Ezekowitz, Michael D.

Background: The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire has recently been validated to measure the impact of atrial fibrillation on quality of life, but a clinically important difference in AFEQT score has not been well defined. Methods and Results: To determine the clinically important difference in overall AFEQT (score range= 0 [worst] to 100 [best]) and selected subscales, we analyzed data in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry, a United States-based outpatient atrial fibrillation registry. AFEQT was assessed at baseline and 1 year in a subset of 1347 ORBIT-AF patients from 80 US sites participating in ORBIT-AF from June 2010 to August 2011. The mean change method was used to relate changes in 1-year AFEQT scores to clinically important changes in the physician assessment of European Heart Rhythm Association functional status (1 class improvement and separately 1 class deterioration). Clinically important differences and 95% CI corresponding to either a 1 European Heart Rhythm Association class improvement or deterioration were 5.4 (3.6–7.2) and −4.2 (−6.9 to −1.5) AFEQT points, respectively. Similarly, clinically important difference values were seen for a 1 European Heart Rhythm Association class improvement for the AFEQT subscales Activities of Daily Living and Symptoms: 5.1 (2.5–7.6) and 7.1 (5.3–9.0) AFEQT points, respectively. Conclusions: Based on the anchor of 1 European Heart Rhythm Association class change, changes in AFEQT score of + or −5 points are clinically important changes in patients’ health. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT01165710.

Introduction: Shared decision making (SDM) incorporates patient and physician values and preferences into treatment selection. While multiple therapeutic options are available for stroke prevention in atrial fibrillation (AF), few studies have examined factors associated with SDM regarding choice of antithrombotic strategy. Methods: We evaluated survey data from 1006 patients with new-onset AF enrolled at 56 sites participating in a substudy of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT II), an outpatient AF registry in the US. Patients were asked: “When choosing your blood thinner(s), who made this treatment decision?”, and SDM was defined as a response of “equally me and my healthcare provider (HCP)”, “mostly me” or “entirely me”, while no SDM was defined as a response of “mostly my HCP” or “entirely my HCP”. Multivariable logistic regression models evaluated associations between 13 patient-level factors, self-reported understanding of treatment options, and SDM for antithrombotic therapy. Results: Most patients allowed their HCP to make the therapeutic decisions on antithrombotic strategy, with 246 (24.5%) reporting SDM. Patients reporting SDM were more often female (47.2% vs. 40.5%) and were more frequently insured by Medicare (40.2% vs. 34.5%) than patients reporting no SDM. Among patients taking warfarin, median time in therapeutic range was higher among patients reporting SDM than among those not reporting SDM. In multivariable models, chronic obstructive pulmonary disease was associated with lower odds of SDM while self-reported understanding of blood thinner options was associated with higher odds of SDM (Table). Conclusion: One in four patients in an outpatient AF registry reported that their current antithrombotic strategy was the result of a shared decision making process. Additional work is need to determine whether patient-reported SDM is associated with medication adherence and outcomes of therapy.

Objective The association with B-type natriuretic peptide (BNP), disease progression and outcomes in patients with atrial fibrillation (AF) has not been thoroughly investigated. Methods We evaluated the association between BNP levels and outcomes, including AF progression, composite outcome of major adverse cardiovascular or neurological events (MACNE) and major bleeding, via pooled logistic regression and Cox frailty models in Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry. AF progression was defined as either paroxysmal becoming persistent or permanent, or persistent becoming permanent at any follow-up. Results Among 13 375 patients with AF, 2797 with BNP values at baseline (median age (IQR), 72.0 (63.0–80.0) years; 43.0% women; median BNP, 238 (102–502) ng/L; 42.3% prior heart failure) were included in the models evaluating the association between BNP levels and MACNE or major bleeding. Of these, 1282 patients with paroxysmal or persistent AF at baseline were analysed in AF progression model. The likelihood of AF progression (adjusted OR, 1.11 for every 100 ng/mL; 95% CI 1.03 to 1.19) and MACNE (adjusted HR, 1.11 for every doubling in BNP values; 95% CI 1.01 to 1.22) increased with BNP concentration, while the elevated BNP values were not associated with increased risks of major bleeding. BNP values improved the risk prediction of AF progression and MACNE when added to conventional risk estimates. Conclusions BNP levels are associated with increased risk of AF progression and cardiovascular outcomes in patients with AF. Further studies are required to assess whether biomarker-based risk stratification improves patient outcomes. Clinical trial registration NCT01701817 .

Background: Bleeding is commonly cited as a reason for stopping oral anticoagulants (OACs). Whether minor bleeding events (nuisance bleeding, NB) in patients with atrial fibrillation on OACs are associated with OAC discontinuation, major bleeding, and stroke/systemic embolism (SSE) is unknown. Methods: Within the ORBIT-AF prospective, outpatient registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we identified 6771 patients ≥18 years of age at 172 sites with atrial fibrillation and eligible follow-up visits. NB was ascertained from the medical record and was defined as minor bleeding that did not require medical attention (eg, bruising, hemorrhoidal bleeding). We used multivariable pooled logistic regression modeling to evaluate the associations between NB and major bleeding and SSE in the 180 days after documentation of NB. Our unit of analysis was the patient visit, occurring at ≈6-month intervals for a median of 1.5 years following enrollment. Changes in anticoagulation treatment satisfaction after NB were examined descriptively in a subset of patients. Results: The median age of the overall population was 75.0 (interquartile range, 67.0–81.0); 90.0% were white and 42.5% were female. Among 6771 patients (18 560 visits), n=1357 (20.0%) had documented NB, for an incidence rate of 14.8 events per 100 person-years. Over 96.4% of patients remained on OAC therapy after the NB event. Overall, 287 (4.3%) patients experienced major bleeding and 64 (0.96%) had a SSE event during follow-up. NB was not associated with a significant increased risk of major bleeding over 6 months in models adjusting for the ATRIA bleeding score (Anticoagulation and Risk Factors in Atrial Fibrillation) (odds ratio, 1.04; 95% confidence interval, 0.68–1.60; P =0.86). NB was also not associated with increased SSE risk over 6 months in models adjusting for the CHA 2 DS 2 -VASc risk score (odds ratio, 1.24; 95% confidence interval, 0.53–2.91; P =0.62). Conclusions: NB is common among patients with atrial fibrillation on OACs. However, NB was not associated with a higher risk of major bleeding or SSE over the next 6 months, suggesting its occurrence should not lead to changes in anticoagulation treatment strategies in OAC-treated patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Background Non–vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice. Methods and Results We analyzed data from the ORBIT‐AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow‐up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84, P <0.0001) and had lower ORBIT bleeding risk scores (26% ≥4 versus 45%, P <0.0001). Compared with those appropriately receiving standard dosing, patients receiving inappropriately reduced‐dose NOACs had higher unadjusted rates of thromboembolic events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95% confidence interval 0.92‐2.67) and death (6.77 versus 2.60, hazard ratio 2.61, 95% confidence interval 1.86‐3.67). After adjustment, outcomes were not significantly different but tended to favor patients dosed appropriately. Conclusions The majority of dose reductions of NOACs in AF are inconsistent with US Food and Drug Administration recommendations. There appear to be opportunities to improve current NOAC dosing in community practice. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01701817.

Objective To describe self-reported disease understanding for newly diagnosed patients with atrial fibrillation (AF) and assess (1) how disease understanding changes over the first 6 months after diagnosis and (2) the relationship between patient understanding of therapies at baseline and treatment receipt at 6 months among treatment-naïve patients. Methods We analysed survey data from SATELLITE (Survey of Patient Knowledge and Personal Priorities for Treatment), a substudy of patients with new-onset AF enrolled in the national Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT) II registry across 56 US sites. Patients were surveyed at the baseline and 6-month follow-up clinic visits using Likert scales. Results Among 1004 baseline survey responses, patients’ confidence in their understanding of rhythm control, ablation, anticoagulation and cardioversion was suboptimal, with ‘high’ understanding ranging from 8.5% for left atrial appendage closure to 71.3% for rhythm therapy. Of medical history and demographic factors, education level was the strongest predictor of reporting ‘high’ disease understanding. Among the 786 patients with 6-month survey data, significant increases in the proportion reporting high understanding were observed (p<0.05) only for warfarin and direct oral anticoagulants (DOACs). With the exception of ablation, high understanding for a given therapeutic option was not associated with increased use of that therapy at 6 months. Conclusions About half of patients with new-onset AF understood the benefits of oral anticoagulant at the time of diagnosis and understanding improved over the first 6 months. However, understanding of AF treatment remains suboptimal at 6 months. Our results suggest a need for ongoing patient education. Clinical trial registration Clinicaltrials.gov. Identifier: NCT01701817.

Background Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P <0.0001), more likely to be white (92% versus 89%, P =0.005), more likely to have private insurance (33% versus 25%, P <0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P <0.0001). They had more new‐onset atrial fibrillation (8.8% versus 4.1%, P <0.0001), lower CHADS 2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P <0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P <0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow‐up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P =0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P <0.0001). Conclusions Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. Clinical Trial Registration URL : Clinicaltrials.gov. Unique identifier: NCT 01165710.