Atrial Fibrillation Use Research Articles

The ETNA-AF Europe registry: 4-year data of edoxaban use in atrial fibrillation in the Italian real world compared to the European cohort

The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years. Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population. In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding. These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

Clinical outcomes in &amp;gt;10,000 Asian vs &amp;gt;61,000 Non-Asian race patients with AF randomized to Warfarin vs DOACs: a patient-level meta-analyses from COMBINE AF

Abstract Background Randomized data comparing clinical outcomes of atrial fibrillation (AF) patients with Asian vs non-Asian races are limited. Methods Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48), we performed an individual patient-level meta-analysis to investigate and compare clinical outcomes of AF patients with self-defined Asian and non-Asian races adjusted for baseline characteristics. Standard-dose direct oral anticoagulants (SD DOAC) were defined as dabigatran 150mg bid; rivaroxaban 20mg (15mg) QD, apixaban 5 mg (2.5 mg) bid, or edoxaban 60 mg (30 mg) QD. Low-dose DOACs (DOACs [LD]) were defined as dabigatran 110 mg bid or edoxaban 30 mg (15mg) QD. Results There were 10,212 pts of Asian race and 61,471 non-Asian races in the COMBINE AF database. Compared with non-Asians, Asians were on average 3.2 yrs younger, 20 kg lighter, had worse renal function (mean CrCl 64.9 vs. 77.3 mL/min), and higher rates of prior stroke/transient ischemic attack (37.2% vs 26.6%), P&amp;lt;0.001 for each. The median value of time in therapeutic range of patients randomized to warfarin was lower in Asians than non-Asians (57.7% vs. 66.2%, P&amp;lt;0.001). In the warfarin arm, Asians had a higher adjusted risk of stroke/systemic embolic events (SEE), major bleeding (MB), ICH, GI bleeding (GIB), and net clinical outcome (NCO: stroke/SEE, MB, or death)(Figure; Upper panel). Compared to warfarin, SD DOACs significantly reduced the risks of stroke/SEE, MB, and NCO to a greater degree in Asians than non-Asians (HR stroke/SEE: Asians 0.65 vs Non-Asians 0.86; HR MB: Asians 0.62 vs Non-Asians 0.91; HR NCO: Asians 0.76 vs non-Asians 0.94; Pint &amp;lt;0.02 for each), while SD DOACs increased GIB only in non-Asians (Asian HR 0.92 [0.69-1.23] vs Non-Asians HR 1.41 [1.25-1.58], Pint 0.009; Figure Lower panel). Conclusions The adjusted risks of stroke/SEE and major bleeding with warfarin were higher in Asians compared to non-Asians. The benefits of DOACs over warfarin in preventing stroke/SEE, MB, and net clinical outcomes were significantly greater in Asians than non-Asians.

Heart Failure Risk Assessment Using Biomarkers in Patients With Atrial Fibrillation: Analysis From COMBINE-AF

BackgroundHeart failure (HF) is common among patients with atrial fibrillation (AF), and accurate risk assessment is clinically important. ObjectivesThe goal of this study was to investigate the incremental prognostic performance of N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and growth differentiation factor (GDF)-15 for HF risk stratification in patients with AF. MethodsIndividual patient data from 3 large randomized trials comparing direct oral anticoagulants (DOACs) with warfarin (ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48], and RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy]) from the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) cohort were pooled; all patients with available biomarkers at baseline were included. The composite endpoint was hospitalization for HF (HHF) or cardiovascular death (CVD), and secondary endpoints were HHF and HF-related death. Cox regression was used, adjusting for clinical factors, and interbiomarker correlation was addressed using weighted quantile sum regression analysis. ResultsIn 32,041 patients, higher biomarker values were associated with a graded increase in absolute risk for CVD/HHF, HHF, and HF-related death. Adjusting for clinical variables and all biomarkers, NT-proBNP (HR per 1 SD: 1.68; 95% CI: 1.59-1.77), hs-cTnT (HR: 1.39; 95% CI: 1.33-1.44), and GDF-15 (HR: 1.20; 95% CI: 1.15-1.25) were significantly associated with CVD/HHF. The discrimination of the clinical model improved significantly upon addition of the biomarkers (c-index: 0.70 [95% CI: 0.69-0.71] to 0.77 [95% CI: 0.76-0.78]; likelihood ratio test, P < 0.001). Using weighted quantile sum regression analysis, the contribution to risk assessment was similar for NT-proBNP and hs-cTnT for CVD/HHF (38% and 41%, respectively); GDF-15 provided a statistically significant but lesser contribution to risk assessment. Results were similar for HHF and HF-related death, individually, and across key subgroups of patients based on a history of HF, AF pattern, and reduced or preserved left ventricular ejection fraction. ConclusionsNT-proBNP, hs-cTnT, and GDF-15 contributed significantly and independently to the risk stratification for HF endpoints in patients with AF, with hs-cTnT being as important as NT-proBNP for HF risk stratification. Our findings support a possible future use of these biomarkers to distinguish patients with AF at low or high risk for HF.

Computerized clinical decision support to improve stroke prevention therapy in primary care management of atrial fibrillation: a cluster randomized trial

Despite guidelines supporting antithrombotic therapy use in atrial fibrillation (AF), under-prescribing persists. We assessed whether computerized clinical decision support (CDS) would enable guideline-based antithrombotic therapy for AF patients in primary care. This cluster randomized trial of CDS versus usual care (UC) recruited participants from primary care practices across Nova Scotia, following them for 12 months. The CDS tool calculated bleeding and stroke risk scores and provided recommendations for using oral anticoagulants (OAC) per Canadian guidelines. From June 14, 2014 to December 15, 2016, 203 primary care providers (99 UC, 104 CDS) with access to high-speed Internet were recruited, enrolling 1,145 eligible patients (543 UC, 590 CDS) assigned to the same treatment arm as their provider. Patient mean age was 72.3 years; most were male (350, 64.5% UC, 351, 59.5% CDS) and from a rural area (298, 54.9% UC, 315, 53.4% CDS). At baseline, a higher than anticipated proportion of patients were receiving guideline-based OAC therapy (373, 68.7% UC, 442, 74.9% CDS; relative risk [RR] 0.97 (95% confidence interval [CI], 0.87-1.07; P = .511)). At 12 months, prescription data were available for 538 usual care and 570 CDS patients, and significantly more CDS patients were managed according to guidelines (415, 77.1% UC, 479, 84.0% CDS; RR 1.08 (95% CI, 1.01-1.15; P = .024)). Notwithstanding high baseline rates, primary care provider access to the CDS over 12 months further optimized the prescribing of OAC therapy per national guidelines to AF patients potentially eligible to receive it. This suggests that CDS can be effective in improving clinical process of care. Clinical Trials NCT01927367. https://clinicaltrials.gov/ct2/show/NCT01927367?term=NCT01927367&draw=2&rank=1.

Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation.

The efficacy and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain. We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m2 (n=598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m2. Among 58 464 patients, the median BMI was 28.3 (interquartile range, 25.2-32.2) kg/m2, and the median BW was 81.0 (interquartile range, 70.0-94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke/SEE overall (adjusted hazard ratio [HRadj], 0.80 [95% CI, 0.73-0.88]; P<0.001), with a generally consistent effect across BMI (Ptrend across HRs, 0.48). NOACs also reduced major bleeding overall (HRadj, 0.88 [95% CI, 0.82-0.94]; P<0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [Ptrend], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HRadj, 0.91 [95% CI, 0.87-0.95]; P<0.001; death, HRadj, 0.91 [95% CI, 0.86-0.97]; P=0.003), these benefits were attenuated at higher BMI (Ptrend, 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW. The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.

Characteristics of Ischemic Stroke Despite Oral Anticoagulant Use For Atrial Fibrillation.

Oral anticoagulation (OAC) prevents stroke in atrial fibrillation, yet a residual stroke risk remains. In this single-center retrospective analysis of acute ischemic stroke patients despite OAC, suboptimal OAC treatment is common (30%: inappropriate dosing (17%); patient non-adherence (13%)). Other causes of stroke included OAC interruption (14.5%), a competing stroke mechanism (11.0%), and undetermined breakthrough stroke in 44.5%. Overall, easily modifiable causes of ischemic stroke despite OAC are common. Accordingly, strategies to improve treatment compliance, including appropriate dosing along with guideline-based risk factor and periprocedural OAC management, should be emphasized to improve secondary stroke prevention in this patient population.

Abstract 17095: Change in Oral Anticoagulant Use for Atrial Fibrillation From 2013 to 2018 Among US Veterans and the Impact of Frailty

Introduction: Direct oral anticoagulants (DOACs) are superior to warfarin in both efficacy and safety regardless of frailty status. Data on prescribing patterns of different oral anticoagulants (OACs) in frail older adults are limited. Methods: We utilized the Veterans Health Administration clinical data, to identify those aged 65 and older with a diagnosis of non-valvular atrial fibrillation (AF) who initiated anticoagulation in 2013 and 2018. Frailty was assessed using the 31-item VA Frailty Index (VA-FI). Patients were stratified into 3 categories. VA-FI: frail (frailty index &gt;0.2), pre-frail (frailty index 0.11-0.2), and non-frail (frailty index 0-0.1). Baseline data on prior stroke, CHA 2 DS 2 -VASc score, and bleeding were extracted. Descriptive statistics and logistic regression were used to examine association of frailty with choice of OAC. Results: Among 39,647 Veterans included from 2013 and 2018, mean age was between 71 to 76. 99% were male and 88% white race. From 2013 to 2018, DOACs use increased from 21% to 88%, while warfarin use decreased accordingly. Among the OACs, dabigatran was dominant (65%) in 2013 but apixaban was dominant (66%) in 2018. Increasing frailty was associated with reduced use of DOACs (p&lt;0.001 in 2013 and 2018). Regardless of the choice of drug, the prior bleeding and prior stroke/transient ischemic attack were mostly seen in the frail population ranging between 54-60% and 20-21% respectively. CHA 2 DS 2 -VASc score averaged 3 for non-frail, and 4 for prefrail and frail patients regardless of the year. (Figure) Conclusion: Prior bleeding and stroke episodes were more common among the frail population. There was significant reduction in use of DOACs in both years with increasing frailty. Studying the impact of anticoagulant choice on clinical outcomes among frail older adults with non-valvular AF are needed.

Abstract 16362: Does Extra-Pulmonary Triggers or Autonomic Neural Activity Affect the Rhythm Control by Anti-Arrhythmic Drugs in Patients With Post-Ablation Atrial Fibrillation Recurrence?

Introduction: Although the EAST-AFNET trial demonstrated the usefulness of atrial fibrillation (AF) rhythm control, including antiarrhythmic drugs (AADs), little is known about their effect on recurred AF after catheter ablation (CA). Hypothesis: We explored the effect of AADs depending on the presence of extra-pulmonary vein triggers (ExPVT) or post-ablation heart rate variability (HRV) in patients who recurred after AFCA. Methods: In this retrospective analysis of a single-center cohort, we analyzed 2,036 patients who underwent de-novo AFCA, and 486 of them had recurrent AF and subsequently underwent rhythm control with AADs. We investigated the effects of the extra-pulmonary vein (PV) triggers and post-procedural 3 rd month HRV (rMSSD; cut-off determined by Youden index) on the AAD responsiveness. Results: The post-AFCA recurrence was significantly higher in patients with ExPVT (Log-rank p&lt;0.001, HR 1.45 [1.16-1.83], p=0.001) or higher 3 rd month post procedure HRV-rMSSD (Log-rank p&lt;0.001, HR 1.36 [1.11-1.65], p=0.003) than their counterparts. Patients with ExPVT at de novo procedure had significantly higher 3 rd month rMSSD (15.0 [11.0-23.0] vs. 17.0 [11.0-28.0], p=0.022) and patients with high 3 rd month rMSSD showed a higher rate of ExPVT identified at the 2 nd repeat procedure (n=160, 41.0% vs. 22.2%, p=0.019). Among those patients how recurred AF after AFCA, post-AAD recurrence did not differ depending on ExPVT (Log-rank p=0.455, HR 1.12 [0.78-1.69], p=0.436) or rMSSD (Log-rank p=0.457, HR 1.16 [0.87-1.55], p=0.300). Post-AAD recurrence did not differ between class IC and III AADs (p for interaction = 0.311). Conclusion: ExPVT and post-procedural high rMSSD are independent risk factors for post-AFCA recurrences but not for AAD response in recurred AF patients. Whether AADs may suppress ExPVT and modulate cardiac autonomic activity after post-AFCA recurrences need further investigation.

Sex Differences in High-Cost Users of Healthcare for Atrial Fibrillation

BackgroundHealthcare resource use for atrial fibrillation (AF) is high, but it may not be equivalent across all patients. We examined whether sex differences exist for AF high-cost users (HCUs), who account for the top 10% of total acute care costs. MethodsAll patients aged ≥ 20 years who presented to the emergency department (ED) or were hospitalized with AF were identified in Alberta, Canada, between 2011 and 2015. The cohort was categorized by sex into HCUs and non-HCUs. Healthcare utilization was defined as ED, hospital, and physician visits, and costs included those for hospitalization, ambulatory care, physician billing, and drugs. All costs were inflated to 2022 Canadian dollars (CAD$). ResultsAmong 48,030 AF patients, 45.1% were female. Of these, 31.8% were HCUs, and the proportions of female and male patients were equal (31.9% vs 31.7%). Female HCUs were older, more likely to have hypertension and heart failure, and had a higher stroke risk than male HCUs. Mean healthcare utilization did not differ among HCUs by sex, except for number of ED visits, which was higher in male patients (12.7% vs 9.2%, P < 0.0001). Overall, HCUs accounted for 65.8% of the total costs (CAD$3.4 billion). Almost half of total HCU costs were attributable to female HCUs (CAD$966.1 million). Significant differences were present in the distributions of HCU-related costs (male patients: 74.6% hospitalization, 9.5% ambulatory care, 12.4% physician billing, 3.5% drugs; female patients: 77.7% hospitalization, 7.4% ambulatory care, 11.5% physician billing, 3.5% drugs, P < 0.0001). ConclusionsDespite having a lower AF prevalence, female patients represent an equal proportion of HCUs, and account for almost half the total HCU costs. Interventions targeted at reducing the number of AF HCU are needed, particularly for female patients.

Development and Validation of the DOAC Score: A Novel Bleeding Risk Prediction Tool for Patients With Atrial Fibrillation on Direct-Acting Oral Anticoagulants.

Current clinical decision tools for assessing bleeding risk in individuals with atrial fibrillation (AF) have limited performance and were developed for individuals treated with warfarin. This study develops and validates a clinical risk score to personalize estimates of bleeding risk for individuals with atrial fibrillation taking direct-acting oral anticoagulants (DOACs). Among individuals taking dabigatran 150 mg twice per day from 44 countries and 951 centers in this secondary analysis of the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy), a risk score was developed to determine the comparative risk for bleeding on the basis of covariates derived in a Cox proportional hazards model. The risk prediction model was internally validated with bootstrapping. The model was then further developed in the GARFIELD-AF registry (Global Anticoagulant Registry in the Field-Atrial Fibrillation), with individuals taking dabigatran, edoxaban, rivaroxaban, and apixaban. To determine generalizability in external cohorts and among individuals on different DOACs, the risk prediction model was validated in the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) pooled clinical trial cohort and the Quebec Régie de l'Assurance Maladie du Québec and Med-Echo Administrative Databases (RAMQ) administrative database. The primary outcome was major bleeding. The risk score, termed the DOAC Score, was compared with the HAS-BLED score. Of the 5684 patients in RE-LY, 386 (6.8%) experienced a major bleeding event, within a median follow-up of 1.74 years. The prediction model had an optimism-corrected C statistic of 0.73 after internal validation with bootstrapping and was well-calibrated based on visual inspection of calibration plots (goodness-of-fit P=0.57). The DOAC Score assigned points for age, creatinine clearance/glomerular filtration rate, underweight status, stroke/transient ischemic attack/embolism history, diabetes, hypertension, antiplatelet use, nonsteroidal anti-inflammatory use, liver disease, and bleeding history, with each additional point scored associated with a 48.7% (95% CI, 38.9%-59.3%; P<0.001) increase in major bleeding in RE-LY. The score had superior performance to the HAS-BLED score in RE-LY (C statistic, 0.73 versus 0.60; P for difference <0.001) and among 12 296 individuals in GARFIELD-AF (C statistic, 0.71 versus 0.66; P for difference = 0.025). The DOAC Score had stronger predictive performance than the HAS-BLED score in both validation cohorts, including 25 586 individuals in COMBINE-AF (C statistic, 0.67 versus 0.63; P for difference <0.001) and 11 945 individuals in RAMQ (C statistic, 0.65 versus 0.58; P for difference <0.001). In individuals with atrial fibrillation potentially eligible for DOAC therapy, the DOAC Score can help stratify patients on the basis of expected bleeding risk.

Safety and Efficacy of Novel Oral Anticoagulants as Compared to Warfarin in Treatment of Atrial Fibrillation

BACKGROUND - Novel oral anticoagulants (NOACs) are a class of medications used to prevent blood clots thereby various studies have demonstrated their potential benefit in their use in atrial fibrillation. They act by inhibiting clotting factors such as factor Xa or Thrombin. Unlike traditional anticoagulants like Vitamin K antagonist (Warfarin), NOACs have a more predictable effect and require less frequent monitoring. OBJECTIVE – We aim to explore the safety and efficacy of Novel oral anticoagulants as compared to warfarin in the treatment of atrial fibrillation. Additionally, a comparative analysis among NOACs was conducted to determine the most superior among them. METHODS – We performed a pairwise systematic review in patients with atrial fibrillation undergoing anticoagulation with the help of NOAC as compared to those undergoing anticoagulation on Warfarin by analyzing various electronic databases from 2005 till 2023 and filtered 11 studies having 70,801 sample size distributed comparably among the two groups based on our inclusion criteria. RESULTS – There was a slight difference between the safety and efficacy of the NOAC and Warfarin groups. Among the participants, 3019 individuals (8.93%) who were administered Warfarin experienced major bleeding complications, in contrast to 2690 participants (7.26%) who were on NOACs. Regarding the occurrence of stroke, the Warfarin group observed a rate of 987 cases (2.92%), while the NOAC group had 1119 instances (3.02%) of stroke. CONCLUSION – The results of recent NOACs studies emphasizes on the superiority of them as compared to warfarin in both rapid onset of action as well as better patient compliance. Our review suggests a lower risk of bleeding but a slightly higher risk of stroke occurrence in NOACs as compared to the Warfarin group, thereby showing their superiority in clinical utility, though more robust clinical trials are required to establish long-term benefits.

Anticoagulant Use in Atrial Fibrillation in a Regional Teaching Hospital

Anticoagulant Use in Atrial Fibrillation in a Regional Teaching Hospital

Retrospective Cross-sectional Analysis of Older Adults Living with Frailty and Anticoagulant Use for Atrial Fibrillation.

Oral anticoagulation (OAC) is recommended for most individuals with atrial fibrillation (AF), including those who are frail. Based on previous literature, those who are frail may be less likely to be prescribed OAC, and up to one-third may receive an inappropriate dose if prescribed a direct oral anticoagulant (DOAC). The objectives of this study were to determine the proportion of frail ambulatory older adults with AF who are prescribed OAC, compare the rates of OAC use across the frailty spectrum, assess the appropriateness of DOAC dosing, and identify if frailty and geriatric syndromes impact OAC prescribing patterns. Retrospective cross-sectional review of individuals with AF referred to an ambulatory clinic for older adults living with frailty and/or geriatric syndromes. Rockwood clinical frailty score of ≥4 was used to define frailty and DOAC appropriateness was assessed based on the Canadian Cardiovascular Society AF guidelines. Two hundred and ten participants were included. The mean age was 84 years, 49% were female and the median frailty score was 5. Of the 185 participants who were frail, 82% were prescribed an OAC (83% with frailty score of 4, 85% with a frailty score of 5, and 78% with a frailty score of 6). Of those prescribed a DOAC, 70% received a guideline-approved dose. Over 80% of ambulatory older adults with frailty and AF were prescribed an OAC. However, of those prescribed a DOAC, 30% received an unapproved dose, suggesting more emphasis should be placed on initial and ongoing dosage selection.

Direct Oral Anticoagulants Versus Warfarin Across the Spectrum of Kidney Function: Patient-Level Network Meta-Analyses From COMBINE AF.

There is uncertainty surrounding the use of direct oral anticoagulants (DOACs) in patients with kidney dysfunction. Using the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database (data from RE-LY [Randomized Evaluation of Long-term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), we performed an individual patient-level network meta-analysis to evaluate the safety and efficacy of DOACs versus warfarin across continuous creatinine clearance (CrCl). A multivariable Cox model including treatment-by-CrCl interaction with random effects was fitted to estimate hazard ratios for paired treatment strategies (standard-dose DOAC, lower-dose DOAC, and warfarin). Outcomes included stroke and systemic embolism (S/SE), major bleeding, intracranial hemorrhage (ICH), and death. Among 71 683 patients (mean age, 70.6±9.4 years; 37.3% female; median follow-up, 23.1 months), the mean CrCl was 75.5±30.5 mL/min. The incidence of S/SE, major bleeding, ICH, and death increased significantly with worsening kidney function. Across continuous CrCl values down to 25 mL/min, the hazard of major bleeding did not change for patients randomized to standard-dose DOACs compared with those randomized to warfarin (Pinteraction=0.61). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of ICH at CrCl values <122 mL/min, with a trend for increased safety with DOAC as CrCl decreased (6.2% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Compared with warfarin, standard-dose DOAC use resulted in a significantly lower hazard of S/SE with CrCl <87 mL/min, with a significant treatment-by-CrCl effect (4.8% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.01). The hazard of death was significantly lower with standard-dose DOACs for patients with CrCl <77 mL/min, with a trend toward increasing benefit with lower CrCl (2.1% decrease in hazard ratio per 10-mL/min decrease in CrCl; Pinteraction=0.08). Use of lower-dose rather than standard-dose DOACs was not associated with a significant difference in incident bleeding or ICH in patients with reduced kidney function but was associated with a higher incidence4 of death and S/SE. Standard-dose DOACs are safer and more effective than warfarin down to a CrCl of at least 25 mL/min. Lower-dose DOACs do not significantly lower the incidence of bleeding or ICH compared with standard-dose DOACs but are associated with a higher incidence of S/SE and death. These findings support the use of standard-dose DOACs over warfarin in patients with kidney dysfunction.

Evaluation of outcomes with apixaban use for venous thromboembolism in hospitalized patients with end-stage renal disease receiving renal replacement therapy.

While direct oral anticoagulants (DOACs) received expanded labeling for use in atrial fibrillation (AF) for end-stage renal disease (ESRD) based on pharmacokinetic trials, little data exist regarding the use of DOACs for venous thromboembolism (VTE) in ESRD patients requiring renal replacement therapy (RRT). This retrospective, descriptive cohort study evaluated adult patients with a diagnosis of ESRD on RRT and with a VTE diagnosis receiving apixaban therapy prior to or during admission. The primary outcome was to identify major bleeding events within 72h of last apixaban dose administration. Secondary outcomes included new VTE while on apixaban, appropriateness of anticoagulation regimen with regards to FDA labeled dosing and frequency, anticoagulation regimen adjustments, and factor Xa inhibitor-specific anti-Xa levels if available. A total of 68 patients met criteria for inclusion in the final analysis. Major bleeding events occurred in 13.2% of patients receiving apixaban within the last 72h. Recurrent thrombosis occurred in 7.4% of patients. The use of apixaban for VTE in patients with ESRD on RRT led to a higher risk of bleeding compared to that of landmark trials. Therefore, apixaban use should occur following shared decision making especially if there is no contraindication to warfarin.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin Among Obese Patients With Atrial Fibrillation

BackgroundObese patients are underrepresented in clinical trials assessing the comparative effectiveness and safety of use of direct oral anticoagulants vs use in atrial fibrillation (AF) patients. MethodsUsing data from Quebec provincial administrative databases, for the years2010-2017, we created a retrospective cohort of patients with inpatient or outpatient coding for AF and obesity who were newly prescribed an oral anticoagulant. The primary safety outcome was a composite of intracranial, gastrointestinal, and major bleeding from other sites, and the primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, acute myocardial infarction, and death in the first year after oral anticoagulant initiation. Treatment groups were compared using inverse-probability-of-treatment-weighting Cox proportional-hazards models. ResultsA total of 2263 patients were included, of whom 1253, 403, and 539 filled a warfarin, standard-dose rivaroxaban, and standard-dose apixaban prescription, respectively. Standard-dose rivaroxaban was associated with a similar composite safety (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.44-1.91) and composite effectiveness risk (HR 1.42; 95% CI 0.99-2.04) compared to warfarin, whereas standard-dose apixaban was associated with a lower composite safety (HR 0.40; 95% CI 0.16-0.98) and similar composite effectiveness risk (HR 0.96; 95% CI 0.67-1.39). ConclusionUse of direct oral anticoagulants in obese AF patients was associated with a similar effectiveness and safety profile to that of warfarin use.

Apixaban and rivaroxaban use for atrial fibrillation in patients with obesity and BMI ≥50kg/m2.

Apixaban and rivaroxaban are increasingly used for thromboembolism prophylaxis in patients with non-valvular atrial fibrillation (NVAF) and commonly in patients with obesity and body mass index (BMI) ≥50kg/m2 despite the limited data. This study aimed to establish the effectiveness and safety of apixaban and rivaroxaban in patients with NVAF and BMI ≥50kg/m2 . A single health-system, retrospective cohort study evaluated the effectiveness and safety of apixaban and rivaroxaban initiated in adult patients (≥18years of age) with BMI ≥50kg/m2 and NVAF. Outcomes of ischemic stroke, systemic embolic events, and bleeding were compared to a cohort of patients with BMI 18 to 30kg/m2 . After 1619 patient-years worth of follow-up in 595 patients, the primary endpoint of incidence of ischemic stroke was numerically similar in both groups, 1.3 per 100 patient-years in the BMI ≥50kg/m2 group, compared to 2.0 per 100 patient-years in the BMI <30kg/m2 group (RR 0.65, 95% CI 0.38-1.82, p=0.544). Incidence of major bleeding and clinically relevant non-major bleeding was also numerically similar between the two groups. This study demonstrated that apixaban and rivaroxaban in patients with a BMI ≥50kg/m2 for treatment of NVAF may be safe and effective at preventing thromboembolic events and had no increased risk of bleeding. Although, findings should be interpreted with caution and confirmed with additional studies. This study contributes to the growing body of evidence that direct oral anticoagulants (DOACs) may be effective and safe to use for the treatment of NVAF in patients with BMI ≥50kg/m2 .

Abstract 11742: Knowledge on Anticoagulation Use in Atrial Fibrillation With Left Atrial Appendage Thrombus Among Medicine Residents

Introduction: Left atrial appendage (LAA) thrombus increases thromboembolic risk in patients with atrial fibrillation (AF). Importantly, 40% of LAA thrombus patients will have an inadequate response to anticoagulation during follow-up. Of note, these patients are frequently followed by medicine residents in the clinic. Therefore, we aimed to explore residents' knowledge on anticoagulation use for the treatment of LAA thrombus. Hypothesis: Insufficient knowledge on anticoagulation for the treatment of LAA thrombus could contribute to inadequate treatment response during patients' follow-up. Methods: All medicine residents (n=96) at Rutgers University New Jersey Medical School were emailed a 26-question survey on the indication, dosing, pharmacokinetics and clinical experience using direct oral anticoagulants (DOACs) and vitamin-K-antagonists (VKA) in AF patients with LAA thrombus. Results: Of 62 responders, 42 (68%) have been prescribing DOACs in the clinic with apixaban being most commonly prescribed. Thirty-seven (61%) indicated DOACs as the first-line agents for LAA thrombus whereas 24 (39%) chose VKA. Nineteen (33%) responders indicated apixaban dosing correctly, and 51 (84%) indicated appropriately relation of apixaban with meals. If follow-up imaging reconfirmed LAA thrombus, 54 (89%) would switch to VKA whereas 7 (11%) would use other DOACs. Nineteen (32%) responders indicated rivaroxaban dosing correctly and only 10 (16%) indicated appropriately how to administer rivaroxaban with meals. If follow-up imaging reconfirmed LAA thrombus, 43 (71%) would switch to VKA whereas 18 (29%) would use other DOACs. Forty-one (72%) responders indicated dabigatran dosing correctly and 36 (58%) indicated no relation to food intake. If follow-up imaging reconfirmed LAA thrombus, 40 (65%) responders would switch to VKA whereas 22 (35%) would use other DOACs. For VKA, 51 (88%) indicated therapeutic INR range of 2-3 and 7 (12%) chose 2.5-3.5. If follow-up imaging reconfirmed LAA thrombus, 38 (61%) would increase INR goal whereas 24 (39%) would switch to DOACs. Conclusions: This survey identified knowledge gaps in dosing and pharmacokinetics of DOACs among medicine residents despite being more likely to prescribe DOACs over VKA to treat LAA thrombus.

Abstract 12118: Patterns of Anticoagulation Use in Atrial Fibrillation and Active Cancer: Observations From Medicare

Introduction: Use of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and cancer is challenging due to increased thrombotic and bleeding risks, and data on prescription patterns are lacking. Hypothesis: Underutilization of OAC among patients with AF and cancer is associated with cancer specific factors. Methods: This study examined OAC use and factors associated with discontinuation of OAC among Medicare patients with AF and a new diagnosis of cancer from 2011-2016. We described OAC use patterns prior to and after a diagnosis of cancer. Logistic regression was used to evaluate clinical variables associated with discontinuation of OAC at time of cancer diagnosis and cox proportional hazards model was used to evaluate variables associated with discontinuation after diagnosis. Results: Among 44,769 patients with established AF and newly diagnosed cancer, 30.2% (n=13,508) were taking OAC at the time of cancer diagnosis. A total of 15,228 patients (34%) had an OAC prescription fill after index cancer diagnosis. Warfarin was the most commonly used OAC, but direct oral anticoagulant use increased over the study period. A total of 29.5% of patients had their OAC discontinued at the time of cancer diagnosis. Patients with gastric (OR 2.75, CI 2.12-3.57), pancreatic (OR 2.71, CI 2.15-3.41), and colorectal (OR 1.97, CI 1.70-2.28) cancer were most likely to have their OAC discontinued at diagnosis (Figure). Bleeding (HR1.37, CI 1.28-1.48) and chemotherapy (HR 1.38, CI 1.06-1.80) were associated with subsequent discontinuation in those who remained on OAC after diagnosis. Conclusions: Nearly 2 in 3 patients with established AF were not treated with OAC after cancer diagnosis despite an elevated stroke risk. Significant heterogeneity in OAC use exists depending on cancer type, baseline comorbidities, and chemotherapy use. Studies are needed to characterize the thrombotic and bleeding risks in this population to establish management guidelines.

A Systematic Review of Economic Aspects of Service Interventions to Increase Anticoagulation Use in Atrial Fibrillation.

To systematically identify and appraise existing evidence surrounding economic aspects of anticoagulation service interventions for patients with atrial fibrillation. We searched the published and grey literature up to October 2019 to identify relevant economic evidence in any health care setting. A narrative-synthesis approach was taken to summarise evidence by economic design and type of service intervention, with costs expressed in pound sterling and valued at 2017 to 2018 prices. A total of 13 studies met our inclusion criteria from 1,168 papers originally identified. Categories of interventions included anticoagulation clinics (n = 4), complex interventions (n = 4), decision support tools (n = 3) and patient-centred approaches (n = 2). Anticoagulation clinics were cost-saving compared with usual care (range for mean cost difference: £188-£691 per-patient per-year) with equivalent health outcomes. Only one economic evaluation of a complex intervention was conducted; case management was more expensive than usual care (mean cost difference: £255 per-patient per-year) and the probability of its cost-effectiveness did not exceed 70%. There was limited economic evidence surrounding decision support tools or patient-centred approaches. Targeting service interventions at high-risk groups and those with suboptimal treatment was most likely to result in cost savings. This review revealed some evidence to support the cost-effectiveness of anticoagulation clinics. However, summative conclusions are constrained by a paucity of economic evidence, a lack of direct comparisons between interventions, and study heterogeneity in terms of intervention, comparator and study year. Further research is urgently needed to inform commissioning and service development. Data from this review can inform future economic evaluations of anticoagulation service interventions.