin A1c (HbA1c) on the risk of thromboembolism among patients with atrial fibrillation and type 2 diabetes mellitus. Methods In this cohort study, we used data from Danish registries to identify patients with type 2 diabetes mellitus and incident nonvalvular atrial fibrillation in the period of May 1, 2005, through December 31, 2015. On the basis of the most recent HbA1c measurement before an incident atrial fibrillation diagnosis, patients were divided into the categories: HbA1c ≤48 mmol/mol, HbA1c=49-58 mmol/mol, and HbA1c >58 mmol/mol. Cox regression analysis was used to estimate hazard ratios for the outcome thromboembolism. Results The study population included 5386 patients with incident nonvalvular atrial fibrillation and type 2 diabetes mellitus. Compared with patients with HbA1c ≤48 mmol/mol, we observed a higher risk of thromboembolism among patients with HbA1c=49-58 mmol/mol (hazard ratio, 1.49; 95% CI, 1.09-2.05) and HbA1c >58 mmol/mol (hazard ratio, 1.59; 95% CI, 1.13-2.22) after adjusting for confounding factors. When stratified on diabetes mellitus duration, similar results were found among patients with diabetes mellitus duration of <10 years. Contrastingly, in patients with diabetes mellitus duration of ≥10 years, higher HbA1c levels were not associated with a higher risk of thromboembolism. Conclusions In patients with incident atrial fibrillation and type 2 diabetes mellitus, increasing levels of HbA1c were associated with a higher risk of thromboembolism. However, no association was found among patients with diabetes mellitus duration ≥10 years.

Incident Atrial Fibrillation, Dementia and the Role of Anticoagulation: A Population-Based Cohort Study.

Atrial fibrillation (AF) is associated with dementia. Anticoagulation may modify this relationship, but it is unclear if this is due to stroke reduction alone. Age- and sex-matched individuals from the U.K. Clinical Practice Research Datalink (2008-2016) with and without an incident diagnosis of AF were followed for a new dementia diagnosis. We estimated adjusted hazard ratios (aHRs) for incident dementia diagnosis in the AF cohort, overall and stratified by anticoagulation status, using the matched non-AF cohorts as reference. We performed a sensitivity analysis excluding individuals with stroke/transient ischaemic attack (TIA) before the observation period. Over 193,082 person-years (mean follow-up 25.7 ± 0.1 months), 347/15,276 AF (2.3%) and 1,085/76,096 non-AF (1.4%) were newly diagnosed with dementia (aHR, 1.31, 95% confidence interval, 1.15-1.49). The AF group had more co-morbidity and higher rates of dementia, both with and without anticoagulation, than non-AF. When those with history of stroke/ TIA before the observation period were excluded and those with incident stroke/TIA during the observation period were censored, AF individuals not on anticoagulation had significantly higher rates of dementia compared with non-AF, aHR 1.30 (1.06-1.58). Our findings support the hypothesis that AF is a distinct risk factor for dementia, independent of stroke/TIA and other vascular risk factors. In those without stroke/TIA, risk of dementia is increased only in those who are not on anticoagulation, suggesting anticoagulation is protective presumably through reduction of sub-clinical embolic events. Further prospective research is needed to better ascertain the role of anticoagulation amongst targeted therapeutic strategies to reduce cognitive decline in AF.

Type 1 versus type 2 diabetes and thromboembolic risk in patients with atrial fibrillation: A Danish nationwide cohort study

BackgroundAtrial fibrillation is a common cause of stroke, and diabetes increases stroke risk. Stroke risk may vary depending on the type of diabetes. We investigated whether type 1 and type 2 diabetes are associated with different risks of thromboembolism among patients with atrial fibrillation. MethodsWe used data from Danish nationwide registries to identify patients with a prior diagnosis of diabetes and an incident nonvalvular atrial fibrillation diagnosis in the period of January 1, 2005 to December 31, 2015. Cox regression analysis was used to estimate hazard ratios (HR) for the outcome thromboembolism. ResultsThe study population included 10,058 patients with a prior diagnosis of diabetes and an incident diagnosis of atrial fibrillation. At three-year follow-up, type 2 diabetes was not associated with a higher risk of thromboembolism compared to type 1 diabetes, with an adjusted HR of 1.15 (95% CI: 0.91–1.44). In an age-stratified analysis, patients aged below 65 years of age had an adjusted HR of 1.97 (95% CI: 1.07–3.61), whereas patients aged 65–74 years or ≥75 years had adjusted HRs of 0.99 (95% CI: 0.67–1.46) and 1.10 (95% CI: 0.80–1.51), respectively. ConclusionWe found no overall credible association between the type of diabetes and risk of thromboembolism in this cohort of non-anticoagulated patients with incident atrial fibrillation. Nonetheless, the subset of patients aged below 65 years of age displayed a higher risk of thromboembolism among patients with type 2 diabetes as compared to patients with type 1 diabetes.

Race and stroke in an atrial fibrillation inception cohort: Findings from the Penn Atrial Fibrillation Free study

Stroke may be the initial manifestation of atrial fibrillation (AF). Limited studies, however, have evaluated racial differences in stroke before the diagnosis of AF. We assessed racial differences in strokes that occurred before and after AF diagnosis in the Penn Atrial Fibrillation Free study. The Penn Atrial Fibrillation Free study consists of 56,835 patients from the University of Pennsylvania Health System who were free of AF at the index visit. We developed an inception cohort of 3507 patients with incident AF and without any remote history of stroke. Among the AF inception cohort, there were 538 patients with ischemic strokes and 54 with hemorrhagic strokes. Nearly half (n = 254; 47%) of the ischemic strokes occurred within a 6-month period before the diagnosis of AF. Of these, the majority of strokes occurred either on the day of (n = 158) or within a 7-day period before (n = 30) the diagnosis of incident AF. The remaining 284 (53%) ischemic strokes occurred a median of 3.6 years (interquartile range 1.9-5.4 years) after AF diagnosis. Compared with whites, blacks had an independently higher risk of having an ischemic stroke either before (adjusted odds ratio 1.37; 95% confidence interval 1.03-1.81) or after (adjusted hazard ratio 1.67; 95% confidence interval 1.30-2.14) AF diagnosis. In the population with incident AF, nearly half of the ischemic strokes occurred before the diagnosis of AF. Compared with whites, blacks had a higher risk of developing an ischemic stroke that persisted whether the stroke occurred in the period either before or after AF diagnosis.

Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA2DS2-VASc score, age and sex - A Swedish nationwide observational study with 48 433 patients.

AimsThere is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA2DS2-VASc score of 1 point.MethodsIn a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA2DS2-VASc score of 0, 1, 2 and ≥3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009.ResultsPatients with 1 point from the CHA2DS2-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65–74 years 0.46 (0.25–0.83), men <65 years 1.11 (0.56–2.23) and women <65 years 2.13 (0.94–4.82), where HR <1 indicates protection with warfarin. In patients <65 years and 2 points, HR in men was 0.35 (0.18–0.69) and in women 1.84 (0.86–3.94) while, in women with at least 3 points, HR was 0.31 (0.16–0.59). In patients 65–74 years and 2 points, HR in men was 0.37 (0.23–0.59) and in women 0.39 (0.21–0.73). Categories including age ≥65 years or ≥3 points showed a statistically significant protection from warfarin.ConclusionsOur results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA2DS2-VASc score is 1.