Greg Flaker

University of Missouri, Columbia, Missouri, United States

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Publications (152)1292.06 Total impact

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    ABSTRACT: Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 08/2015; DOI:10.1097/MBC.0000000000000397 · 1.38 Impact Factor
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    ABSTRACT: Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 04/2015; 65(13):1340-1360. DOI:10.1016/j.jacc.2015.01.049 · 15.34 Impact Factor
  • Rachel Littrell · Greg Flaker
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    ABSTRACT: Atrial fibrillation (AF) is an increasingly common cardiac arrhythmia, currently affecting more than 5 million Americans. Management of patients with AF can be complex, with key strategies including selecting rhythm control versus heart rate control and reducing the patient's risk of stroke or other systemic embolization. The American Heart Association, American College of Cardiology, and Heart Rhythm Society released 2014 Guideline for the Management of Patients with Atrial Fibrillation, which outlines several new recommendations with important clinical implications. Among these are a new recommendation to use the CHA2DS2-Vasc score for stroke risk assessment, rather than the previously advised CHADS2 score, expansion of anticoagulation options in selected patients, decreased emphasis on the role of aspirin, and an increased emphasis on the role of catheter ablation.
    Postgraduate Medicine 03/2015; DOI:10.1080/00325481.2015.1029863 · 1.54 Impact Factor
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    ABSTRACT: Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted pre-procedure; whether bridging therapy was used; and the proportion of patients who experienced important clinical outcomes during the 30 days post-procedure. Of 10,674 procedures performed during follow-up in 5924 patients, 9260 were included in this analysis. Anticoagulant treatment was not interrupted pre-procedure 37.5% of the time. During the 30 days post-procedure, stroke or systemic embolism occurred after 16/4624 (0.35%) procedures among apixaban-treated patients and 26/4530 (0.57%) procedures among warfarin-treated patients (OR 0.601; 95% CI 0.322-1.120). Major bleeding occurred in 74/4560 (1.62%) procedures in the apixaban arm and 86/4454 (1.93%) in the warfarin arm (OR 0.846; 95% CI 0.614-1.166). The risk of death was similar with apixaban (54/4624 [1.17%]) and warfarin (49/4530 [1.08%]) (OR 1.082; 95% CI 0.733-1.598). Among patients in ARISTOTLE, the 30-day post-procedure stroke, death, and major bleeding rates were low and similar in apixaban- and warfarin-treated patients, regardless of whether anticoagulation was stopped beforehand. Our findings suggest that many patients on chronic anticoagulation can safely undergo procedures; some will not require a pre-procedure interruption of anticoagulation. ARISTOTLE ClinicalTrials.gov number (NCT00412984).
    Blood 10/2014; 124(25). DOI:10.1182/blood-2014-08-595496 · 10.43 Impact Factor
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    ABSTRACT: Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin.
    Journal of the American College of Cardiology 10/2014; 64(15):1541-50. DOI:10.1016/j.jacc.2014.07.967 · 15.34 Impact Factor
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    ABSTRACT: Approximately half of patients with atrial fibrillation (AF) and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs), and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to develop and disseminate shared decision-making tools, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational datasets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives.
    American Heart Journal 09/2014; 168(3). DOI:10.1016/j.ahj.2014.04.007 · 4.56 Impact Factor
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    ABSTRACT: Electronic control devices (ECDs) are weapons used to incapacitate violent subjects. Subjects have died suddenly after ECD application, but because cardiac dysrhythmias have been inconsistently observed during ECD application in animals, the cause for death is uncertain.
    Journal of Emergency Medicine 08/2014; 47(4). DOI:10.1016/j.jemermed.2014.06.019 · 1.18 Impact Factor
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    Jad Omran · Ben Nordhues Md · Blake Buchert · Greg C Flaker
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    ABSTRACT: Background In patients with warfarin-induced major bleeding, prompt administration of reversal agents increases coagulation factors and may allow early surgical correction of bleeding. However even with reversal agents, mortality is high. In this analysis the type and timing of reversal agents were evaluated Methods Review of warfarin treated non-trauma patients admitted to a University Hospital with ISTH defined major bleeding between October 2009 and January 2013. Results 84 patients met entry criteria with a mean age 67.8 ± 14.3 years including 46 % females. The mean INR on admission was 3.6 ± 2.4. The site of major bleeding was central nervous system in 33 (39%), abdomen in 28 (33%), chest in 6 (7%) and other in 15 (18 %). Reversal agents including vitamin K, fresh frozen plasma (FFP), or prothrombin complex concentrate (PCC) were given to 83 patients. Forty patients required either major surgery (25 patients) or a therapeutic procedure (14 patients) to stop bleeding. Death occurred in 15 patients (18%) but the admission INR was not predictive of mortality (p=0.52, Kruskal-Wallis test). The INR was never completely corrected (INR<1.1) in 31 (37%) patients, 9 of whom died. Conclusions Patients with warfarin-induced major bleeding receive ineffective anticoagulation reversal, have delayed times to therapeutic procedures, and have a high mortality rate. Whether earlier administration of these agents or administration of newer agents would reduce hospital mortality requires further study.
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    Atul Singla · Mayank Mittal · Greg C Flaker
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    ABSTRACT: Abstract: Stroke prevention is a crucial step in the management of atrial fibrillation (AF). The assessment of stroke risk associated with AF varies, depending on the presence of various clinical risk factors (older age, congestive heart failure, diabetes mellitus, hypertension, history of stroke or transient ischemic attack, female sex, or peripheral vascular disease) incorporated in risk stratification models such as CHADS2 and CHA2DS2-VASc. Although these models have modest predictive ability in individual patients, current guidelines advocate the use of a CHA2DS2-VASc risk score to identify very low risk patients who can avoid antithrombotic therapy, as well as all others who can benefit from such therapy. More recently biomarkers and imaging has improved our knowledge of pathophysiology of AF and may further improve risk stratification for thromboprophylaxis in AF patients. These new markers combined with clinical risk scores may enable the development of novel tools to improve clinical risk assessment in AF. In this article, we summarize the recent developments in risk stratification for stroke prevention in AF, including the various schemes and new biomarkers that may lead to improved patient outcomes. Keywords: atrial fibrillation, anticoagulant therapy, CHADS2, risk stratification, CHA2DS2-VASc, biomarkers
    04/2014; 2014(5):83-92. DOI:10.2147/RRCC.S39091
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    ABSTRACT: Objectives The aim of this study was to determine the risk of major clinical and thromboembolic events after cardioversion for atrial fibrillation in subjects treated with apixaban, an oral factor Xa inhibitor, compared with warfarin. Background In patients with atrial fibrillation, thromboembolic events may occur after cardioversion. This risk is lowered with vitamin K antagonists and dabigatran. Methods Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, we conducted a post-hoc analysis of patients undergoing cardioversion. Results A total of 743 cardioversions were performed in 540 patients: 265 first cardioversions in patients assigned to apixaban and 275 in those assigned to warfarin. The mean time to the first cardioversion for patients assigned to warfarin and apixaban was 243 ± 231 days and 251 ± 248 days, respectively; 75% of the cardioversions occurred by 1 year. Baseline characteristics were similar between groups. In patients undergoing cardioversion, no stroke or systemic emboli occurred in the 30-day follow-up period. Myocardial infarction occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Major bleeding occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Death occurred in 2 patients (0.5%) receiving warfarin and 2 patients receiving apixaban (0.6%). Conclusions Major cardiovascular events after cardioversion of atrial fibrillation are rare and comparable between warfarin and apixaban. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984)
    Journal of the American College of Cardiology 01/2014; 63(11):1082–1087. · 15.34 Impact Factor
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    ABSTRACT: To determine the risk of major clinical and thromboembolic events after cardioversion for atrial fibrillation in subjects treated with apixaban, an oral factor Xa inhibitor compared with warfarin. In patients with atrial fibrillation (AF), thromboembolic events may occur after cardioversion. This risk is lowered with vitamin K antagonists and dabigatran. Using data from ARISTOTLE, we conducted a post-hoc analysis of patients undergoing cardioversion. A total of 743 cardioversions in 540 patients were performed: 265 first cardioversions in patients assigned to apixaban and 275 in those receiving warfarin. The mean time to the first cardioversion for patients assigned to warfarin and apixaban was 243 + 231 and 251 + 248 days respectively; 75% of the cardioversions occurred by 1 year. Baseline characteristics were similar between groups. In patients undergoing cardioversion, no stroke or systemic emboli occurred in the 30 day follow-up period. MI occurred in 1 patient (0.2%) receiving warfarin and 1 receiving apixaban (0.3%). Major bleeding occurred in 1 patient (0.2%) receiving warfarin and 1 receiving apixaban (0.3%). Death occurred in 2 patients (0.5%) receiving warfarin and 2 patients receiving apixaban (0.6%). Major cardiovascular events after cardioversion of AF are rare and comparable between warfarin and apixaban.
    Journal of the American College of Cardiology 10/2013; 63(11). DOI:10.1016/j.jacc.2013.09.062 · 15.34 Impact Factor
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    ABSTRACT: Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients. Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS2). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001). The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.
    American heart journal 09/2013; 166(3):549-58. DOI:10.1016/j.ahj.2013.05.016 · 4.56 Impact Factor
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    ABSTRACT: Background: Following cardiac resynchronization therapy (CRT), the paced QRS duration may be more prolonged than the preoperative QRS. The outcome for these patients with a +QRS duration is uncertain. Methods: Analysis of 100 consecutive patients with successful CRT implantation. Results: 37 patients had a +QRS duration. Compared with those with a –QRS duration, these had a shorter baseline QRS (150.1 versus 176 ms, p50.001) and more often had either anterior/lateral (QRS¡28.5 ms) or posterior vein (QRS¡3 ms) left ventricular (LV) lead location. Of 22 patients who improved by two classes, the mean difference in QRS was 218.1 ms. Of the 35 who improved by one class, the mean QRS difference was 215 ms. Of the 35 whose functional class did not improve, the mean QRS difference was +5.0 ms. Of the eight who worsened, the mean difference was +33 ms. Transthoracic echocardiograms at 3–6 months showed that a –QRS duration was associated with a higher mean LV ejection fraction and smaller left ventricular end diastolic dimension. Conclusions: A +QRS duration is associated with a worse clinical outcome. These patients have poorer LV function and size. Measurement of the paced QRS at the time of implantation, focusing on obtaining a –QRS duration, may improve outcomes in patients undergoing CRT.
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    ABSTRACT: BACKGROUND: During follow up of between 1 and 3 years in the RE-LY trial, two doses of dabigatran etexilate were shown to be effective and safe for prevention of stroke or systemic embolism in patients with atrial fibrillation (AF). There is a need for longer term follow up of patients on dabigatran and for further data comparing the two dabigatran doses. METHODS AND RESULTS: Patients randomized to dabigatran in RE-LY were eligible for RELY-ABLE if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow up 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomized to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46 and 1.60 %/year on dabigatran 150 and 110 mg bid, respectively (hazard ratio (HR) 0.91, 95% confidence interval (CI), 0.69-1.20). Rates of major hemorrhage were 3.74 and 2.99 %/year on dabigatran 150 and 110 mg (HR 1.26, 95% CI, 1.04-1.53). Rates of death were 3.02 and 3.10 %/year (HR 0.97; 95% CI 0.80-1.19). Rates of hemorrhagic stroke were; 0.13 and 0.14%/year. CONCLUSIONS: During 2.3 years continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily compared to 110 mg, and similar rates of stroke and death. CLINICAL TRIAL REGISTRATION INFORMATION: Clinicaltrials.gov; Identifier: NCT00808067.
    Circulation 06/2013; 128(3). DOI:10.1161/CIRCULATIONAHA.112.001139 · 14.95 Impact Factor
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    Journal of the American College of Cardiology 03/2013; 61(10). DOI:10.1016/S0735-1097(13)60338-1 · 15.34 Impact Factor
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    Journal of the American College of Cardiology 03/2013; 61(10). DOI:10.1016/S0735-1097(13)60317-4 · 15.34 Impact Factor
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    ABSTRACT: BACKGROUND: -The impact of apixaban versus aspirin on ischaemic stroke and major bleeding in relation to the CHADS(2) and CHA(2)DS(2)-VASc stroke risk scores in atrial fibrillation(AF) has not been investigated. METHODS AND RESULTS: -In this secondary analysis of the AVERROES trial, our principal objective was to assess the effect of treatment with aspirin or apixaban on ischemic stroke and major bleeding, in relation to the CHADS(2)/CHA(2)DS(2)-VASc scores. We found no significant heterogeneity for treatment efficacy on ischaemic stroke for apixaban when subdivided by stroke risk strata, based on CHADS(2)/CHA(2)DS(2)-VASc. Effects were consistent irrespective of baseline risk and thus, absolute benefits were greatest in the high risk groups. There was also no significant heterogeneity for apixaban vs aspirin with regard to major bleeding, when subdivided by CHADS(2)/CHA(2)DS(2)-VASc scores. In multivariable analysis, significant predictors of stroke on aspirin were age &[ge]75 years, prior stroke or TIA, estimated GFR<60 mL/min and non-paroxysmal AF. Proportions of the study cohort classified as low/moderate/high risk using the CHADS(2) and CHA(2)DS(2)-VASc scores were 0.3%/71.7%/28.1% and <0.1%/10.5%/89.5%, respectively. CONCLUSIONS: -In an AF population, apixaban was superior to aspirin for stroke prevention, with similar rates of major bleeding, in the presence of one or more stroke risk factors, with consistency of the treatment effect by CHADS(2)/CHA(2)DS(2)-VASc scores.
    Circulation Arrhythmia and Electrophysiology 02/2013; 6(1). DOI:10.1161/CIRCEP.112.975847 · 5.42 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Apixaban reduces stroke with comparable bleeding risks when compared with aspirin in patients with atrial fibrillation who are unsuitable for vitamin k antagonist therapy. This analysis explores patterns of bleeding and defines bleeding risks based on stroke risk with apixaban and aspirin. METHODS: The Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin k Antagonist Treatment (AVERROES) trial randomized 5599 patients with atrial fibrillation and risk factors to receive either apixaban or aspirin. Bleeding events were defined as the first occurrence of either major bleeding or clinically relevant nonmajor bleeding. RESULTS: The rate of a bleeding event was 3.8%/year with aspirin and 4.5%/year with apixaban (hazard ratio with apixaban, 1.18; 95% CI, 0.92-1.51; P=0.19). The anatomic site of bleeding did not differ between therapies. Risk factors for bleeding common to apixaban and aspirin were use of nonstudy aspirin >50% of the time and a history of daily/occasional nosebleeds. The rates of both stroke and bleeding increased with higher CHADS(2) scores but apixaban compared with aspirin was associated with a similar relative risk of bleeding (P interaction 0.21) and a reduced relative risk of stroke (P interaction 0.37) irrespective of CHADS(2) category. CONCLUSIONS: Anatomic sites and predictors of bleeding are similar for apixaban and aspirin in these patients. Higher CHADS(2) scores are associated with increasing rates of bleeding and stroke, but the balance between risks and benefits of apixaban compared with aspirin is favorable irrespective of baseline stroke risk.Clinical Trial Registration Information-www.clinicaltrials.gov. Unique identifier: NCT 00496769.
    Stroke 10/2012; 43(12). DOI:10.1161/STROKEAHA.112.664144 · 6.02 Impact Factor
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    Manish B Jhawar · Greg Flaker
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    ABSTRACT: Atrial fibrillation is the most common of the cardiac arrhythmias and is associated with high risk of stroke and systemic thromboembolism. Prevention of these complications is therefore a major component of clinical management in patients with this rhythm disorder. The choice of antithrombotic therapy in any given patient depends on his or her risk profile and needs to be carefully balanced against the risk of bleeding. In this review we discuss the pathophysiology of thrombogenesis in atrial fibrillation, risk factors for systemic thromboembolism in atrial fibrillation, patient risk stratification modules both for systemic thromboembolism and the risk of bleeding, current antithrombotic therapy strategies, clinicoepidemiological evidence that led to their evolvement, the challenges that plague them, recent developments in the field and how they could possibly affect our future clinical decision making.
    Hematology Research and Reviews 04/2012; 3:1-13. DOI:10.2147/JBM.S19827
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    Journal of the American College of Cardiology 03/2012; 59(13). DOI:10.1016/S0735-1097(12)60573-7 · 15.34 Impact Factor

Publication Stats

11k Citations
1,292.06 Total Impact Points

Institutions

  • 1983–2014
    • University of Missouri
      • • Department of Internal Medicine
      • • Department of Health Sciences
      • • Department of Surgery
      • • Department of Psychiatry
      Columbia, Missouri, United States
  • 2013
    • University of Washington Seattle
      • Division of Hematology
      Seattle, Washington, United States
  • 2010–2011
    • McMaster University
      • Population Health Research Institute (PHRI)
      Hamilton, Ontario, Canada
  • 2007
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 2004
    • American College of Cardiology
      Washington, Washington, D.C., United States
  • 1992–2004
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, Massachusetts, United States
    • Palm Drive Hospital
      Sebastopol, California, United States
  • 1997
    • Mount Sinai Medical Center
      New York City, New York, United States
    • University of Pennsylvania
      • Department of Medicine
      Philadelphia, PA, United States
  • 1992–1995
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States