Gersh, Bernard J.

Objective To investigate the association of mitral regurgitation (MR) on thromboembolic risk of patients with non-valvular atrial fibrillation (NVAF) undergoing transoesophageal echocardiography (TEE)-guided cardioversion. Methods Data for consecutive patients who underwent TEE-guided cardioversion for NVAF between 2000 and 2012 were analysed. MR severity was assessed by Doppler echocardiography and classified as ≤mild, moderate or severe. Left atrial appendage emptying velocities were averaged for five consecutive cycles. Multivariable regression models were used to identify independent predictors of left atrial appendage thrombus (LAAT) and stroke. Results 2950 patients (age, 69.3±12.2 years, 67% men) were analysed. 2173 (73.7%) had ≤mild MR; 631 (21.4%), moderate MR; and 146 (4.9%), severe MR. Patients with moderate (age, 72.4±10.7 years) and severe (age, 72.8±12.1 years) MR were older than those with ≤mild MR (age, 68.2±12.5 years). The prevalence of LAAT was 1.5% (n=43). CHA 2 DS 2 -VASc scores (≤mild MR, 3.0±1.6; moderate MR, 3.5±1.5; severe MR, 3.9±1.5; p<0.001) and heart failure frequency (≤mild MR, 38.4%; moderate MR, 48.0%; severe MR, 69.2%; p<0.001) were increasingly higher with greater MR severity. Multivariable logistic regression analysis showed no association of moderate MR (OR 0.77, 95% CI 0.38 to 1.56) or severe MR (OR 0.55, 95% CI 0.21 to 1.49) with LAAT. During a mean follow-up of 7.3±5.1 years (median 7.5, IQR, 2.7–10.9), 216 patients had an ischaemic stroke. Adjusted Cox regression analysis showed no significant association of moderate MR (HR 1.22, 95% CI 0.88 to 1.68) or severe MR (HR 0.73, 95% CI 0.31 to 1.46) with stroke. Conclusions Among patients with NVAF, the presence or severity of MR was not associated with a decreased risk of LAAT or stroke.

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.

Abstract Introduction Non-vitamin-K oral anticoagulants (NOACs) were recommended in preference to oral vitamin K antagonists (VKAs) in the 2020 updated guidelines for stroke prevention in atrial fibrillation (AF), from the European Society of Cardiology (ESC). Rivaroxaban is a NOAC that is approved in many countries worldwide for reducing the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). Purpose To explore the baseline characteristics, dosing and 2-year outcomes of patients with AF treated with rivaroxaban. Methods RIVaroxaban Evaluation in Real Life setting (RIVER) is a prospective international, multicenter registry of patients with newly diagnosed non-valvular AF treated with rivaroxaban for the prevention of thromboembolic stroke and at least one investigator-determined risk factor for stroke. Results A total of 5043 patients were enrolled into RIVER between January 2015 and June 2017. Mean (SD) age at diagnosis was 69.5 (11.0) years and 55.7% were males. Caucasian patients represented the largest proportion of patients in RIVER (80.3%), followed by Asians (5.5%) and hispanic/latino (3.7%). Almost all patients (98.5%) were prescribed a single daily dose of rivaroxaban, most commonly 20 mg (77.3%) and 15 mg (20.4%), while a 10 mg dose was prescribed in only 2.3% of patients. During the 2-year follow-up, the rates (95% CI) of all-cause mortality, stroke/SE, and major bleeding were 2.75 (2.43 to 3.12), 0.89 (0.72; 1.11), and 1.26 (1.05 to 1.52) per 100 person years, respectively (Figure 1). The most common cardiovascular cause of death was congestive heart failure (30.4%) and myocardial infarction (11.4%). Leading non-cardiovascular causes of death were malignancy (27.4%), respiratory failure (18.9%) and infections/sepsis (13.2%). Over 2 years, 710 (14.1%) of patients discontinued rivaroxaban. The corresponding proportions at 6 months and 1 year were 7.8% and 10.8%, respectively. Out of all the patients who discontinued, 62 (8.7%) restarted rivaroxaban during their follow-up (Table 1). Conclusion During 2 years of follow up in the international, prospective RIVER registry, rivaroxaban treatment for AF was associated with low rates of stroke or major bleeding. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

Abstract Introduction Rivaroxaban is recommended as an option for anticoagulation in patients with nonvalvular atrial fibrillation (AF) with one or more risk factors for stroke. The approved/recommended rivaroxaban dose for stroke prevention in patients with atrial fibrillation (AF) is solely based on renal function: 20 mg once daily (od) for patients with a creatinine clearance [CrCl] ≥50 ml/min and 15 mg od in patients with CrCl 15–49 mL/min). Purpose To assess the patterns of rivaroxaban prescription as per the creatinine clearances levels and to assess the impact of the rivaroxaban dosing on the rate of events at 2-year follow-up in patients with AF. Methods RIVaroxaban Evaluation in Real Life setting (RIVER) is a prospective international registry of patients with newly diagnosed non-valvular AF treated with rivaroxaban for the prevention of thromboembolic stroke and at least one investigator-determined risk factor for stroke. Adjusted hazard ratios (HRs) were obtained through Cox proportional-hazard model. Results Among 3402 patients with normal renal function (CrCl ≥50 mL/min), 82.1% were prescribed the recommended rivaroxaban dose of 20 mg (od) at baseline. Among 524 patients with moderate or severe renal impairment (CrCl 15–50 mL/min), 55.3% patients received rivaroxaban 15 mg (od), 39.9% received 20 mg (od) and 4.2% 10 mg (od). Non-recommended dosing was rare in patients younger than 70 (13.5%) but more frequent in older patients (28.8%). Non-recommended low dosing was more frequent in Asians (38.9%), compared to non-Asian patients (13.8%). Regarding clinical outcomes, adjusted hazards ratios (HR, presented with 95% confidence intervals) showed that the non-recommended low dosing (&lt;20 mg od) was associated with higher risk of non-cardiovascular mortality (HR 2.09 (1.16–3.77)) in patients with normal renal function. The non-recommended high dosing (&gt;15 mg od) was associated with lower risk of all-cause mortality (HR 0.63 (0.42–0.93)) and cardiovascular mortality (HR 0.32 (0.13–0.77)) and higher risk of major bleeding (HR 2.86 (1.49–5.50)) in patients with moderate to severe renal impairment (figure 1 and 2). Conclusion In patients with normal renal function, non-recommended low dose rivaroxaban was associated with increased cardiovascular mortality without reducing the risk of major bleeding compared to recommended dosing. In patients with CrCl &lt;50 ml/min, non-recommended high dose rivaroxaban was associated with reduced cardiovascular mortality but at the cost of increased major bleeding. These observational data largely support the reduction of rivaroxaban dosing according to renal function but educational strategies are needed to ensure that rivaroxaban is used appropriately. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the RIVER registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

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.

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.