Peterson, Eric D.

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 use of evidence-based therapies to treat cardiovascular comorbidities and risk factors in patients with AF in outpatient clinical practice has not been well characterized. Methods: Using a large, community-based registry of patients with AF in the United States, the prevalence of cardiovascular comorbidities and corresponding use of evidence-based therapies were determined. Results: Among 9,589 enrolled patients with AF, the median age was 75 years; 57.8% were male; 10.7% were non-white; 69.9% had Medicare or Medicaid; 31.8% had coronary heart disease, 32.2% had heart failure, 13.0% had peripheral vascular disease, and 29.5% had diabetes mellitus. Among eligible patients, 62.8% of 3,612 were prescribed an antiplatelet agent, 72.1% of 4,674 were prescribed a β-blocker, 59.7% of 5,121 were prescribed an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, 15.7% of 624 were prescribed an aldosterone antagonist, 70.1% of 6,914 were prescribed a statin, 94.7% of 8,329 were prescribed an antihypertensive, 58.3% of 504 had an ICD, and 44.5% of 9,589 received all indicated evidence-based therapies ( Table ). Conclusion: Cardiovascular comorbidities and risk factors in patients with AF are often inadequately treated with evidence-based therapies in the outpatient practice setting, underscoring opportunities to improve care for patients with AF.

Background: One month following a myocardial infarction (MI), more than a third of older adults (age ≥65 years) are frail as demonstrated by slow gait speed (≤ 0.65 m/sec). The prognostic significance of frailty in a cardiovascular population in terms of future health states is unknown. Methods: The TRIUMPH longitudinal registry enrolled 1314 older adults (age ≥65 years) following an acute MI from 24 US centers. Gait speed (m/sec) was determined at one month (to allow for acute recovery) in 329 patients with in-home follow up. Using averages of 3 timed walks over 15-feet, patients were stratified by gait speed into 2 groups: slow (<0.65m/sec) and preserved (≥0.65m/sec). One year basic (mobility, self care) and instrumental activities of daily living (ADL) (phone, meds, travel, money), physical function score (SF12 PCS), quality of life (Seattle Angina Questionnaire (SAQ)), and mortality were assessed. Results: Slow gait speed was present in 38% (N=126) of older adults at 1 month. At 1 year, despite similar survival, frail adults were much more likely to need help with basic and instrumental (ADL), and had lower physical function and quality of life (QOL) compared to non-frail adults. ( table ) Slower gait speed remained a significant predictor of worse physical function at 1 year after adjustment for baseline physical function (p=0.013). Conclusions: Frailty is common in older adults following an MI, and those with frailty are at substantial risk for continued impairment over time. Understanding the mechanisms or reversibility of this vulnerable state would contribute to optimization of independence and quality of life among older adults with cardiovascular disease. Frailty Post MI and 1 Year Outcomes Frail (Gait <0.65m/sec)N=126 Not Frail (Gait ≥0.65m/sec)N=203 P value Mobility ADL (% need help) 45 23 <0.001 Self-Care ADL (% need help) 11 4 <0.001 Instrumental ADLs (% need help) 36 19 0.003 Physical Function (PCS) 39.2 ± 12.0 47.2 ± 9.7 <0.001 SAQ Quality of Life (QOL) 88.0 ± 15.9 91.3 ± 12.1 0.061 Mortality (%) 5.6 4.5 NS

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: Prior ATPIII lipid guidelines recommended statin therapy for patients with clinical ASCVD to achieve low density lipoprotein cholesterol (LDL-C) targets, while the 2013 ACC/AHA lipid guidelines recommend high-intensity statin therapy for all ASCVD patients. How closely these recommendations are followed in routine clinical practice is unknown. Methods: We evaluated statin use, intensity, and LDL-C values in 1,483 patients with ASCVD (coronary heart disease, cerebrovascular disease, and peripheral arterial disease) enrolled and seen serially at 62 geographically dispersed US cardiology and primary care clinics in the Patient and Provider Assessment of Lipid Management (PALM) Registry between May - September 2015. Factors associated with high intensity statin use (atorvastatin ≥40 mg or rosuvastatin ≥20 mg daily) and LDL-C <70 mg/dL were evaluated in multivariable logistic regression. Results: Of 1,483 ASCVD patients, 86.2% were on a statin, but only 31.4% were on a high-intensity statin. Overall, 64.0% had an LDL-C <100 mg/dL, but only 29.0% had an LDL-C <70 mg/dL. Factors associated with high-intensity statin use in multivariable regression were younger age (OR 0.74 per 10 year increase, p<0.001, 95% CI 0.66-0.83), male sex (OR 1.69, p<0.001, 95% CI, 1.32-2.16), cerebrovascular disease (OR 1.55, p=0.008, 95% CI 1.12-2.13), coronary heart disease (OR 2.42, p<0.001, 95% CI 1.67-3.50), and being seen by a cardiologist (OR 1.35, p =0.04, 95% CI 1.01-1.81). Factors associated with an increased likelihood of LDL-C<70 were male sex (OR 1.55, p=0.001, 95% CI 1.20-2.01), white (OR 1.62, p=0.03, 95% CI 1.04-2.5-, diabetes (OR 1.64, p<0.001, 95% CI 1.29-2.09) and being seen by a cardiologist (OR 1.94, p<0.001, 95% CI 1.41-2.67). Discussion: Substantial gaps in care remain for secondary prevention of ASCVD despite simplified recommendations. While the majority of patients with ASCVD in community practice are on a statin, only one-third are on high intensity statins and over two-thirds have LDL ≥70 mg/dL.

Introduction: Warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran are effective for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). However, few analyses have compared persistence rates of warfarin vs. dabigatran-treated patients. Methods: The ORBIT-AF registry enrolled patients with AF from 173 clinical practices across the US. One-year persistence of warfarin vs. dabigatran was defined as treatment at baseline visit and at 1-year follow-up. Multivariable logistic regression analysis was used to identify characteristics associated with warfarin or NOAC persistent use. Results: At baseline, 6.4% (N=459/7,150) were treated with dabigatran and 93.6% (N=6,691/7,150) with warfarin. Patients treated with warfarin at baseline were older (74 vs. 71, p<.0001), had more NYHA class III/IV heart failure (7 vs. 5, p=.0007), lower creatinine clearance (77 vs. 88, p<.0001), higher CHA2DS2-VASc risk scores, and more prior CVA/TIA events (16 vs. 11, p=.003). Patients treated with dabigatran had more severe symptoms (EHRA class III: 20 vs. 14, p<.0001), higher rates of treatment with a rhythm control strategy (42.7 vs. 28.2, p<.0001), more attempts at cardioversion (38.3 vs. 32.1, p<.006), and catheter ablation of AF (9.8 vs. 5.2, p<.0001). At 12 months, adjusted persistence rates for warfarin were higher than dabigatran [82% (80-84) vs. 67% (61-73) p<.0001]. Factors independently associated with one year persistence were: African American race (OR 1.53, 95% C.I. 1.07-2.19, p=0.02), Hispanic race (OR 1.66, 95% C.I. 1.06-2.60), paroxysmal AF (vs. new onset) (OR 1.68, 95% C.I. 1.21-2.33, p=.002), LVH (OR 1.40, 95% C.I. 1.08-1.81, p=.01), persistent AF (vs. new onset) (OR 1.91, 95% C.I. 1.35-2.69, p=.0002), and CHA2DS2-VASc risk scores ≥ 2 (OR 1.94, 95% C.I. 1.18-3.19, p=.009). Conclusion: Persistence rates for warfarin were higher at one year than those on dabigatran. In addition, factors associated with persistence of warfarin include: African American and Hispanic race, type of AF including permanent and persistent, LVH, and CHA2DS2-VASc risk scores ≥ 2.

Background: Little is known about whether insurance status affects the presentation and treatment of patients with atrial fibrillation (AF). Methods: We used data from the ORBIT-AF Registry (2010 - 2011), a national, large outpatient registry, to evaluate clinical characteristics and oral anticoagulation (OAC) use. We examined differences in comorbidities and receipt of OAC among patients enrolled in the Medicaid program at baseline compared with those not enrolled in Medicaid. After restricting to patients who were taking OAC, we compared receipt of novel oral anticoagulants (dabigatran or rivaroxaban) versus warfarin by Medicaid status during 2 years of followup. We used logistic regression models adjusting for demographic and clinical covariates to evaluate baseline OAC receipt by Medicaid status. Results: Of 10,133 patients, N=470 (4.6%) were classified as having Medicaid insurance. Compared with those with other insurance, Medicaid patients were younger (70.0 years; IQR=61.0 - 79.0 vs. 75.0 years; IQR=67.0 - 82.0), more likely to be female (53.0% vs. 41.8%), and less likely to be white (58.7% vs. 90.7%; all p<0.001). Medicaid patients had higher rates of smoking, prior stroke/TIA, diabetes, hypertension, and HF. Medicaid patients were less likely to be taking OAC at baseline, a difference that was particularly pronounced for high stroke risk patients (CHADS2>=2, p<0.001; Table). Among those on anticoagulation, Medicaid patients were less likely to receive NOAC over 2 years of followup. In adjusted analyses, Medicaid patients were less likely to receive OAC at baseline, but this difference was not statistically significant (HR = 0.82; 95% CI = 0.61, 1.09). Among untreated patients with CHADS2>=2, Medicaid patients were more likely than patients with other insurance to have “unable to adhere/monitor” listed as a contraindication to OAC (p<0.001). Conclusions: In a contemporary, community-based AF cohort, Medicaid patients had a greater comorbidity burden and higher stroke risk, yet were less likely to receive OAC compared with those with other forms of insurance.

Background: Novel therapies for stroke prevention in atrial fibrillation (AF) are emerging. However, data on use and outcomes of these agents in the community are limited, particularly in patients newly diagnosed with AF or recently transitioned to a novel anticoagulant. Methods: Phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF II) is a multicenter, national, AF registry. We are enrolling 15,000 patients with new-onset AF, or those with known AF recently-transitioned to a novel anticoagulant. The primary objective is to evaluate the safety of novel anticoagulants, with specific focus on use, transitions, and management around invasive procedures and bleeding events. An adaptive design is used to ensure diversity of enrollment across geographic, provider, and treatment groups. The primary outcomes are major bleeding and thromboembolic events. Results: Of 1,011 patients in ORBIT-AF II, the median age was 73, 44% were female, 23% had a history of heart failure, 34% had a prior MI, and 11% had a prior stroke/TIA. The mean CHADS2 score was 2. Overall, 76% had AF new-onset, and a range of anticoagulant strategies was used in these patients (Figure). Among the 24% with known AF transitioned to a novel agent, 66% received rivaroxaban, versus 8.1% dabigatran, and 26% apixaban. Compared with patients having new-onset AF, those with known AF recently-transitioned to a novel anticoagulant were slightly older (median age 74 vs. 72), had higher CHADS2 scores (>2 in 70% vs. 62%), but less severe kidney disease (0 vs. 1.7%). Conclusions: Patients with new-onset AF are frequently treated with novel anticoagulants and these patients have lower risk scores than those with known AF transitioned to a novel drug. These data will provide insights into clinical management and patient centered outcomes among those treated with novel anticoagulants in real world practice settings.

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.

Background Oral anticoagulation (OAC) can reduce stroke risk at the cost of increased bleeding risk in those with atrial fibrillation (AF). Observational data have shown that higher-risk patients with AF most likely to benefit from OAC are less likely to receive OAC at hospital discharge. Methods We used data from ORBIT-AF Registry, a cohort of 9,589 AF patients enrolled among 173 participating outpatient practices. OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using the CHADS2 and ATRIA scores, respectively. Results The study population had a mean age of 73.5 years; 57.8% were men. Overall, 76.4% of patients received OAC. Use of OAC rose with increasing CHADS2 stroke risk, from 67% for CHADS2 <1 to 80% for CHADS2 ≥2 (p<0.0001). OAC use fell slightly with increasing ATRIA bleeding risk, from 77% for ATRIA score ≤3 to 74% with ≥5 (p=0.002 for trend). Among patients with low bleeding risk, rates of OAC increased commensurate with stroke risk (p<0.0001 for interaction; see figure). Higher bleeding risk tended to decrease rates of OAC among patients with a CHADS2 score ≥2 (p=0.13 for interaction). Conclusions In community-based outpatients with AF, use of OAC rose with increasing thromboembolic risk and declined with higher bleeding risk. These findings suggest that the risk-treatment paradox may be less that previously reported. Provision of OAC in community practice appears to appropriately consider patients' stroke and bleeding risks. Further research is required to understand how quality improvement initiatives can further improve stroke prevention.