Simon, DaJuanicia N.

Background: Little information exists on clinical characteristics and treatment patterns of patients with atrial fibrillation (AF) following a major bleeding event in clinical practice. Methods: We used data from a large, national outpatient registry, ORBIT-AF (2010 – 2011), to evaluate event characteristics and oral anticoagulation (OAC) management following a major bleeding event. Major bleeds were defined according to ISTH criteria. We compared baseline characteristics among patients who persisted on OAC therapy at the first clinic visit following a major bleed and those in whom OAC was discontinued using chi-squared tests. Results: Of 10135 patients enrolled in ORBIT-AF, n=791 (7.8%) bleeding events occurred during 2 years of follow-up. Among patients who were receiving OA, n=632 (3.5 per 100 person years) experienced a major bleed. Of these, 67.3% experienced a fall in hemoglobin and 46.8% required transfusion of 2 of more units of red blood cells. Critical site bleeding occurred in 150 OAC patients, with the majority of these classified as intracranial bleeding (n= 89), followed by retroperitoneal (n=25) and intraocular (n=17). Fatal bleeds occurred in 37 patients (5.9% of all major bleeds). Nearly one-third of patients (31.0%) discontinued OAC therapy following the major bleeding event. Compared with those who persisted on OAC, patients who discontinued OAC were more likely to have hypertension and CKD. Those who discontinued OAC were more likely to have gastrointestinal or CNS site bleeding compared with those who persisted (Table). Conclusions: One in three patients who experienced a major bleed were no longer optimally anticoagulated after the event. Those who discontinued OAC had a greater comorbidity burden and more likely to have bleeding in a critical site those who persisted on OAC.

Background: The Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) survey has recently been validated to measure the impact of atrial fibrillation on patients’ quality of life, but a clinically important difference (CID) in AFEQT score has not been defined. Knowing the CID is needed to interpret the meaningfulness of differences between treatments in clinical trials; or patient populations for quality assessment. Objectives: To calculate CID values in AFEQT in the ORBIT registry. Methods: ORBIT-AF is a US-based outpatient AF registry that measured disease-specific QoL with the AFEQT tool (score range= 0 (worst) to 100) at baseline and at 1 year follow-up. Two anchor-based methods were used to relate changes in AFEQT to clinically important differences in the more established European Heart Rhythm Association (EHRA) measure of functional status. Ranging from 1 (no symptoms) to 4 (disabling), a change of 1 EHRA class was defined as an important change in the anchor. Both the mean change and receiver operating characteristics (ROC) methods were then used to identify CIDs in AFEQT at 1 year follow-up. This was done for both improvement and worsening on the anchor. The mean change method defines a CID as the mean change in AFEQT score among patients with a 1 EHRA class change. The ROC method identifies a CID as the point on the ROC curve that best discriminates patients who experienced an important change in the anchor (≥ 1 EHRA class change) from those who experienced no change. Results: AFEQT was assessed in 2008 AF patients at baseline and 1347 patients at 1 year from 99 US sites participating in ORBIT-AF. CIDs and 95% confidence intervals (CI) corresponding to an improvement in EHRA for the mean change method were 5.4 (3.6, 7.2) AFEQT points and 1.9 (0.4, 9.3) AFEQT points for the ROC method. CIDs corresponding to worsening in EHRA for the mean change method were -4.2 (-6.9,-1.5) AFEQT points and -7.4 (-13.9,-4.6) AFEQT points for the ROC method. Conclusions: Changes in AFEQT as small as 2 points may be clinically relevant, although CIDs vary depending on the method of calculation. The variability suggests identifying a single universal CID to assess improvement in quality of life in AF patients may not be ideal and improvement may relate to the nature of a patient’s symptoms and their baseline level of activity.

Background: Oral anticoagulation (OAC) is effective at preventing stroke in patients with atrial fibrillation (AF), yet warfarin is often poorly tolerated. Non-vitamin K oral anticoagulants (NOACs) are as or more effective as warfarin, yet their tolerance and persistence in clinical practice is not known. Methods: We assessed patterns of persistent OAC use among 2,345 AF patients starting on therapy in the ORBIT-AF II registry (71% starting on a NOAC, and 29% on warfarin). Results: By 6 months, 364 (22%) patients started on a NOAC had discontinued or changed initial therapy versus 143 (21%) started on warfarin initially (p=0.5). Among warfarin users, patients who switched or discontinued therapy were of similar age (median ages 72 and 74 vs. 74 for stable users, p=0.7) and CHA2DS2-VASc scores (mean 98 and 3.66 vs. 3.84, p=0.4). Among NOAC users, those who discontinued treatment were younger (median age 68 vs. 73 for those who switched and 72 for stable users; p=0.0004), and lower CHA2DS2-VASc scores (3.02 vs. 3.58 and 3.47, respectively; p=0.0008). The median time to change or discontinuation was more rapid in those started on a NOAC vs warfarin (97 days vs. 122 days, p=0.003). Among those on warfarin at baseline, 7.6% (n=52) were switched to a NOAC within 6 months, whereas transitions from NOAC to warfarin was 2.5% (n=42).Transitions among NOACs occurred in 9.8%, 3.2%, and 5.5% of patients on baseline dabigatran, rivaroxaban, and apixaban, respectively. Physician preference was the most common reason for both OAC and warfarin changes (Table). Drug cost was the primary reason for change of therapy in 15% of NOAC users (vs. 0 for warfarin). Conclusions: At 6-month follow-up, one in five newly started on OAC had discontinued or changed. These rates of change were similar among warfarin and NOAC treated patients. Cost concerns drove discontinuation in a modest number of patients, however, cost concerns were more prevalent in NOAC-treated patients.

Background: Non-vitamin K oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the frequency of major bleeds on NOACs and how these events are managed in clinical practice. Methods: We assessed the rates, management, and outcomes of ISTH major bleeding events among AF patients in the ORBIT-AF II registry (mean follow-up 213 days). Results: Overall, 103 patients experienced 110 major bleeding events during follow-up n=90/4986 (1.8%) on NOAC, and n=20/1320 (1.5%) on warfarin. Patients with bleeding events on NOAC were slightly younger than those on warfarin (median age 76 vs. 80; p=0.2). Among mutually-exclusive bleeding types, intracranial bleeding was more common in warfarin treated patients than NOAC-treated (15% vs 6.7%), whereas GI bleeding was more common on NOACs (56% vs. 40%, overall p=0.1 for bleeding type). Management of bleeding differed by anticoagulation type: blood products and reversal agents were more commonly used in patients on warfarin (Table). No patient received prothrombin complexes, recombinant factor VIIa, aminocaproic acid, tranexamic acid, aprotinin, or desmopressin. Out of 90 major bleeding events in NOAC patients, only 1 was fatal (1%). Within 30 days following bleeding, there were no strokes and 1 TIA (NOAC). Following a major bleed, the recurrent bleeding rate in NOAC patients in the next 30-days was 4% and the death rate was 4%. Conclusions: Rates of major bleeding with NOACs in clinical practice are comparable to those reported in clinical trials. Compared with warfarin, bleeding among NOAC users was less likely intracranial and more likely to be GI. Management of bleeding in the setting of NOAC rarely includes reversal agents.

Background: With increasing options for treating atrial fibrillation (AF), it is important to understand and quantify patient symptoms and quality of life (QoL), as improving symptoms and maximizing QoL are primary treatment goals. However, little is known about the factors associated with QoL. Methods: The Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) is a disease-specific QoL tool for AF, with domain and summary scores ranging from 0 (the worst health status) to 100. Using hierarchical pseudo-binomial regression, we evaluated factors associated with baseline AFEQT Summary and Subscale scores in the ORBIT AF registry. Adjusted associations were reported as odds ratios (OR) and 95% confidence intervals (CI). Results: AFEQT was assessed in 2,007 AF outpatients from 99 sites. Median age and interquartile range (IQR) was 76 (67-82); 43% were female; and the median CHA2DS2-VASC score was 4 (3-5). Median AFEQT summary score was 82 (67, 94). Median symptom score was 92 (78-100) and daily activity score was 77 (52-94). Female sex, younger age, new onset AF, higher heart rate, obstructive sleep apnea, and CAD were all associated with reduced QoL. (Table) Similar trends were seen for the symptoms subscale: female sex [OR 0.57 CI (0.48, 0.68)], younger age [OR 1.10 CI (1.06, 1.15)], and new onset AF [OR 0.55 CI (0.43, 0.70)] were associated with worse symptoms. Likewise, for the daily activities subscale, Other race [OR 0.54 CI (0.36-0.80)] and higher BMI [OR 0.98 CI (0.98-0.99)] were associated with decreased activity. Conclusions: In the largest community-based assessment of QoL in patients with AF, we found several patient factors to be associated with low QoL, including female sex, new onset AF, younger age, higher heart rate, and certain cardiopulmonary comorbidities. Understanding patient characteristics associated with worse QoL can be a foundation for eradicating disparities and tailoring treatment.

Background— Current guidelines recommend surgical revascularization (coronary artery bypass graft [CABG]) over percutaneous coronary intervention (PCI) in patients with diabetes mellitus and multivessel coronary artery disease. Few data are available describing revascularization patterns among these patients in the setting of non–ST-segment–elevation myocardial infarction. Methods and Results— Using Acute Coronary Treatment and Intervention Outcomes Network Registry–Get with the Guidelines (ACTION Registry–GWTG), we compared the in-hospital use of different revascularization strategies (PCI versus CABG versus no revascularization) in diabetes mellitus patients with non–ST-segment–elevation myocardial infarction who had angiography, demonstrating multivessel coronary artery disease between July 2008 and December 2014. Factors associated with use of CABG versus PCI were identified using logistic multivariable regression analyses. A total of 29 769 patients from 539 hospitals were included in the study, of which 10 852 (36.4%) were treated with CABG, 13 760 (46.2%) were treated with PCI, and 5157 (17.3%) were treated without revascularization. The overall use of revascularization increased over the study period with an increase in the proportion undergoing PCI (45% to 48.9%; P trend =0.0002) and no change in the proportion undergoing CABG (36.1% to 34.7%; p trend =0.88). There was significant variability between participating hospitals in the use of PCI and CABG (range: 22%–100%; 0%–78%, respectively; P value <0.0001 for both). Patient-level, but not hospital-level, characteristics were statistically associated with the use of PCI versus CABG, including anatomic severity of the disease, early treatment of adenosine diphosphate receptor antagonists at presentation, older age, female sex, and history of heart failure. Conclusions— Among patients with diabetes mellitus and multivessel coronary artery disease presenting with non–ST-segment–elevation myocardial infarction, only one third undergo CABG during the index admission. Furthermore, the use of PCI, but not CABG, increased modestly over the past 6 years.

Background— Instruments to assess symptom burden and quality of life among patients with atrial fibrillation (AF) have not been well evaluated in community practice or associated with patient outcomes. Methods and Results— Using data from 10 087 AF patients in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF), symptom severity was evaluated using the European Heart Rhythm Association (EHRA) classification system, and quality of life was assessed using the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire. The association between AF-related symptoms, quality of life, and outcomes was assessed using Cox regression. The majority of AF patients (61.8%) were symptomatic (EHRA >2) and 16.5% had severe or disabling symptoms (EHRA 3–4). EHRA symptom class was well correlated with the AFEQT score (Spearman correlation coefficient −0.39). Over 1.8 years of follow-up, AF symptoms were associated with a higher risk of hospitalization (adjusted hazard ratio for EHRA ≥2 versus EHRA 1 1.23, 95% confidence interval, 1.15–1.31) and a borderline higher risk of major bleeding. Lower quality of life was associated with a higher risk of hospitalization (adjusted hazard ratio for lowest quartile of AFEQT versus highest 1.49, 95% confidence interval, 1.2–1.84), but not other major adverse events, including death. Conclusions— In a community-based study, most patients with AF were symptomatic and had impaired quality of life. Quality of life measured by the AFEQT correlated closely with symptom severity measured by the EHRA class. AF symptoms and lower quality of life were associated with higher risk of hospitalization but not mortality during follow-up.

Background The characteristics of patients undergoing atrial fibrillation ( AF ) ablation and subsequent outcomes in community practice are not well described. Methods and Results Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation ( ORBIT ‐ AF ), we investigated the prevalence and impact of catheter ablation of AF . Among 9935 patients enrolled, 5.3% had previous AF ablation. Patients with AF ablation were significantly younger, more frequently male, and had less anemia, chronic obstructive pulmonary disease, and previous myocardial infarction (P<0.05 for all analyses) than those without previous catheter ablation of AF . Ablated patients were more likely to have a family history of AF , obstructive sleep apnea, paroxysmal AF , and moderate‐to‐severe symptoms (P<0.0001 for all analyses). Patients with previous ablation were more often in sinus rhythm on entry into the registry (52% vs. 32%; P<0.0001). Despite previous ablation, 46% in the ablation group were still on antiarrhythmic therapy. Oral anticoagulation was prescribed in 75% of those with previous ablation versus 76% in those without previous ablation (P=0.5). The adjusted risk of death (hazard ratio [ HR ], 0.78; 95% confidence interval [ CI ], 0.52 to 1.18; P=0.2) and cardiovascular ( CV ) hospitalization ( HR , 1.06; 95% CI , 0.90 to 1.26; P=0.5) were similar in both groups. Patients with incident AF ablation had higher risk of subsequent CV hospitalization than matched patients without incident ablation ( HR , 1.67; 95% CI , 1.24 to 2.26; P=0.0008). Conclusions In U.S. clinical practice, a minority of patients with AF are managed with catheter ablation. Subsequent to ablation, there were no significant differences in oral anticoagulation use or outcomes, including stroke/non–central nervous system embolism/transient ischemic attack or death. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01165710.