Singer, Daniel E.

AbstractBackgroundAn unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs).HypothesisAn externally validated model improves ICH risk stratification.MethodsIndependent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD‐AF (Global Anticoagulant Registry in the FIELD‐Atrial Fibrillation) and ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register.ResultsIn the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2‐year period (0.31 per 100 person‐years; 95% confidence interval [CI]: 0.28–0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate‐to‐severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non‐VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25–2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism‐corrected C‐statistic: 0.68; 95% CI: 0.65–0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets.ConclusionsAge, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Atrial fibrillation (AF) is one of the strongest risk factors for ischemic stroke, which is a leading cause of disability and death. Given the aging population, increasing prevalence of AF risk factors, and improved survival in those with cardiovascular disease, the number of individuals affected by AF will continue increasing over time. While multiple proven stroke prevention therapies exist, important questions remain about the optimal approach to stroke prevention at the population and individual patient levels. Our report summarizes the National Heart, Lung, and Blood Institute virtual workshop focused on identifying key research opportunities related to stroke prevention in AF. The workshop reviewed major knowledge gaps and identified targeted research opportunities to advance stroke prevention in AF in the following areas: (1) improving risk stratification tools for stroke and intracranial hemorrhage; (2) addressing challenges with oral anticoagulants; and (3) delineating the optimal roles of percutaneous left atrial appendage occlusion and surgical left atrial appendage closure/excision. This report aims to promote innovative, impactful research that will lead to more personalized, effective use of stroke prevention strategies in people with AF.

Background. Oral anticoagulation therapy (OAC) reduces the risk of thromboembolic events associated with atrial fibrillation (AF), yet a substantial proportion of patients with AF are not prescribed OAC. The frequencies of and factors associated with contraindications to OAC therapy in clinical practice are not well-described. Methods. We used data from the ORBIT-AF study, a national, prospective, outpatient registry of incident and prevalent AF. OAC contraindications were uniformly collected at study enrollment by site personnel. Patient and provider characteristics were compared between participants with documented OAC contraindications at baseline and those without OAC contraindications. Results. From June 2010 to August 2011, 10124 patients ≥18 years old with electrocardiographically documented AF were enrolled at 176 practices. Of these, 1409 (13.9%) had OAC contraindications documented at the baseline visit: prior bleed (26.2%), patient refusal/preference (26.0%), high bleeding risk (22.6%), frequent falls/frailty (16.6%), other (11.9%), need for dual antiplatelet therapy (9.8%), unable to adhere/monitor warfarin (5.7%), comorbid illness (5.0%), prior intracranial hemorrhage (4.7%), allergy (2.3%), occupational risk (0.8%), and pregnancy (0.2%). Compared to patients without contraindications, those with contraindications had higher stroke risk (CHADS2>2) and were older, more likely to be female, more likely to be seen by a cardiologist and less likely to be seen by an electrophysiologist (Table 1). Among those patients with reported contraindications, 28.4% were taking warfarin. Conclusions. Contraindications to OAC therapy among AF patients are common and often due to high bleeding risk. Furthermore, many patients with reported contraindications are taking warfarin, suggesting that many contraindications to warfarin therapy are minor, relative, or temporary.

Objective: Time in the therapeutic range (TTR) of INR 2.0-3.0 is an important measurement of warfarin anticoagulation quality. There are few reports on TTR in United States (US) clinical practice. Methods: Using the US ORBIT AF registry, we analyzed TTR for patients on warfarin with at least 5 recorded INR measurements. The Rosendaal method of linear interpolation was used between each pair of measured INR values. Patients were stratified into quartiles based on TTR. Results: We studied 5,451 patients treated at 169 US sites with 48% of patients being followed at an anticoagulation clinic. Patients had a median age of 76 years [interquartile range (IQR) 68-82 years] and median follow-up was 18.9 months [IQR 12.7-23.3 months], and patients were 42% women. The median number of INR draws was 21 [IQR 12-30]. Patients had an overall median TTR of 68% [IQR 52-80%]. The median TTR by quartile was 40%, 60%, 73%, and 87%. Patients were more likely to be subtherapeutic (median time of 17%) than supratherapeutic (median time of 10%). Patients age 61-80 years and those with a college education had the highest TTRs. Patients with their INR followed at an anticoagulation clinic were more likely to be in the highest TTR quartile than in the lowest (27% vs 23%, p=0.0002). Patients with worsening renal function and higher risk for bleeding (ATRIA) or stroke (CHADS2 score) had lower TTR (p<0.0001 for all) (Figure). Conclusions: In US clinical practices, warfarin patients have therapeutic INR levels about 2/3 of the time. Those at highest risk for stroke and bleeding paradoxically were the least likely to be in the therapeutic range.

Objective: Diabetes is a common among patients with atrial fibrillation (AF). However, little is known on the impact of diabetes on symptoms, health status, care and outcomes among AF patients. We assessed whether symptoms, health status, care and outcomes differ between AF patients with and without diabetes. Methods: This observational cohort study included 9,749 patients with AF from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registry, a prospective, nationwide, multicenter outpatient registry of patients with incident and prevalent AF enrolled at 174 sites between June 2010 and August 2011. The outcomes were symptoms, health status, and AF treatment, as well as 2-year risks of death, readmission, thrombomebolic events, heart failure (HF) and AF progression. Results: Among AF patients; those with diabetes (29.5%) were younger and more likely to have hypertension, chronic kidney disease, HF, coronary heart disease, and stroke. Patients with diabetes had a lower Atrial Fibrillation Effects on Quality of Life score (80.6 [IQR: 62.5 - 92.6] vs. 82.4 [IQR: 67.6 -93.5]; P = 0.025), but a higher CHA 2 DS 2 -VASc score (5 [IQR: 4 - 6] vs. 4 [2 - 5]; P <0.0001) and were more likely to receive anticoagulation ( P <0.001). Diabetes was associated with higher mortality, with a greater overall (adjusted hazard ratio [aHR]: 1.63 [95% CI: 1.04-2.56] for age<70 vs. 1.25 [1.09-1.44] for age ≥70) and cardiovascular (2.20 [1.22-3.98] for age<70 vs. 1.24 [1.02-1.51] for age ≥70) mortality risks before age 70 years. Diabetes conferred a higher risk of non-cardiovascular (CV) death (1.29 [1.06-1.56]), sudden cardiac death (1.53 [1.04-2.26]), hospitalization (1.15 [1.09-1.22]), CV hospitalization (1.13 [1.05-1.22]) and non-CV and non-bleeding-related hospitalization (1.19 [1.10-1.30]); but no increase in risks of thromboembolic events, bleeding related hospitalization, new-onset HF, and AF progression. The use of oral anticoagulants (OAC) modifies the relation of diabetes and all-cause hospitalization, with a higher risk among those on OAC (1.21 [1.12-1.29]). Conclusions: Among patients with AF, diabetes was associated with worse AF symptoms and lower quality of life, as well an increased risk of death and hospitalizations, but not with the risk of thromboembolic or bleeding events.

Introduction: Patient understanding of available therapies for atrial fibrillation (AF) is foundational to shared medical decision making and long term medication adherence. Yet, there is a paucity of data regarding the extent to which patients newly diagnosed with AF in routine community practice understand their options. Hypotheses: 1) Understanding of warfarin, novel oral anticoagulants (NOAC), rhythm control therapy, cardioversion and radio frequency ablation changes little from baseline to 6 months and 2) treatment rates at 6 months are associated with patient understanding of therapies at baseline. Methods: We analyzed survey data from SATELLITE, a substudy of new-onset AF patients enrolled at 56 US sites participating in the ORBIT-AF registry. Patients were surveyed at the baseline and 6 month follow up clinic visit using Likert scales. Agreement between time points was assessed with the McNemar test, and the relationship between understanding and treatment was assessed only for the subset not on treatment at baseline. Results: Of 1000 patients enrolled in SATELLITE, 506 had 6-month survey data (data collection is continuing). Among these, the median age was 69.0 years (IQR 63.0 - 76.0) and 93.7% (474 of 506) were white. There was evidence of improvement in the self-reported understanding of warfarin and NOACs from baseline to 6 months, but not for rhythm control, ablation or cardioversion. The proportion reporting high understanding improved significantly for warfarin (p<.0001) and NOACs (p<.0001) from 47% (223 of 474) and 51% (245 of 481) at baseline to 60% (284 of 474) and 69% (332 of 481) at 6 months respectively (Figure 1). Patients with high understanding of the benefits of ablation (p=0.0005) and options for ablation (p=0.0093) at baseline were more likely to have this therapy at the 6 month follow up (N=590), but improved understanding was not associated with increased use of warfarin/NOACs (N=83) or rhythm control (N=444). Conclusions: Patients with new-onset AF had improved self-reported understanding of some treatment options over the first 6-months from diagnosis; however, factors other than patient understanding may influence AF treatments received at 6 months. Patient understanding of AF treatments remains suboptimal at 6 months, and our results suggest a need for ongoing patient education.

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute’s virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.

Background Cardioversion is common among patients with atrial fibrillation (AF). We hypothesised that novel oral anticoagulants (NOAC) used in clinical practice resulted in similar rates of stroke compared with vitamin K antagonists (VKA) for cardioversion. Methods Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, patients with AF who had a cardioversion, follow-up data and an AF diagnosis within 6 months of enrolment were identified retrospectively. Clinical outcomes were compared for patients receiving a NOAC or VKA for 1 year following cardioversion. Results Among 13 004 patients with AF, 2260 (17%) underwent cardioversion. 1613 met the inclusion criteria for this analysis. At the time of cardioversion, 283 (17.5%) were receiving a VKA and 1330 (82.5%) a NOAC. A transoesophageal echocardiogram (TOE) was performed in 403 (25%) cardioversions. The incidence of stroke/transient ischaemic attack (TIA) at 30 days was the same for patients having (3.04 per 100 patient-years) or not having (3.04 per 100 patient-years) a TOE (p=0.99). There were no differences in the incidence of death (HR 1.19, 95% CI 0.62 to 2.28, p=0.61), cardiovascular hospitalisation (HR 1.02, 95% CI 0.76 to 1.35, p=0.91), stroke/TIA (HR 1.18, 95% CI 0.30 to 4.74, p=0.81) or bleeding-related hospitalisation (HR 1.29, 95% CI 0.66 to 2.52, p=0.45) at 1 year for patients treated with either a NOAC or VKA. Conclusions Cardioversion was a low-risk procedure for patients treated with NOAC, and there were statistically similar rates of stroke/TIA 30 days after cardioversion as for patients treated with VKA. There were no statically significant differences in death, stroke/TIA or major bleeding at 1 year among patients treated with NOAC compared with VKA after cardioversion.

Background: Patients with atrial fibrillation on oral anticoagulation (OAC) undergoing cardiac catheterization face risks for embolic and bleeding events, yet information on strategies to mitigate these risks in contemporary practice is lacking. Methods: We aimed to describe the clinical/procedural characteristics of a contemporary cohort of patients with atrial fibrillation on OAC who underwent cardiac catheterization. Use of bleeding avoidance strategies and bridging therapy were described and outcomes including death, stroke, and major bleeding at 30 days and 1 year were compared by OAC type. Results: Of 13 404 patients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II Registry from 2013 to 2016, 741 underwent cardiac catheterization (139 with percutaneous coronary intervention) in the setting of OAC. The patients’ median age was 71, 61.8% were male, white (87.2%), had hypertension (83.7%), hyperlipidemia (72.1%), diabetes mellitus (31.6%), and chronic kidney disease (28.2%); 20.2% received warfarin while 79.8% received direct acting oral anticoagulant. One third of patients underwent radial artery access, and bivalirudin was used in 4.6%. Bridging therapy was used more often in patients on warfarin versus direct acting oral anticoagulant (16.7% versus10.0%). OAC was interrupted in 93.8% of patients. Patients on warfarin versus direct acting oral anticoagulant were equally likely to restart OAC (58.0% versus 60.7%), had similar use of antiplatelet therapy (44.0% versus 41.3%) after catheterization, and had similar rates of myocardial infarction and death at 1 year, but higher rates of major bleeding (43.3 versus 12.9 events/100 patient years) and stroke (4.9 versus 1.9 events/100 patient years). Conclusions: In a real-world registry of patients with atrial fibrillation undergoing cardiac catheterization, most cases are elective, performed by femoral access, with interruption of OAC. Bleeding avoidance strategies such as radial artery access and bivalirudin were used infrequently and use of bridging therapy was uncommon. Nearly 40% of patients did not restart OAC postprocedure, exposing patients to risk for stroke. Further research is necessary to optimize the management of patients with atrial fibrillation undergoing cardiac catheterization.

Abstract Aims To determine the extent of shared decision-making (SDM), during selection of oral anticoagulant (OAC) and rhythm control treatments, in patients with newly diagnosed atrial fibrillation (AF). Methods and results We evaluated survey data from 1006 patients with new-onset AF enrolled at 56 US sites participating in the SATELLITE substudy of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT II). Patients completed surveys at enrolment and at 6-month follow-up. Patients were asked about who made their AF treatment decisions. Shared decision-making was classified as one that the patient felt was an autonomous decision or a shared decision with their healthcare provider (HCP). Approximately half of patients reported that their OAC treatment decisions were made entirely by their HCP. Compared with those reporting no SDM, patients reporting SDM for OAC were more often female (47.2% vs. 38.4%), while patients reporting SDM for rhythm control were more often male (62.2% vs. 57.6%). The most important factors cited by patients during decision-making for OAC were reducing stroke and bleeding risk, and their HCP’s recommendations. After adjustment, patients with self-reported understanding of OAC, and rhythm control options, had higher odds of having participated in SDM [odds ratio (OR) 2.54, confidence interval (CI): 1.75–3.68 and OR 2.36, CI: 1.50–3.71, both P ≤ 0.001, respectively]. Conclusion Shared decision-making is not widely implemented in contemporary AF practice. Patient understanding about available therapeutic options is associated with a more than a two-fold higher likelihood of SDM, and may be a potential target for future interventions.