Publications by authors named "Jack Ansell"

153 Publications

Ciraparantag, an anticoagulant reversal drug: mechanism of action, pharmacokinetics, and reversal of anticoagulants.

Blood 2021 01;137(1):115-125

Perosphere Technologies Inc, Danbury, CT.

Ciraparantag, an anticoagulant reversal agent, is a small molecule specifically designed to bind noncovalently by charge-charge interaction to unfractionated heparin and low-molecular-weight heparin. It shows binding characteristics that are similar to those of direct oral anticoagulants (DOACs). A dynamic light-scattering methodology was used to demonstrate ciraparantag's binding to the heparins and DOACs and its lack of binding to a variety of proteins including coagulation factors and commonly used drugs. Ciraparantag reaches maximum concentration within minutes after IV administration with a half-life of 12 to 19 minutes. It is primarily hydrolyzed by serum peptidases into 2 metabolites, neither of which has substantial activity. Ciraparantag and its metabolites are recovered almost entirely in the urine. In animal models of bleeding (rat tail transection and liver laceration), a single IV dose of ciraparantag given at peak concentrations of the anticoagulant, but before the bleeding injury, significantly reduced the blood loss. Ciraparantag, given after the bleeding injury, also significantly reduced blood loss. It appears to have substantial ability to reduce blood loss in animal models in which a variety of anticoagulants are used and has potential as a useful DOAC reversal agent.
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http://dx.doi.org/10.1182/blood.2020007116DOI Listing
January 2021

Discontinuation rates of warfarin versus direct acting oral anticoagulants in US clinical practice: Results from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II (ORBIT-AF II).

Am Heart J 2020 08 28;226:85-93. Epub 2020 Apr 28.

Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.

While oral anticoagulation is a cornerstone of stroke prevention therapy in atrial fibrillation (AF), few studies have evaluated comparative discontinuation rates in clinical practice. The objective of this study is to evaluate discontinuation rates among patients on warfarin and direct oral anticoagulants (DOACs) in clinical practice.

Methods: The ORBIT-AF II Registry enrolled 10,005 total AF patients with a CHADSVASc score of ≥2 on warfarin or DOACs from 235 clinical practices across the US from February 13, 2013 and July 12, 2017. Descriptive statistics and multivariable Cox regression modeling were used to describe baseline characteristics and predictors of discontinuation. Unadjusted and adjusted discontinuation rates and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and propensity score adjustment, respectively.

Results: At baseline, 16.4% (N = 1642/10,005) were treated with warfarin, 83.6% (N = 8363/10,005) with DOACs and 1498/10,005 patients (15.0%) discontinued therapy [warfarin = 236/1642 (14.4%) vs DOACs = 1262/8363 (15.1%)]. At 6 and 12 months respectively, among 7049 patients with a new diagnosis of AF within 6 months, adjusted discontinuation rates for warfarin versus DOACs were as follows: [6 months: 7.9%, 95%CI (6.8%-9.0%) vs 9.6% (8.4%-10.7%), P = .16]; [12 months: 12.7% (11.0%-14.3%) vs 15.3% (13.6%-16.9%), P = .02)]. Patients who discontinued therapy with warfarin or DOACs had higher risk of adverse clinical outcomes including: all-cause mortality and cardiovascular death (CV) than those who continued treatment.

Conclusion: In a community based AF cohort, adjusted rates of discontinuation at 12-months were higher in DOAC-treated versus VKA-treated patients. Discontinuation of oral anticoagulation was associated with increased absolute risk of all-cause mortality and CV death.

Clinical Trial Registration: URL:https://clinicaltrials.gov. Unique Identifier: NCT01701817.
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http://dx.doi.org/10.1016/j.ahj.2020.04.016DOI Listing
August 2020

Outcomes of Cardiac Catheterization in Patients With Atrial Fibrillation on Anticoagulation in Contemporary in Practice: An Analysis of the ORBIT II Registry.

Circ Cardiovasc Interv 2020 05 15;13(5):e008274. Epub 2020 May 15.

Duke Clinical Research Institute, Durham, NC (J.P.P., D.N.H., R.B., E.D.P., S.V.R.).

Background: Patients with atrial fibrillation on oral anticoagulation (OAC) undergoing cardiac catheterization face risks for embolic and bleeding events, yet information on strategies to mitigate these risks in contemporary practice is lacking.

Methods: We aimed to describe the clinical/procedural characteristics of a contemporary cohort of patients with atrial fibrillation on OAC who underwent cardiac catheterization. Use of bleeding avoidance strategies and bridging therapy were described and outcomes including death, stroke, and major bleeding at 30 days and 1 year were compared by OAC type.

Results: Of 13 404 patients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II Registry from 2013 to 2016, 741 underwent cardiac catheterization (139 with percutaneous coronary intervention) in the setting of OAC. The patients' median age was 71, 61.8% were male, white (87.2%), had hypertension (83.7%), hyperlipidemia (72.1%), diabetes mellitus (31.6%), and chronic kidney disease (28.2%); 20.2% received warfarin while 79.8% received direct acting oral anticoagulant. One third of patients underwent radial artery access, and bivalirudin was used in 4.6%. Bridging therapy was used more often in patients on warfarin versus direct acting oral anticoagulant (16.7% versus10.0%). OAC was interrupted in 93.8% of patients. Patients on warfarin versus direct acting oral anticoagulant were equally likely to restart OAC (58.0% versus 60.7%), had similar use of antiplatelet therapy (44.0% versus 41.3%) after catheterization, and had similar rates of myocardial infarction and death at 1 year, but higher rates of major bleeding (43.3 versus 12.9 events/100 patient years) and stroke (4.9 versus 1.9 events/100 patient years).

Conclusions: In a real-world registry of patients with atrial fibrillation undergoing cardiac catheterization, most cases are elective, performed by femoral access, with interruption of OAC. Bleeding avoidance strategies such as radial artery access and bivalirudin were used infrequently and use of bridging therapy was uncommon. Nearly 40% of patients did not restart OAC postprocedure, exposing patients to risk for stroke. Further research is necessary to optimize the management of patients with atrial fibrillation undergoing cardiac catheterization.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.119.008274DOI Listing
May 2020

A systematic review and meta-analysis of supplemental education in patients treated with oral anticoagulation.

Blood Adv 2019 05;3(10):1638-1646

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

Oral anticoagulants (OACs) are indicated for treatment and prevention of thromboembolic diseases. Supplemental patient education (education) has been proposed to improve outcomes, and this systematic review assesses the effect of education on mortality, thromboembolic events (TEEs) including venous thromboembolism (VTE), and bleeding in patients taking OACs. Randomized controlled trials were included, and 2 authors independently screened articles and assessed risk of bias. In 9 trials (controls, n = 720; intervention group patients, n = 646), 4 assessed critical outcomes of mortality, TEEs (VTE, stroke, and systemic embolism), and bleeding to estimate absolute risk ratios. When comparing education with usual care, in 1000 patients, there may be 12 fewer deaths (95% confidence interval [CI], 19 fewer to 154 more) and 16 fewer bleeding events (95% CI, 34 fewer to 135 more), but this evidence is uncertain; the evidence also suggests 6 fewer VTEs (95% CI, 10 fewer to 16 more) and 8 fewer TEEs (95% CI, 16 fewer to 18 more). The mean difference in time in therapeutic range may be 2.4% higher in the education group compared with usual care (95% CI, 2.79% lower to 7.58% higher). We also found very low certainty of evidence for a large increase in knowledge scores (standardized mean difference, 0.84 standard deviation units higher; 95% CI, 0.51-1.16). Overall, the certainty of evidence was low to very low because of serious risk of bias and serious imprecision. Additional sufficiently powered trials or different approaches to education are required to better assess supplemental education effects on outcomes in patients taking OACs.
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http://dx.doi.org/10.1182/bloodadvances.2019000067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538874PMC
May 2019

Comparison of Patient-Reported Care Satisfaction, Quality of Warfarin Therapy, and Outcomes of Atrial Fibrillation: Findings From the ORBIT - AF Registry.

J Am Heart Assoc 2019 05;8(9):e011205

1 Stanford Center for Clinical Research Stanford University School of Medicine Stanford CA.

Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes among patients with atrial fibrillation ( AF ). Methods and Results Using data from the ORBIT - AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, patients were identified with AF who were taking warfarin and had completed an Anti-Clot Treatment Scale ( ACTS ) questionnaire, a validated metric of patient-reported burden and benefit of oral anticoagulation. Multivariate regressions were used to determine association of ACTS burden and benefit scores with time in therapeutic international normalized ratio range ( TTR ; both ≥75% and ≥60%), warfarin discontinuation, and clinical outcomes (death, stroke, major bleed, and all-cause hospitalization). Among 1514 patients with AF on warfarin therapy (75±10 years; 42% women; CHA DS - VAS c 3.9±1.7), those most burdened with warfarin therapy were younger and more likely to be women, have paroxysmal AF , and to be treated with antiarrhythmic drugs. After adjustment for covariates, ACTS burden scores were independent of TTR ( TTR ≥75%: odds ratio, 1.01 [95% CI , 0.99-1.03]; TTR ≥60%: odds ratio, 1.01 [95% CI , 0.98-1.05]), warfarin discontinuation (odds ratio, 0.99; 95% CI , 0.97-1.01), or clinical outcomes. ACTS benefit scores were also not associated with TTR , warfarin discontinuation, or clinical outcomes. Conclusions In a large registry of patients with AF taking warfarin, ACTS scores provided independent information beyond other traditional metrics of oral anticoagulation care quality and identified patient groups at high risk for dissatisfaction with warfarin therapy.
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http://dx.doi.org/10.1161/JAHA.118.011205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512133PMC
May 2019

Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum.

Am J Hematol 2019 06 16;94(6):697-709. Epub 2019 Apr 16.

Division of Hospital Medicine, Henry Ford Hospital, Detroit, Michigan.

Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non-specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.
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http://dx.doi.org/10.1002/ajh.25475DOI Listing
June 2019

Association of frailty and cognitive impairment with benefits of oral anticoagulation in patients with atrial fibrillation.

Am Heart J 2019 05 30;211:77-89. Epub 2019 Jan 30.

Department of Cardiology, Mayo Clinic, Rochester, MN.

Background: The incidence of cognitive impairment and frailty increase with age and may impact both therapy and outcomes in atrial fibrillation (AF).

Methods: We examined the prevalence of clinically recognized cognitive impairment and frailty (as defined by the American Geriatric Society Criteria) in the Outcomes Registry for Better Informed Care in AF (ORBIT AF) and associated adjusted outcomes via multivariable Cox regression. The interaction between cognitive impairment and frailty and oral anticoagulation (OAC) in determining outcomes was examined.

Results: Among 9749 patients with AF [median (IQR) age 75 (67-82) y, 57% male], cognitive impairment and frailty was identified in 293 (3.0%) and 575 (5.9%) patients respectively. Frail patients (68 vs 77%, P < .001) and those with cognitive impairment (70 vs 77%, P = .006) were both less likely to receive an OAC. Both cognitive impairment [HR (95% CI) 1.34 (1.05-1.72), P = .0198] and frailty [HR 1.29 (1.08-1.55), P = .0060] were associated with increased risk of death. Cognitive impairment and frailty were not associated with stroke/transient ischemic attack (TIA) or major bleeding. In multivariable analysis, there was no interaction between OAC use and cognitive impairment or frailty in their associations with mortality, major bleeding and a composite end point of stroke, non-central nervous system systemic embolism, TIA, myocardial infarction or cardiovascular death.

Conclusion: Those with cognitive impairment or frailty in AF had higher predicted risk for stroke and higher observed mortality, yet were less likely to be treated with OAC. Despite this, the benefits of OAC were similar in patients with and without cognitive impairment or frailty.
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http://dx.doi.org/10.1016/j.ahj.2019.01.005DOI Listing
May 2019

Vitamin K for reversal of excessive vitamin K antagonist anticoagulation: a systematic review and meta-analysis.

Blood Adv 2019 03;3(5):789-796

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of administering vitamin K in patients receiving VKA therapy with INR between 4.5 and 10 and without bleeding. Medline, Embase, and Cochrane databases were searched for relevant randomized controlled trials in April 2018. Search strategy included terms vitamin K administration and VKA-related terms. Reference lists of relevant studies were reviewed, and experts in the field were contacted for relevant papers. Two investigators independently screened and collected data. Risk ratios (RRs) were calculated, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Six studies (1074 participants) were included in the review and meta-analyses. Pooled estimates indicate a nonsignificant increased risk of mortality (RR = 1.42; 95% confidence interval [CI], 0.62-2.47), bleeding (RR = 2.24; 95% CI, 0.81-7.27), and thromboembolism (RR = 1.29; 95% CI, 0.35-4.78) for vitamin K administration, with moderate certainty of the evidence resulting from serious imprecision as CIs included potential for benefit and harm. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR (1.95; 95% CI, 0.88-4.33), with very low certainty of the evidence resulting from serious risk of bias, inconsistency, and imprecision. Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation.
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http://dx.doi.org/10.1182/bloodadvances.2018025163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418499PMC
March 2019

A Novel Whole Blood Point-of-Care Coagulometer to Measure the Effect of Direct Oral Anticoagulants and Heparins.

Semin Thromb Hemost 2019 Apr 19;45(3):259-263. Epub 2018 Dec 19.

Perosphere Technologies, Inc., Danbury, Connecticut.

The direct oral anticoagulants (DOACs) currently require no monitoring for routine therapy of atrial fibrillation or venous thromboembolism. Measurement of activity, however, may be important in patients with major and life-threatening bleeding, patients needing emergent surgery, in reversal situations, or in patients at high risk of bleeding or thrombosis due to underlying conditions. For these patients, a widely available and rapid turnaround assay would be optimal. To date, there is no such assay available, especially for the direct factor Xa inhibitors. This report describes the performance of a new, rapid turnaround, point-of-care (PoC) assay for measuring the activity of a range of anticoagulants, including DOACs and heparins, in emergency situations and for routine measurement in high-risk patients. Perosphere Technologies' PoC coagulometer is a handheld instrument that performs individual coagulation tests on samples of fresh whole blood (∼10 µL) with clotting activated by glass contact and endpoint determination performed by infrared spectroscopy. In preclinical studies using rats anticoagulated with therapeutic doses of edoxaban or enoxaparin, the PoC coagulometer showed a strong linear correlation between pharmacokinetic parameters and clotting time with edoxaban ( = 0.994) and with enoxaparin ( = 0.967). These preclinical results suggest that this PoC coagulometer would be ideal to assess the pharmacodynamic effects of anticoagulants and their reversal agents. The PoC bedside instrument delivers results within minutes and requires no more than a drop of whole blood. Studies are underway to confirm these results in humans and to further characterize the performance of the instrument.
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http://dx.doi.org/10.1055/s-0038-1676317DOI Listing
April 2019

American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy.

Blood Adv 2018 11;2(22):3257-3291

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.

Background: Clinicians confront numerous practical issues in optimizing the use of anticoagulants to treat venous thromboembolism (VTE).

Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in their decisions about the use of anticoagulants in the management of VTE. These guidelines assume the choice of anticoagulant has already been made.

Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.

Results: The panel agreed on 25 recommendations and 2 good practice statements to optimize management of patients receiving anticoagulants.

Conclusions: Strong recommendations included using patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy and against using periprocedural low-molecular-weight heparin (LMWH) bridging therapy. Conditional recommendations included basing treatment dosing of LMWH on actual body weight, not using anti-factor Xa monitoring to guide LMWH dosing, using specialized anticoagulation management services, and resuming anticoagulation after episodes of life-threatening bleeding.
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http://dx.doi.org/10.1182/bloodadvances.2018024893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258922PMC
November 2018

Pharmacotherapy for Atrial Fibrillation in Patients With Chronic Kidney Disease: Insights From ORBIT-AF.

J Am Heart Assoc 2018 09;7(18):e008928

2 Duke Clinical Research Institute Durham NC.

Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019). CKD was defined as an estimated creatinine clearance <60 mL /min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant ( OAC ) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL /min. Patients with CKD were older and had higher CHA DS VAS c and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with CKD , while OAC use was lower among Stage IV and V CKD patients. After adjustment, no significant interaction was noted for OAC and CKD on all-cause mortality ( P=0.5442) or cardiovascular death ( P=0.1233), although a trend for increased major bleeding ( P=0.0608) and stroke, systemic embolism or transient ischemic attack ( P=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and CKD status on all-cause mortality ( P=0.9706), or stroke, systemic embolism or transient ischemic attack ( P=0.4218). Conclusions Patients with atrial fibrillation and CKD are less likely to be treated with rhythm control. Patients with advanced CKD are less likely to receive OAC . Finally, outcomes with OAC in patients with advanced CKD may be materially different with higher rates of both bleeding and stroke.
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http://dx.doi.org/10.1161/JAHA.118.008928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222961PMC
September 2018

Impact of Storage Lesion on Post-transfusion Rise in Hemoglobin.

Cureus 2018 Jul 9;10(7):e2952. Epub 2018 Jul 9.

Internal Medicine, Monmouth Medical Center, Long Branch, USA.

Background: The storage lesion is defined as the set of changes that occur in red blood cells (RBCs) during storage. Studies have shown that a prolonged storage period of RBCs is associated with increased destruction after transfusion. The aim of this study is to determine the impact of the storage lesion on the efficacy of RBC transfusions by comparing the mean rise in the hemoglobin of patients who received new vs old blood.

Methods: We did a retrospective chart review of all patients who received a single unit of pure red blood cell (PRBC) transfusion in a three-month period. Patients with hemolytic anemia and active bleeding were excluded. The storage lesion was estimated by calculating the number of days to expiration on the day of transfusion. Median days to expiration was calculated to be 11 days. Patients were divided into two groups based on days to expiration. Group A included patients who received old blood (days to expiration: 0-11) and group B included patients who received new blood (days to expiration: 11-38). The mean rise in hemoglobin between the two groups was compared using the paired t-test.

Results: The baseline characteristics of both groups were similar. There was no statistically significant difference in the mean rise in hemoglobin (1.01 vs 1.08- p-value 0.298), hematocrit (3.37 vs 3.61- p-value 0.249), and RBC count (0.42 vs 0.44- p-value 0.097) in the group that received old blood vs new blood, respectively.

Conclusion: An RBC transfusion with a shorter storage period does not increase hemoglobin more than RBC with a longer storage period.
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http://dx.doi.org/10.7759/cureus.2952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128591PMC
July 2018

Incremental prognostic value of renal function for stroke prediction in atrial fibrillation.

Int J Cardiol 2019 Jan 25;274:152-157. Epub 2018 Jul 25.

Duke Clinical Research Institute, Durham, NC, United States of America.

Background: Renal function has been associated with an increased stroke risk in patients with atrial fibrillation (AF). However, whether renal function incrementally adds to risk prediction in both anticoagulated and non-anticoagulated patients with AF is unclear.

Methods: We used data from the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)-a national, prospective, outpatient AF registry in patients aged >18 years (2010-2011). The association between baseline renal function and risk of stroke/systemic embolism (SSE) was evaluated in proportional hazards models adjusting for stroke risk score components. We compared discrimination of 2-year outcomes using C-indices and evaluated calibration by comparing event rates in ORBIT-AF to published rates from an external clinical trial population (ROCKET AF) and an observational cohort (ATRIA).

Results: Among 9743 patients included in the analysis, the median age was 75 years (interquartile range [IQR] 67-82), 89.5% were white, 43% were female, and 76% were taking oral anticoagulation (OAC). Over a median follow-up of 2.3 years, 214 SSE events occurred (1.00 per 100 patient-years). Continuous creatinine clearance (CrCl) was not associated with SSE risk after adjusting for other clinical factors (components of CHADS or CHADS-VASc). Discrimination for predicting stroke (C-index; 95% CI) was similar for RCHADS (0.65; 0.61-0.69), CHADS (0.65; 0.61-0.69), and CHADS-VASc (0.66; 0.62-0.70).

Conclusions And Relevance: In a community patient population with AF, renal dysfunction was not independently associated with embolic risk beyond other established risk factors in either OAC-treated or untreated patients. Additional study is needed to identify clinical factors that incrementally add to stroke risk prediction.
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http://dx.doi.org/10.1016/j.ijcard.2018.07.113DOI Listing
January 2019

Defining Minimum Necessary Anticoagulation-Related Communication at Discharge: Consensus of the Care Transitions Task Force of the New York State Anticoagulation Coalition.

Jt Comm J Qual Patient Saf 2018 11 24;44(11):630-640. Epub 2018 Jul 24.

Background: Anticoagulated patients are particularly vulnerable to ADEs when they experience changes in medical acuity, pharmacotherapy, or care setting, and resources guiding care transitions are lacking. The New York State Anticoagulation Coalition convened a task force to develop a consensus list of requisite data elements (RDEs) that should accompany all anticoagulated patients undergoing care transitions.

Methods: A multidisciplinary panel of 15 anticoagulation experts voluntarily completed an iterative Delphi process. Resources were disseminated and deliberated via remote technology, with consensus achieved via blinded electronic polling.

Results: The panel reached consensus on a list of 15 RDEs for anticoagulation communication at discharge (the ACDC List). Consensus was rapidly achieved by the full panel on 13 elements, while 3 (2 of which were combined into 1 element) required multiple iterations and achieved consensus with votes from 8 available panelists. The elements encompassed a range of factors, including drug use and indications, previous exposure and duration of therapy, recent drug exposure and laboratory results and expectations for subsequent administration, therapy goals, patient education and comprehension, and expectations for clinical management. Twelve of the elements are applicable to any anticoagulant, and 3 are specific to warfarin.

Conclusion: The ACDC List identifies specific pieces of clinical information that a panel of anticoagulant experts agree should be communicated to downstream providers for all anticoagulated patients undergoing care transitions. Additional study is needed to objectively evaluate the ability of existing care systems to communicate the elements and to assess possible relationships between communication of the elements and clinical outcomes.
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http://dx.doi.org/10.1016/j.jcjq.2018.04.015DOI Listing
November 2018

Early therapeutic persistence on dabigatran versus warfarin therapy in patients with atrial fibrillation: results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry.

J Thromb Thrombolysis 2018 Nov;46(4):435-439

Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.

Anticoagulation is highly effective for the prevention of stroke in patients with atrial fibrillation (AF) but it is dependent on patients continuing therapy. While studies have demonstrated suboptimal therapeutic persistence on warfarin, few have studied persistence rates with non vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran. We examined rates of continued use of dabigatran versus warfarin over 1 year among AF patients in the ORBIT-AF registry between June 29, 2010 and August 09, 2011. Multivariable logistic regression analysis was used to identify characteristics associated with 1-year persistent use of dabigatran therapy or warfarin. At baseline, 6.4 and 93.6% of 7150 AF patients were on dabigatran and warfarin, respectively. At 12 months, dabigatran-treated patients were less likely to have continued their therapy than warfarin-treated patients [Adjusted persistence rates: 66% (95% CI 60-72) vs. 82% (95% CI 80-84), p < .0001]. Predictors of dabigatran persistence included: CHADS-VASc risk scores ≥ 2 OR 5.69, (95% CI 1.50-21.6) and BMI greater than 25 mg/m but less than 38 kg/m 1.05 (1.01-1.09). Predictors of persistence on warfarin included: African American race (vs. White) 1.53 (1.07-2.19), Hispanic ethnicity (vs. White) 1.66 (1.06-2.60), paroxysmal and persistent AF (vs. new-onset) 1.68 (1.21-2.33) and 1.91 (1.35-2.69) respectively, LVH 1.40 (1.08-1.81), and CHADS-VASc risk scores ≥ 2 1.94 (1.18-3.19). While 1-year persistence rates for dabigatran were lower than warfarin, persistence rates for both agents were not ideal. Future studies evaluating contemporary persistence are needed in order to assist in better targeting interventions aimed to improve anticoagulation persistence.
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http://dx.doi.org/10.1007/s11239-018-1715-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182370PMC
November 2018

Therapeutic Strategies Following Major, Clinically Relevant Nonmajor, and Nuisance Bleeding in Atrial Fibrillation: Findings From ORBIT-AF.

J Am Heart Assoc 2018 06 9;7(12). Epub 2018 Jun 9.

Boston University School of Medicine, Boston, MA.

Background: Oral anticoagulation (OAC) reduces stroke risk in atrial fibrillation, but bleeding is a frequent side effect. The decision to discontinue or modify medication regimens in response to a bleeding event may differ according to bleeding site and severity.

Methods And Results: We used data from a large, national outpatient registry, ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation; 2010-2011), to evaluate event characteristics and OAC management following the first bleeding event occurring during follow-up. Bleeding events were classified into 3 categories: (1) International Society of Thrombosis and Hemostasis major bleeding, (2) clinically relevant nonmajor bleeding requiring medical attention, and (3) nuisance bleeding not requiring medical attention (eg, bruising, hemorrhoidal bleeding). Of 9743 patients enrolled in ORBIT-AF with follow-up data, 510 (3.23/100 subject-years) experienced a major bleed, 615 (3.90/100 subject-years), experienced a clinically relevant nonmajor bleed, and 1558 (9.87/100 subject-years) experienced a nuisance bleed, among first bleeds over 2 years. Nearly one third of patients (31.6%) discontinued OAC therapy following a major bleeding event, 12.7% following a clinically relevant nonmajor bleed, and 4.5% following a nuisance bleed. Compared with those who experienced a clinically relevant nonmajor or nuisance bleed, patients who experienced a major bleed were more likely to be black and female and to have a history of heart failure and stroke. Those who discontinued were more likely to have central nervous system or gastrointestinal bleeding than those who persisted on OAC therapy.

Conclusions: Overall, 1 in 3 patients who experienced a major bleed was no longer anticoagulated after the event. Those who discontinued OAC were more likely to have central nervous system or gastrointestinal bleeding than those who persisted on OAC.
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http://dx.doi.org/10.1161/JAHA.117.006391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220555PMC
June 2018

Prognostic Significance of Nuisance Bleeding in Anticoagulated Patients With Atrial Fibrillation.

Circulation 2018 08;138(9):889-897

Boston University School of Medicine, MA (E.M.H.).

Background: Bleeding is commonly cited as a reason for stopping oral anticoagulants (OACs). Whether minor bleeding events (nuisance bleeding, NB) in patients with atrial fibrillation on OACs are associated with OAC discontinuation, major bleeding, and stroke/systemic embolism (SSE) is unknown.

Methods: Within the ORBIT-AF prospective, outpatient registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we identified 6771 patients ≥18 years of age at 172 sites with atrial fibrillation and eligible follow-up visits. NB was ascertained from the medical record and was defined as minor bleeding that did not require medical attention (eg, bruising, hemorrhoidal bleeding). We used multivariable pooled logistic regression modeling to evaluate the associations between NB and major bleeding and SSE in the 180 days after documentation of NB. Our unit of analysis was the patient visit, occurring at ≈6-month intervals for a median of 1.5 years following enrollment. Changes in anticoagulation treatment satisfaction after NB were examined descriptively in a subset of patients.

Results: The median age of the overall population was 75.0 (interquartile range, 67.0-81.0); 90.0% were white and 42.5% were female. Among 6771 patients (18 560 visits), n=1357 (20.0%) had documented NB, for an incidence rate of 14.8 events per 100 person-years. Over 96.4% of patients remained on OAC therapy after the NB event. Overall, 287 (4.3%) patients experienced major bleeding and 64 (0.96%) had a SSE event during follow-up. NB was not associated with a significant increased risk of major bleeding over 6 months in models adjusting for the ATRIA bleeding score (Anticoagulation and Risk Factors in Atrial Fibrillation) (odds ratio, 1.04; 95% confidence interval, 0.68-1.60; P=0.86). NB was also not associated with increased SSE risk over 6 months in models adjusting for the CHADS-VASc risk score (odds ratio, 1.24; 95% confidence interval, 0.53-2.91; P=0.62).

Conclusions: NB is common among patients with atrial fibrillation on OACs. However, NB was not associated with a higher risk of major bleeding or SSE over the next 6 months, suggesting its occurrence should not lead to changes in anticoagulation treatment strategies in OAC-treated patients.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01165710.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.117.031354DOI Listing
August 2018

Frequency and Outcomes of Reduced Dose Non-Vitamin K Antagonist Anticoagulants: Results From ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II).

J Am Heart Assoc 2018 02 16;7(4). Epub 2018 Feb 16.

Duke Clinical Research Institute, Durham, NC.

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice.

Methods And Results: We analyzed data from the ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow-up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84, <0.0001) and had lower ORBIT bleeding risk scores (26% ≥4 versus 45%, <0.0001). Compared with those appropriately receiving standard dosing, patients receiving inappropriately reduced-dose NOACs had higher unadjusted rates of thromboembolic events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95% confidence interval 0.92-2.67) and death (6.77 versus 2.60, hazard ratio 2.61, 95% confidence interval 1.86-3.67). After adjustment, outcomes were not significantly different but tended to favor patients dosed appropriately.

Conclusions: The majority of dose reductions of NOACs in AF are inconsistent with US Food and Drug Administration recommendations. There appear to be opportunities to improve current NOAC dosing in community practice.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01701817.
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http://dx.doi.org/10.1161/JAHA.117.007633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850192PMC
February 2018

Prevalence, Characteristics, and Outcomes of Valvular Heart Disease in Patients With Atrial Fibrillation: Insights From the ORBIT-AF (Outcomes Registry for Better Informed Treatment for Atrial Fibrillation).

J Am Heart Assoc 2017 12 22;6(12). Epub 2017 Dec 22.

Duke University Medical Center, Durham, NC.

Background: The presence of valvular heart disease (VHD) may affect the risk of stroke and mortality in patients with atrial fibrillation (AF). Community-based estimates of prevalence and outcomes of specific forms of VHD in patients with AF are lacking.

Methods And Results: We examined the prevalence of VHD, anticoagulation use, mortality, stroke/transient ischemic attack, and bleeding among a community cohort of patients with AF. Significant VHD was defined as follows: (1) moderate/severe mitral stenosis or mechanical valve; (2) bioprosthetic valve, surgical repair, or balloon valvuloplasty; and (3) moderate/severe aortic regurgitation or stenosis, mitral regurgitation, or tricuspid regurgitation. Proportional hazards models were performed to test the association between VHD groups and outcomes. Among 9748 patients with AF, 2705 (27.7%) had significant VHD. Anticoagulation use was highest among patients with mitral stenosis/mechanical valve (91.8%). Compared with individuals with no significant VHD, individuals with aortic regurgitation/aortic stenosis, mitral regurgitation, or tricuspid regurgitation (hazard ratio, 1.23; 95% confidence interval, 1.07-1.42) had the highest risk of death. There were no differences in stroke or transient ischemic attack and major bleeding among individuals with and without significant VHD. Patients with AF and aortic stenosis had the highest risk of death (hazard ratio, 1.32; 95% confidence interval, 1.08-1.62).

Conclusions: Significant VHD is common among patients with AF in community practice. In a community cohort of patients with AF and CHADS-VASc score ≥2, most were anticoagulated. Individuals with AF and moderate-to-severe biological VHD have more comorbidities and a higher mortality risk; however, stroke and major bleeding are similar among those with and without significant VHD.
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http://dx.doi.org/10.1161/JAHA.117.006475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778999PMC
December 2017

International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

Am Heart J 2017 Dec 24;194:132-140. Epub 2017 Aug 24.

Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment.

Methods: Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks).

Results: Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHADS-VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHADS-VASc=0 and 69% and 87% for CHADS-VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II).

Conclusions: Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement.
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http://dx.doi.org/10.1016/j.ahj.2017.08.011DOI Listing
December 2017

Treatment of Atrial Fibrillation and Concordance With the American Heart Association/American College of Cardiology/Heart Rhythm Society Guidelines: Findings From ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation).

Circ Arrhythm Electrophysiol 2017 Nov;10(11)

From the Duke Center for Atrial Fibrillation, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (A.S.B., S.K., L.E.T., E.D.P., J.P.P.); Ahmanson-UCLA Cardiomyopathy Center, Ronald Reagan-UCLA Medical Center (G.C.F.); Columbia University College of Physicians and Surgeons, New York, NY (J.A.R.); University of Colorado School of Medicine, Aurora (L.A.A.); Yale University School of Medicine, New Haven, CT (J.V.F.); Penn State Hershey Heart and Vascular Institute (G.N.); Stanford University School of Medicine, CA (K.W.M.); Kaiser Permanente Division of Research, Oakland, CA (A.S.G.); Lankenau Institute for Medical Research and Jefferson Medical College, Philadelphia, PA (P.R.K.); Hofstra Northwell School of Medicine, New York, NY (J.E.A.); Mayo Clinic and Mayo Clinic College of Medicine, Rochester, MN (B.J.G.); and Boston University Medical Center, MA (E.M.H.).

Background: It is unclear how frequently patients with atrial fibrillation receive guideline-concordant (GC) care and whether guideline concordance is associated with improved outcomes.

Methods And Results: Using data from ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we determined how frequently patients received care that was concordant with 11 recommendations from the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society atrial fibrillation guidelines pertaining to antithrombotic therapy, rate control, and antiarrhythmic medications. We also analyzed the association between GC care and clinical outcomes at both the patient level and center level. A total of 9570 patients were included. The median age was 75 years (interquartile range, 67-82), and the median CHADS-VASc score was 4 (interquartile range, 3-5). A total of 5977 patients (62.5%) received care that was concordant with all guideline recommendations for which they were eligible. Rates of GC care were higher in patients treated by providers with greater specialization in arrhythmias (60.0%, 62.4%, and 67.0% for primary care physicians, cardiologists, and electrophysiologists, respectively; <0.001). During a median of 30 months of follow-up, patients treated with GC care had a higher risk of bleeding hospitalization (hazard ratio=1.21; =0.021) but a similar risk of death, stroke, major bleeding, and all-cause hospitalization.

Conclusions: Over a third of patients with atrial fibrillation in this large outpatient registry received care that differed in some respect from guideline recommendations. There was no apparent association between GC care and improved risk-adjusted outcomes.
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http://dx.doi.org/10.1161/CIRCEP.117.005051DOI Listing
November 2017

Management and outcomes of patients with atrial fibrillation and a history of cancer: the ORBIT-AF registry.

Eur Heart J Qual Care Clin Outcomes 2017 07;3(3):192-197

MLH Heart Center, Lankenau MOB, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.

Aims: The presence of cancer can complicate treatment choices for patients with atrial fibrillation (AF) increasing both the risk of thrombotic and bleeding events.

Methods And Results: Using data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we aimed to characterize AF patients with cancer, to describe their management and to assess the association between cancer and cardiovascular (CV) outcomes. Among 9749 patients, 23.8% had history of cancer (57% solid malignancy, 1.3% leukaemia, 3.3% lymphoma, 40% other type, and 2.2% metastatic cancer). Patients with history of cancer were older, more likely to have CV disease, CV risk factors, and prior gastrointestinal bleeding. No difference in antiarrhythmic and antithrombotic therapy was observed between those with and without cancer. Patients with history of cancer had a significantly higher risk of death (7.8 vs. 4.9 deaths per 100 patient-years follow-up, P = 0.0003) mainly driven by non-CV death (4.2 vs. 2.4 per 100 patient-years follow-up; P = 0.0004) and higher risk of major bleeding (5.1 vs. 3.5 per 100 patient-years follow-up; P = 0.02) compared with non-cancer patients; no differences were observed in risks of strokes/non-central nervous system embolism (1.96 vs. 1.48, P = 0.74) and CV death (2.89 vs. 2.07, P = 0.35) between the two groups.

Conclusion: A history of cancer is common among AF patients with up to one in four patients having both. Antithrombotic therapy, rates of cerebrovascular accident, other thrombotic events and cardiac death were similar in AF patients with or without a history of cancer. Patients with cancer, however, were at higher risk of major bleeding and non-CV death.
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http://dx.doi.org/10.1093/ehjqcco/qcx004DOI Listing
July 2017

Disease understanding in patients newly diagnosed with atrial fibrillation.

Heart 2018 03 8;104(6):494-501. Epub 2017 Aug 8.

Duke Clinical Research Institute, Durham, North Carolina, USA.

Objective: To describe self-reported disease understanding for newly diagnosed patients with atrial fibrillation (AF) and assess (1) how disease understanding changes over the first 6 months after diagnosis and (2) the relationship between patient understanding of therapies at baseline and treatment receipt at 6 months among treatment-naïve patients.

Methods: We analysed survey data from SATELLITE (Survey of Patient Knowledge and Personal Priorities for Treatment), a substudy of patients with new-onset AF enrolled in the national Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT) II registry across 56 US sites. Patients were surveyed at the baseline and 6-month follow-up clinic visits using Likert scales.

Results: Among 1004 baseline survey responses, patients' confidence in their understanding of rhythm control, ablation, anticoagulation and cardioversion was suboptimal, with 'high' understanding ranging from 8.5% for left atrial appendage closure to 71.3% for rhythm therapy. Of medical history and demographic factors, education level was the strongest predictor of reporting 'high' disease understanding. Among the 786 patients with 6-month survey data, significant increases in the proportion reporting high understanding were observed (p<0.05) only for warfarin and direct oral anticoagulants (DOACs). With the exception of ablation, high understanding for a given therapeutic option was not associated with increased use of that therapy at 6 months.

Conclusions: About half of patients with new-onset AF understood the benefits of oral anticoagulant at the time of diagnosis and understanding improved over the first 6 months. However, understanding of AF treatment remains suboptimal at 6 months. Our results suggest a need for ongoing patient education.

Clinical Trial Registration: Clinicaltrials.gov. Identifier: NCT01701817.
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http://dx.doi.org/10.1136/heartjnl-2017-311800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861387PMC
March 2018

Stroke Prevention in Atrial Fibrillation in the Very Elderly: Anticoagulant Therapy Is No Longer a Sin.

Authors:
Jack Ansell

J Am Heart Assoc 2017 07 23;6(7). Epub 2017 Jul 23.

Hofstra Northwell School of Medicine, Hempstead, NY, USA

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http://dx.doi.org/10.1161/JAHA.117.006864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586331PMC
July 2017

Factors associated with non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with new-onset atrial fibrillation: Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II (ORBIT-AF II).

Am Heart J 2017 Jul 4;189:40-47. Epub 2017 Apr 4.

Duke University Medical Center, Durham, NC; Duke Clinical Research Institute, Durham, NC.

Background: Several non-vitamin K antagonist oral anticoagulant (NOAC) alternatives to warfarin are available for stroke prevention in atrial fibrillation (AF). We aimed to describe the factors associated with selection of NOACs versus warfarin in patients with new onset AF.

Methods: The ORBIT-AF II study is a national, US, prospective, observational, cohort study of anticoagulation treatment in patients with AF receiving NOACs or warfarin in the United States from 2013 to 2016. We measured factors associated with oral anticoagulant selection in 4,670 patients recently diagnosed with AF.

Results: At baseline, 1,169 (25%) patients were started on warfarin and 3,501 (75%) on NOACs: of these latter, 259 (6%) were started on dabigatran, 1858 (40%) on rivaroxaban, and 1384 (30%) on apixaban. Those receiving NOACs were slightly younger patients (median age 71 vs 72, P<.0001); were less likely to have prior stroke (5.3% vs 8.6%; P<.0001) or prior bleeding (2.7% vs 4.4%; P=.005); had better kidney function (mean estimated glomerular filtration rate 91 mL/min vs 80 mL/min, P<.0001); and had fewer patients at high stroke risk (CHADS-VASc score [Congestive heart failure, Hypertension, Age ≥75years, Diabetes mellitus, Prior stroke, transient ischemic attack {TIA}, or thromboembolism,Vascular disease, Age 65-74years, Sex category {female}] ≥2 in 86% vs 93%; P<.0001). In multivariable analysis, factors associated with NOAC selection versus warfarin included renal function, prior stroke or valve replacement, rhythm control AF management strategy, treatment by a cardiologist, and higher patient education level.

Conclusions: In contemporary clinical practice, up to three-fourths of patients with new-onset AF are now initially treated with a NOAC for stroke prevention. Those selected for NOAC treatment had lower stroke and bleeding risk profiles, were more likely treated by cardiologists, and had higher socioeconomic status.

Trial Registration: clinicaltrials.gov Identifier: NCT01701817.
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http://dx.doi.org/10.1016/j.ahj.2017.03.024DOI Listing
July 2017

Oral anticoagulation management in patients with atrial fibrillation undergoing cardiac implantable electronic device implantation.

Clin Cardiol 2017 Sep 19;40(9):746-751. Epub 2017 May 19.

Cardiac Electrophysiology Section, Duke Center for Atrial Fibrillation, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.

Background: Oral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non-vitamin K antagonist oral anticoagulants (NOACs) have not been characterized.

Hypothesis: Anticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation.

Methods: Using the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status.

Results: Among 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow-up of 30 months (interquartile range, 24-36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65-77.5 years] vs 77 years [range, 70-82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7-99.0] vs 65.8 [range, 50.0-91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty-day periprocedure bleeding and stroke adverse events were infrequent.

Conclusions: Management of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin- and NOAC-treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC-treated patients.
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http://dx.doi.org/10.1002/clc.22726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638096PMC
September 2017

Management of Major Bleeding in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice (from Phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF II]).

Am J Cardiol 2017 05 28;119(10):1590-1595. Epub 2017 Mar 28.

Department of Medicine, Duke University Medical Center, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina.

Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement.
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http://dx.doi.org/10.1016/j.amjcard.2017.02.015DOI Listing
May 2017

Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial.

JAMA Cardiol 2017 05;2(5):525-534

Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.

Importance: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial.

Objective: To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system.

Design, Setting, And Participants: This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011.

Interventions: Apixaban therapy vs warfarin therapy.

Main Outcomes And Measures: Within-trial resource use and cost were compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed.

Results: Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$60; 95% CI, -$2728 to $2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($53 925 per quality-adjusted life year, with 98% likelihood of meeting a $100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon.

Conclusions And Relevance: Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness.

Trial Registration: clinicaltrials.gov Identifier: NCT00412984.
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http://dx.doi.org/10.1001/jamacardio.2017.0065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814979PMC
May 2017

Thrombophilic Evaluation in Patients with Acute Pulmonary Embolism.

Semin Respir Crit Care Med 2017 02 16;38(1):107-120. Epub 2017 Feb 16.

Department of Medicine, Hofstra Northwell, School of Medicine, Hempstead, New York.

Patients with acute pulmonary embolism (PE) are often tested for thrombophilias, which are hereditary and acquired conditions that predispose to thrombosis. If a hereditary condition is identified, then testing is often performed on members of the patient's family. Testing for these conditions can be complex, as the presence of acute thrombosis and antithrombotic therapies can make the results of many tests unreliable. Many risk factors for thrombosis exist that are not routinely assessed by laboratory testing, and it is likely that many hereditary thrombophilia conditions remain to be discovered. Also, various risk factors for thrombosis interact with one another. Therefore, the results of a laboratory thrombophilia evaluation provide a limited ability to assess a patient or family members' risk for future thrombosis, and such testing usually does not provide information that improves a management decision. Thrombophilia testing is expensive and carries potential risks. This article reviews common thrombophilias, their epidemiology and classification, and timing and technical aspects of accurate testing and provides rational suggestions for the use of thrombophilia testing in five clinical situations: (1) following provoked PE (or other venous thromboembolism), (2) following unprovoked venous thromboembolism, (3) in relatives of patients with thrombosis, (4) in female relatives of patients with thrombosis considering estrogen use, and (5) in female relatives of patients with thrombosis who are considering pregnancy. Published guidelines and guidance statements from professional societies and other groups are also reviewed. Clinicians should carefully consider the relevant risks and benefits before testing patients for thrombophilia. When performed, testing should be timed correctly and care should be taken to properly interpret results. New models that incorporate multiple genetic and clinical markers may improve the utility of testing, but these await further research.
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http://dx.doi.org/10.1055/s-0036-1597564DOI Listing
February 2017