Anticoagulation – Full Curriculum

Anticoagulation – Full Curriculum

The Epidemic of Atrial Fibrillation Projected US Prevalence
Anticoagulation HRS Education 4/14/2017 9:23 PM 18 16 14 12 Projected Number of People With AF (millions) 10 Take home point: AF will attain epidemic status over the next 50 years. 8 Based on Projected Incidence 6 Based on Current Incidence 4 2 Year 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 Miyakasa et al. Circulation. 2006;114: 2

Classification of AF ACC/AHA/ESC Guidelines
Anticoagulation HRS Education 4/14/2017 9:23 PM First Detected Take home point: AF can be divided into categories based on persistency of rhythm disturbance. Paroxysmal (Self-terminating) Persistent (Not self-terminating) Permanent Fuster et al. J Am Coll Cardiol. 2006;48: 3

Pharmacologic Management of Patients With Newly Discovered AF ACC/AHA/ESC Guidelines
Anticoagulation HRS Education 4/14/2017 9:23 PM Newly Discovered AF Paroxysmal Persistent No therapy needed, unless severe symptoms (eg, hypotension, HF, angina pectoris) Accept permanent AF Rate control and anticoagulation, as needed Take home point: Regardless of management strategy, anticoagulation is a key component to management. Anticoagulation and rate control, as needed Consider antiarrhythmic drug therapy Anticoagulation, as needed Cardioversion Long-term drug prevention unnecessary Fuster et al. J Am Coll Cardiol. 2006;48: 4

Pharmacologic Management of Patients With Recurrent Paroxysmal AF Sinus Rhythm Maintenance
Anticoagulation HRS Education 4/14/2017 9:23 PM Recurrent Paroxysmal AF Minimal or no symptoms Disabling symptoms in AF Anticoagulation and rate control, as needed Anticoagulation and rate control, as needed Take home point: Whether or not antiarrhythmic agents are used in paroxysmal AF, the need for anticoagulation should always be considered. AAD therapy No drug for prevention of AF AF ablation if AAD treatment fails Fuster et al. J Am Coll Cardiol. 2006;48: 5

Costs of Stroke in the United States
Anticoagulation HRS Education 4/14/2017 9:23 PM $3.4 billion paid on behalf of Medicare beneficiaries discharged from short-stay hospitals for stroke in the United States $5692 per discharge Initial hospital stay accounts for over 70% of costs worldwide Take home point: Stroke is debilitating and expensive. Background: The cost of treating patients with a stroke in the United States is high. In 1999 alone, $3.4 billion were paid to Medicare beneficiaries discharged from short-stay hospitals for stroke. This averaged to $5692 per each discharged patient. The cost of stroke is not confined to the United States, however; it is a worldwide issue. In the United Kingdom, cost per stroke patient over a 12-week period ranged from $298 to $110,032 (a mean of $13,668), based on an analysis by Caro et al of 2 12-week international trials designed to assess safety and efficacy of a new neuroprotective agent. The analysis calculated the mean cost of study populations in France ($11,703), Germany ($9840), and Sweden ($14,492) as well. The biggest contributor to the high costs associated with stroke was the initial hospitalization, accounting for over 70% of these costs worldwide. American Heart Association. Heart Disease and Stroke Statistics–2004 Update. Caro et al. Stroke. 2000;31: 6

Studies of Stroke in Patients With AF
Anticoagulation HRS Education 4/14/2017 9:23 PM Stroke Mortality 6 4 2 8 Relative Risk Take home point: The incidence of stroke and death in patients with AF who are not anticoagulated is substantial. Whitehall Whitehall Regional Heart Study Framingham (no heart disease) Framingham Framingham (overall) Manitoba Fuster et al. J Am Coll Cardiol. 2006;48: 7

Stroke Rates in Placebo-Treated Patients With AFa
Anticoagulation HRS Education 4/14/2017 9:23 PM Stroke (%) Take home point: In earlier clinical trials, stroke risk was between 5 and 9% in patients with no prior stroke and nearly 25% in patients with prior stroke. AFASAK SPAF BAATAF CAFA SPINAF EAFTb aPatients not anticoagulated; bSecondary prevention. Hart et al. Ann Intern Med. Ann Intern Med. 2007;146: 8

Stroke Rates by Age in Patients With AF in Untreated Control Groups
Anticoagulation HRS Education 4/14/2017 9:23 PM 9 8 7 6 5 Stroke Rate (%/year) 4 Take home point: Stroke risk in AF is very high. 3 2 1 <65 65-75 >75 Age (years) Fuster et al. J Am Coll Cardiol. 2006;48: 9

Severity of Stroke With AF
Anticoagulation HRS Education 4/14/2017 9:23 PM 1061 patients admitted with acute ischemic stroke 20.2% had AF Bedridden state With AF 41.2% Without AF 23.7% Odds ratio for bedridden state following stroke due to AF: 2.23 (95% CI, ; P<.0005) Take home point: The severity of stroke in patients with AF is higher than non-AF strokes. Background: In order to assess if the severity of AF-associated acute ischemic stroke is worse than ischemic stroke associated with other etiologies, Dulli et al examined an acute ischemic stroke patient population for the clinical characteristics of acute ischemic stroke in patients with and without underlying AF in a retrospective study. AF was present in 20.2% of the patient population (acute ischemic stroke patients admitted between 1990 and 2001). Many of the factors associated with ischemic stroke varied between patients with AF and without AF. Hypertension, ischemic heart disease, and other cardioembolic risks were significantly higher in patients with AF. The study also showed that the frequency of the bedridden state was markedly higher in patients with AF (41.2%) versus patients without AF (23.7%); P< The odds ratio for the bedridden state following stroke with AF was 2.23 (95% CI, ; P<.0005). The significance of AF in the severity of stroke compared with other variables demonstrated that AF was a strong independent predictor of severe ischemic stroke. The study also showed that the disability caused by acute ischemic stroke increases with age, and is significantly worse when associated with AF in groups aged 65 to 74 (P<.05) and 75 to 84 years (P<.0005). The study investigators concluded that acute ischemic stroke in the presence of underlying AF is often more severe than ischemic stroke due to other etiologies. Dulli et al. Neuroepidemiology. 2003;22: 10

Thrombogenicity in AF: Additional Factors
Anticoagulation HRS Education 4/14/2017 9:23 PM Prothrombotic compounds are increased in the fibrillating atrium Coagulation Factor VII Fibrinogen D-dimer Prothrombin fragment Thrombin-antithrombin complex Altered fibrinolytic balance Increased superoxides in LAA (which degrade NO) Platelets P-selectin -thromboglobulin Platelet factor 4 NO secretion by arterial endothelium and atrium reduced Due to loss of laminar flow and decreasing stretch periods Time course of recovery following SR restoration unknown Atrial abnormalities may exist independently of AF Take home point: There are numerous other factors leading to an increased risk for stroke in AF. Gustafsson et al. Stroke. 1990;21:47-51; Feng et al. Am J Cardiol. 2001;87: ; Leong et al. Am J Cardiol. 2000;86: ; Heppell et al. Heart. 1997;77: ; Mitusch et al. Thromb Haemost. 1996;75: ; Nagao et al. Stroke. 1995;26: 11

Anticoagulation in AF: Stroke Risk Reductions
Anticoagulation HRS Education 4/14/2017 9:23 PM Warfarin Better Control Better AFASAK Reduction of all-cause mortality RRR 26% SPAF BAATAF Take home point: The use of warfarin has demonstrated significant risk reduction for stroke in AF. Background: This slide illustrates risk reductions for warfarin versus control in stroke across several AF trials. Overall relative risk reduction was 62%, which was statistically significant in 4 of the trials, SPAF, BAATAF, SPINAF, and EAFT. Of the primary-prevention trials, the combined reduction was 59%. EAFT, the only secondary-prevention trial, had a 68% risk reduction. The relative risk reduction of all-cause mortality was 26%. CAFA SPINAFa Reduction of stroke RRR 62% EAFT Aggregate 100% 50% -50% -100% aOnly SPINAF used placebo-controlled, double-blind design; no women included. Hart et al. Ann Intern Med. 1999;131: 12

Anticoagulation in AF The Standard of Care for Stroke Prevention
Anticoagulation HRS Education 4/14/2017 9:23 PM Warfarin Better Control Better AFASAK SPAF BAATAF CAFA SPINAFa EAFT 100% 50% -50% -100% Aggregate Terminated early Double-blind; men only Unblinded 2o prevention; unblinded Take home point: The use of warfarin results in significant risk reduction. There are some limitations to the clinical trials though. aOnly SPINAF used placebo-controlled, double-blind design; no women included. Hart et al. Ann Intern Med. 2007;146: 13

Effect of Intensity of Oral Anticoagulation on Stroke Severity
Anticoagulation HRS Education 4/14/2017 9:23 PM N=596 patients with AF and ischemic stroke INR<2 INR2 Fatal stroke 9% 1% Severe (total dependence) 6% 4% Major (not independent) 44% 38% Total 59% 43% Minor (independent) 38% 55% No neurologic sequelae 3% 2% Total 41% 57% Take home point: The variability of INR during warfarin therapy is highly problematic. When INR is maintained above 2, the risk of stroke is substantially lower. Hylek et al. N Engl J Med. 2003;349: 14

Underuse of Antithrombotic Therapy in AF
Anticoagulation HRS Education 4/14/2017 9:23 PM 597 Medicare patients with AF; Rx at hospital discharge Warfarin Aspirin Neither Age (years) >75 42% 29% 23% 21% 36% 53% Sex Male Female 38% 29% 22% 21% 42% 51% Location Urban Rural 36% 30% 23% 17% 42% 54% Take home point: Despite the data supporting the use of warfarin, it is underutilized in stroke prevention in AF patients. Gage et al. Stroke. 2000;31: 15

Use and Adequacy of Anticoagulation in AF Patients in Primary Care Practice
Anticoagulation HRS Education 4/14/2017 9:23 PM N=660 INR above target 6% No warfarin 65% Take home point: A significant percent of patients who should receive warfarin do not. Further, those patients that receive warfarin are not always in the therapeutic range, making the effective use of warfarin even lower. This study is in patients in primary care practices. Background: In an attempt to evaluate the quality of anticoagulation management by primary care physicians in an outpatient setting, this retrospective study evaluated the medical records of 660 patients with AF managed by internists and family practitioners. This study found that only 34.7% of patients with AF who met the criteria for anticoagulation received warfarin (65% received no warfarin). Only 15% had their INR within the range of 2 to 3, 13% had INR less than 2, and 6% had an INR greater than 3. INR in target range 15% Subtherapeutic INR 13% Samsa et al. Arch Intern Med. 2000;160: 16

Supratherapeutic INR 19%
Use and Adequacy of Anticoagulation in AF Patients on Hospital Admission Anticoagulation HRS Education 4/14/2017 9:23 PM Supratherapeutic INR 19% No warfarin 64% Take home point: A significant percent of patients who should receive warfarin do not. Further, those patients that receive warfarin are not always in the therapeutic range, making the effective use of warfarin even lower. This study is in patients admitted to the hospital. Background: Despite warfarin’s proven efficacy in preventing ischemic CVA in patients with nonvalvular AF, many patients are not adequately anticoagulated. The reasons for this are 2-fold: warfarin therapy is underused, and despite treatment with warfarin therapy, target INR is not maintained. In a study of 1085 patients admitted to a tertiary care facility who had their INR measured upon arrival at the hospital, only 37% were in therapeutic range; 19% had a supratherapeutic INR and 45% had a subtherapeutic INR. Sixty-four percent of patients with AF arriving at the hospital had not been prescribed warfarin. The underuse and difficulties in management of warfarin diminish the drugs’ effectiveness and have motivated researchers to investigate other methods of anticoagulation. Therapeutic INR 37% Warfarin 35% Subtherapeutic INR 45% Bungard et al. Pharmacotherapy. 2000;20: 17

Anticoagulation With Warfarin Intensity Often Outside the Target Range
Anticoagulation HRS Education 4/14/2017 9:23 PM International Study of Anticoagulation Management 100 INR<2 INR 2–3 INR>3 80 Take home point: Warfarin is a relatively difficult drug to use as noted by the variability in INR in clinical practice. Background: A retrospective, multicenter cohort study, conducted in the US, Canada, France, Italy and Spain, randomly recruited 1511 patients from representative practices (routine medical care in the US, Canada and France and anticoagulation clinics in Italy and Spain). Medical records were used to extract data relating to their oral anticoagulant care. All patients included in this study received oral anticoagulation for at least 60 days. These data show that oral anticoagulation care varied considerably and patients spent less between 50.8% and 60.0% of their time within the target INR of 2–3. The percentage of time within this range varied from 58.1% to 69.5%. The mean time spent in range did not differ by age or sex. 60 % Time in Target Range 40 20 US Canada France Italy Spain Ansell et al. J Thromb Thrombolysis. 2007;23:83-91. 18

Warfarin Use in Patients With AF
Anticoagulation HRS Education 4/14/2017 9:23 PM 100 N=5888 community residents with AF <80 y 80 y 90 80 70 60 Percentage Use 50 Take home point: A significant underuse of warfarin is seen especially in the elderly patients who stand to gain the most from stroke prevention in terms or stroke risk. 40 30 20 10 n=110 n=34 n=79 n=32 n=80 n=34 n=83 n=36 n=78 n=38 n=73 n=57 n=72 n=63 Examination Year Smith et al. Arch Intern Med. 1999;159: 19

The Challenge of Nonadherence to Guidelines for AF Treatment
Anticoagulation HRS Education 4/14/2017 9:23 PM AF has the highest prevalence in the elderly The elderly are at the highest risk for stroke Thus, the elderly are most likely to benefit from anticoagulation; however, they are the least likely to receive anticoagulation Take home point: Elderly patients will have the greatest stroke risk reduction with the use of warfarin but are least likely to receive it due to perceived risks of bleeding. 20

Physician Questionnaire Results on AF and Warfarin
Anticoagulation HRS Education 4/14/2017 9:23 PM No relationship between perceived benefits of warfarin and its use Perceived risk for hemorrhage strongly inversely associated with warfarin use (P<.001) Estimated annual rates of warfarin-associated hemorrhage >10- fold higher than literature-based estimates Physician attitudes reflect aversion to hemorrhagic risk that influences responses to treatment recommendations Take home point: Further education is needed to impact physician perception of anticoagulation in AF. Background: Another more recent study also attempted to determine physicians’ perceptions regarding warfarin use in patients with AF. In this study, a cross-section of 426 general internists were randomly selected from a national pool of American Medical Association (AMA) physicians to receive a self-administered survey that included 14 clinical case vignettes. The surveys included scenarios of varying comorbidities and risk factors for major bleeding or CVA. The outcome measure was the number of case vignettes in which physicians chose to use warfarin. Thirty-three percent of the physicians polled responded. The median number of case vignettes in which warfarin was deemed appropriate was 10 (interquartile range, 8-12). Following analysis of the surveys, the study found no relationship between perceived benefit of warfarin and its use in the case vignettes provided. However, a relationship between perceived risk of warfarin-associated hemorrhage and warfarin use was determined (P<.001). Respondents also estimated that the annual rate of warfarin-associated ICH was greater than 10-fold higher than estimates found in the literature, and physicians who provided higher risk estimates were less likely to use warfarin therapy. In addition, physicians who found warfarin utilization warranted and recommended its use were less likely to report anticipated regret of committing an error of omission (P<.001) or a loss-aversive risk preference (P<.027). In addition, these physicians reported a lower perceived risk for hemorrhage (P<.001). The study concluded that warfarin usage is generally not determined by perceived benefit. However, perceived risk of bleeding does appear to be a driving force in choosing warfarin as therapy for stroke prevention in patients with AF. Furthermore, the perceived risk of anticoagulation is greatly overestimated. Gross et al. Clin Ther. 2003;25: 21

Physician Concerns About Warfarin for Stroke Prevention in AF
Anticoagulation HRS Education 4/14/2017 9:23 PM Risk vs benefit of warfarin 47% benefit greatly outweigh risk 34% risk slightly outweigh benefit 19% risk outweigh benefit Percent Take home point: Physicians are reluctant to use warfarin for fear of bleeding risk. The risk/benefit ratio of warfarin must be clearly evaluated. Background: In order to determine physician perceptions of warfarin usage for stroke prevention in AF populations, 269 primary care physicians across 30 long-term care facilities in New England, Quebec, and Ontario were asked to complete a questionnaire on the use of warfarin therapy as a tool for stroke prevention. Two clinical scenarios were included in the survey. The intention was to provide 2 hypothetical patient situations that varied according to patient characteristics, comorbidities, functional status, bleeding risk, and stroke. Approximately 68% of the physicians polled responded. Of these, only 47.7% believed that the benefits of warfarin “greatly outweigh the risks” and 34% and 19% believed that the risks “slightly outweigh the benefits” or “outweigh the benefits,” respectively. Physicians were also asked to indicate the most frequent contraindications to warfarin use. These were excessive risk of falls and history of GI bleeding, which were both cited 71% of the time, followed by history of other non–central nervous system (CNS) bleeding (36%), and history of cardiovascular hemorrhage (25%). The study concluded that physicians perceive many uncertainties regarding the use of warfarin therapy in stroke prevention and concerns regarding bleeding risk seem to prevail over stroke prevention when making a decision regarding therapy. History of GI Bleed Risk of Fall History of Non-CNS Bleed History of CV Hemorrhage Frequently Cited Contraindications Monette et al. J Am Geriatr Soc. 1997;45: 22

Patient Concerns About AF
Anticoagulation HRS Education 4/14/2017 9:23 PM 91% 38% Percent Take home point: Patients fear a stroke more than death. Background: In this study, patients with nonvalvular AF were interviewed to determine the smallest difference associated with a therapy that patients perceive as beneficial enough to mandate a change in management, despite cost inconvenience and adverse effects. Patients identified fear of stroke as, by far, the greatest factor that affected their decision-making process. Death, major bleeding, and minor side effects were less frequently identified. In fact, many patients found stroke worse than death. 13% 9% 5% 2% Minor Side Effects Stroke Major Bleeding Cost Inconvenience Death Man-Son-Hing et al. Arch Intern Med. 1996;156: 23

Patient Perceptions of AF and Anticoagulation
Anticoagulation HRS Education 4/14/2017 9:23 PM 61% felt that AF was not serious 47% unaware that AF predisposed to stroke 52% aware of reason for warfarin 45% believed some risk associated with warfarin 42% stated they were “careless” at times about taking warfarin Take home point: Patients are unaware of the seriousness of stroke risk in AF. This may translate to less than optimal use of warfarin. Background: Active patient participation is crucial to appropriate compliance and management of warfarin therapy. In this study, 119 patients with AF in anticoagulation clinics in Birmingham, United Kingdom, were surveyed to investigate the level of knowledge and perceptions regarding AF and antithrombotic therapy. Overall, 63% of patients were aware of their cardiac condition as “atrial fibrillation” or “fast/irregular heart rate/rhythm/palpitation.” The majority (61%) felt that AF was not serious and 47% were not aware that it predisposed to stroke. Only one half of patients were aware of the reason for anticoagulation and the other half were utilizing warfarin simply because their doctor told them to do so. More than half were not aware of any specific risks associated with warfarin therapy. Of greatest concern was that approximately half of all patients said they were careless at times about taking their warfarin therapy and only about half felt that their physician had given them enough information. Lip et al. Stroke. 2002;33: 24

ACC/AHA/ESC Guidelines General Considerations for Anticoagulation in AF
Anticoagulation HRS Education 4/14/2017 9:23 PM Anticoagulation therapy is the only therapy in AF that has demonstrated mortality reduction As a group, patients with AF are 6 times more likely to sustain stroke compared with patients in SR Risk of stroke varies with risk factors, and decisions regarding anticoagulation should be based on stroke risk Patients treated with rhythm control strategy are still at risk for stroke—anticoagulation cannot be discontinued indiscriminately Anticoagulation guidelines apply to AF and atrial flutter equally Take home point: These are the general considerations for anticoagulant use in AF. This slide mixes recommendations based on widely different levels of evidence. The statement about atrial flutter, for instance, is based on little substantive evidence. Fuster et al. J Am Coll Cardiol. 2006;48: 25

Risk vs Benefit in Anticoagulation
Anticoagulation HRS Education 4/14/2017 9:23 PM Estimating risk of stroke for each individual is crucial for anticoagulation decision Risk threshold warranting anticoagulation is controversial, but most accept 2%-3% risk/year NNT for ≤2%/year = 100 or more NNT for ≥6%/year = 25 or less Controversy is greatest in 3%-5% risk categories Several risk stratification schemes exist: AF Investigators, SPAF, Framingham, CHADS2 Take home point: Stroke risk warranting anticoagulation is usually accepted to be around 2-3% per year. There are numerous risk assessment schemes. Fuster et al. J Am Coll Cardiol. 2006;48: 26

Risk Factors for Stroke and Systemic Embolism
Anticoagulation HRS Education 4/14/2017 9:23 PM Risk Factors Relative Risk Previous stroke or TIA 2.5 Diabetes mellitus 1.7 History of hypertension 1.6 Heart failure 1.4 Advanced age (continuous, per decade) Take home point: These are significant risk factors for stroke with prior stroke carrying a 2.5x relative risk. This is therefore the background for the CHADS2 risk scoring system. Data derived from collaborative analysis of 5 untreated control groups in primary prevention trials. TIA=transient ischemic attack. Fuster et al. J Am Coll Cardiol. 2006;48: 27

CHADS2 Risk Stratification Scheme
Anticoagulation HRS Education 4/14/2017 9:23 PM Risk Factors Score C Recent congestive heart failure 1 H Hypertension A Age 75 years D Diabetes mellitus S2 History of stroke or transient ischemic attack 2 Take home point: It is critical to apply a risk scheme to quantify risk for stroke in AF. The CHADS2 scoring system is commonly used by several different guidelines and represents the current recommendation for stroke risk assessment of the ACC/AHA/ESC guidelines for the management of AF. Background: Several risk stratification schemes currently exist to aid physicians in selecting appropriate antithrombotic therapy for patients with AF. In order to assess the quality of such tools, 2 current and 1 new classification scheme (CHADS2) were assessed for their predictive value. The CHADS2 combined conclusions and recommendations from the AFI and the SPAF Investigators to create a scheme that assigned point values to comorbidities. The points are totaled to create the score. The CHADS acronym refers to the comorbidities it assesses and assigns a point value based on the risk factor. The C refers to recent CHF, the H stands for hypertension, A stands for age 75 or greater, and D is for diabetes, each of which receives 1 point. Two points are assigned for history of stroke or TIA. Patients are assessed for these risk factors and the total provides a guideline for risk and management of a patient. For example, a patient with recent CHF and diabetes would receive a score of 2 and would fall into the moderate-risk category. However, a patient who only has hypertension would have a score of 1. EP: Progress Indicators 1. Awareness of the existence of the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation. (knowledge) 2. Calculate a CHADS2 risk score for assessment of stroke risk in patients with nonvalvular atrial fibrillation. (performance) Learning Objectives 1. Outline the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation (AF) and calculate a CHADS2 risk score for such patients [Progress Indicators 1, 2] Instructional Objectives 1. Presented with clinical information for a patient with nonvalvular AF, participants will be able to identify the CHADS2 risk index as an appropriate assessment tool to determine stroke risk. 2. Given pertinent patient information, participants will be able to calculate a CHADS2 risk score for a patient with nonvalvular AF. CARD: Progress Indicators PCP: 1. Outline the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation (AF) [Progress Indicator 1] 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] Rockson et al. J Am Coll Cardiol. 2004;43: 28

The CHADS2 Index Stroke Risk Score for AF
Anticoagulation HRS Education 4/14/2017 9:23 PM Score (points) Prevalence (%) Prior stroke or TIA 2 10 Age >75 years 1 28 Hypertension 65 Diabetes mellitus 18 Heart failure 32 High risk 3 22 Moderate risk 1-2 33-50 Low risk 0-1 18-51 Take home point: It is critical to apply a risk scheme to quantify risk for stroke in AF. The CHADS2 scoring system is commonly used by several different guidelines and represents the current recommendation for stroke risk assessment of the ACC/AHA/ESC guidelines for the management of AF. Background: Several risk stratification schemes currently exist to aid physicians in selecting appropriate anithrombotic therapy for patients with AF. In order to assess the quality of such tools, 2 current and 1 new classification scheme (CHADS2) were assessed for their predictive value. The CHADS2 combined conclusions and recommendations from the Atrial Fibrillation Investigators (AFI) and the SPAF Investigators to create a scheme that assigned point values to comorbidities. The points are totaled to create the score. The CHADS acronym refers to the comorbidities it assesses: CHF, hypertension, age 75 or greater, and diabetes, each of which receives 1 point. Two points are assigned for history of stroke or TIA. The study of these schemes included 2121 patient-years of follow-up with an outcome measure of hospitalization for ischemic stroke, which was determined by Medicare claims data. According to assessment of patient comorbidities, scores were correlated to adjusted stroke rates. These are outlined in the chart on this slide. The adjusted stroke rate is the expected rate of stroke per 100 patient-years. These scores also correlated to varying risk levels that range from low (scores 0-1) to high (scores 4-6). Based on assessment, both the AFI and SPAF Investigators’ schemes were determined to be viable tools for physician use. However, the CHADS2 was found to be more accurate at predicting stroke than the 2 established methods. The study concluded that both the existing and the new CHADS2 schemes can quantify the risk of stroke in AF patients and, therefore, may be useful tools for physicians when determining appropriate anticoagulation therapy in AF patients. van Walraven et al. Arch Intern Med. 2003;163: ; Nieuwlaat et al. Euro Heart Survey. Eur Heart J (Epub). EP: Progress Indicators 1. Awareness of the existence of the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation. (knowledge) 2. Calculate a CHADS2 risk score for assessment of stroke risk in patients with nonvalvular atrial fibrillation. (performance) 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) Learning Objectives 1.Outline the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation (AF) and calculate a CHADS2 risk score for such patients [Progress Indicators 1, 2] 2.Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] Instructional Objectives 1. Presented with clinical information for a patient with nonvalvular AF, participants will be able to identify the CHADS2 risk index as an appropriate assessment tool to determine stroke risk. 2. Given pertinent patient information, participants will be able to calculate a CHADS2 risk score for a patient with nonvalvular AF. 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. CARD: PCP: 1. Outline the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation (AF) [Progress Indicator 1] 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for preventing stroke. JAMA. 2001;285: Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med. 2003;139: 29

CHADS2 Risk Criteria for Stroke in Nonvalvular AF
Anticoagulation HRS Education 4/14/2017 9:23 PM Stroke Risk in Patients With Nonvalvular AF Not Treated With Anticoagulation According to the CHADS2 Index Patients (N=1733) CHADS2 Score (95% CI) 120 463 1 523 2 Warfarin Take home point: It is critical to apply a risk scheme to quantify risk for stroke in AF. The CHADS2 scoring system is commonly used by several different guidelines and represents the current recommendation for stroke risk assessment of the ACC/AHA/ESC guidelines for the management of AF. It correlates well to the risk of stroke. 337 3 220 4 65 5 EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) Learning Objectives 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. CARD: Progress Indicator Learning Objective PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 5 6 Adjusted Stroke Rate (%/y) Fuster et al. J Am Coll Cardiol. 2006;48: 30

Stroke Risk in New-Onset AF ACP/AAFP Guidelines
Anticoagulation HRS Education 4/14/2017 9:23 PM CHADS2a Score Adjusted Stroke Rateb (95% CI) CHADS2 Risk Level 1.9 ( ) Low 1 2.8 ( ) 2 4.0 ( ) Moderate 3 5.9 ( ) 4 8.5 ( ) High 5 12.5 ( ) 6 18.2 ( ) Take home point: It is critical to apply a risk scheme to quantify risk for stroke in AF. The CHADS2 scoring system is commonly used by several different guidelines and represents the current recommendation for stroke risk assessment of the ACC/AHA/ESC guidelines for the management of AF. Background: Several risk stratification schemes currently exist to aid physicians in selecting appropriate anithrombotic therapy for patients with AF. In order to assess the quality of such tools, 2 current and 1 new classification scheme (CHADS2) were assessed for their predictive value. The CHADS2 combined conclusions and recommendations from the Atrial Fibrillation Investigators (AFI) and the SPAF Investigators to create a scheme that assigned point values to comorbidities. The points are totaled to create the score. The CHADS acronym refers to the comorbidities it assesses: CHF, hypertension, age 75 or greater, and diabetes, each of which receives 1 point. Two points are assigned for history of stroke or TIA. The study of these schemes included 2121 patient-years of follow-up with an outcome measure of hospitalization for ischemic stroke, which was determined by Medicare claims data. According to assessment of patient comorbidities, scores were correlated to adjusted stroke rates. These are outlined in the chart on this slide. The adjusted stroke rate is the expected rate of stroke per 100 patient-years. These scores also correlated to varying risk levels that range from low (scores 0-1) to high (scores 4-6). Based on assessment, both the AFI and SPAF Investigators’ schemes were determined to be viable tools for physician use. However, the CHADS2 was found to be more accurate at predicting stroke than the 2 established methods. The study concluded that both the existing and the new CHADS2 schemes can quantify the risk of stroke in AF patients and, therefore, may be useful tools for physicians when determining appropriate anticoagulation therapy in AF patients. Warfarin a Assessment of the following comorbidities: CHF, hypertension, age ≥75, and diabetes (1 point each); history of stroke or TIA (2 points each). b Expected rate of stroke per 100 patient-years. Snow et al. Ann Intern Med. 2003;139: EP: Progress Indicators 2. Calculate a CHADS2 risk score for assessment of stroke risk in patients with nonvalvular atrial fibrillation. (performance) 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) Learning Objectives 1.Outline the CHADS2 risk index for assessment of stroke risk in patients with nonvalvular atrial fibrillation (AF) and calculate a CHADS2 risk score for such patients [Progress Indicators 1, 2] 2.Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] Instructional Objectives 2. Given pertinent patient information, participants will be able to calculate a CHADS2 risk score for a patient with nonvalvular AF. 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. CARD: PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for preventing stroke. JAMA. 2001;285: Snow V, Weiss KB, LeFevre M, et al. Management of newly detected atrial fibrillation: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med. 2003;139: 31

Will need to update when new ACCP guidelines are published in early 08
Current Recommendations for Stroke Prevention in AF American College of Chest Physicians Guidelines Anticoagulation HRS Education 4/14/2017 9:23 PM Risk Category Goal INR Comment Age <65 years, no other risk factors None Aspirin 325 mg qd Age years, no other risk factors 2.5 ( ) Warfarin or aspirin 325 mg qd Any high-risk factor Warfarin High-risk factors: previous TIA, systemic embolism, or stroke; HTN, LV dysfunction, and/or recent CHF; age >75 years; DM; rheumatic heart disease (mitral stenosis); and prosthetic heart valve Will need to update when new ACCP guidelines are published in early 08 Take home point: Other criteria also exist for risk stratification and anticoagulation recommendations. This represents the scheme from ACCP Chest. Singer et al. Chest. 2004;126(3 suppl):429S-456S. 32

Risk-Based Approach to Antithrombotic Therapy
Anticoagulation HRS Education 4/14/2017 9:23 PM Patient Features Antithrombotic Therapy Class of Recommendation Age <60 y, no HD (lone AF) ASA ( mg/d) or no therapy I Age <60 y, HD but no risk factorsa ASA (81 to 325 mg/d) Age y, no risk factorsa ASA (81 to 325 mg per day) Age y with DM or CAD OAC (INR 2.0 to 3.0) Age ≥75 y, women Age ≥75 y, men, no other risk factors OAC (INR ) or ASA ( mg/d) Age ≥65, HF OAC (INR ) LVEF <35% or fractional shortening <25%, and hypertension Rheumatic HD (mitral stenosis) Prosthetic heart valve OAC (INR or higher) Prior thromboembolism Persistent atrial thrombus on TEE IIa For library only Take home point: The recommendations of the ACC/AHA/ESC guidelines are generally class I recommendations. aRisk factors for thromboembolism include heart failure (HF), left ventricular ejection fraction (LVEF) less than 35%, and history of hypertension. Fuster et al. J Am Coll Cardiol. 2006;48: 33

Risk Stratification in AF: Stroke Risk Factors
Anticoagulation HRS Education 4/14/2017 9:23 PM High-Risk Factors Mitral stenosis Prosthetic heart valve History of stroke or TIA Moderate-Risk Factors Age >75 years Hypertension Diabetes mellitus Heart failure or ↓ LV function Take home point: This slide depicts risk factors for stroke from the most recent guidelines on prevention of stroke in patients with AF from the ACCP. Background: ACCP guidelines also suggest that women with AF who are older than 75 years may be at an increased risk of stroke compared with men of the same age. The impact of gender on risk of stroke in patients with AF has not been definitively determined. Increasing age is a risk factor for stroke in patients with AF, regardless of gender. Recently, a joint committee representing the American College of Cardiology (ACC), AHA, and European Society of Cardiology (ESC) published guidelines on the management of patients with AF. This document identifies the same risk factors for stroke in patients with AF as the ACCP guidelines, with the addition of persistent thrombus on transesophageal echocardiography (TEE) and thyrotoxicosis as risk factors. Less Validated Risk Factors Age years Coronary artery disease Female gender Thyrotoxicosis Singer et al. Chest. 2004;126:429S-456S; Fang et al. Circulation. 2005;112: 34

ACC/AHA/ESC Guidelines
Anticoagulation HRS Education 4/14/2017 9:23 PM Warfarin (INR range 2-3) Women age 75 years Age 65 to 74 years with DM or CAD LVEF <35% or fractional shortening <25%, and HTN Age 65 years, HF Rheumatic heart disease (mitral stenosis) Warfarin (INR range 2-3, or higher) Prosthetic heart valve Prior thromboembolism Persistent atrial thrombus on TEE Warfarin (INR range 2-3) with optional addition of aspirin ( mg) Men age 75 years with no other risk factors For library only Take home point: The above slide outlines the ACC/AHA/ESC guidelines for the use of warfarin and aspirin in the treatment of patients with AF. Broken down by target INR range for warfarin and dosage range for aspirin, the guidelines establish the ideal treatment, taking into account varying patient characteristics including age, history, and comorbidities. Fuster et al. J Am Coll Cardiol. 2006;48: 35

ACC/AHA/ESC Guidelines
Anticoagulation HRS Education 4/14/2017 9:23 PM Aspirin ( mg) Age <60 years, heart disease but no risk factors Age years, no risk factors Aspirin ( mg) or no treatment Age <60 years, no heart disease (lone AF) For library only Take home point: The above slide outlines the ACC/AHA/ESC guidelines for the use of warfarin and aspirin in the treatment of patients with AF. Broken down by target INR range for warfarin and dosage range for aspirin, the guidelines establish the ideal treatment, taking into account varying patient characteristics including age, history, and comorbidities. Fuster et al. J Am Coll Cardiol. 2006;48: 36

Antithrombotic Therapy for Patients With AF
Anticoagulation HRS Education 4/14/2017 9:23 PM Risk Category Recommended Therapy No risk factors Aspirin, 81 to 325 mg daily One moderate-risk factor Aspirin, 81 to 325 mg daily, or warfarin (INR 2.0 to 3.0, target 2.5) Any high-risk factor or more than 1 moderate-risk factor Warfarin (INR 2.0 to 3.0, target 2.5)a Less Validated or Weaker Risk Factors Moderate-Risk Factors High-Risk Factors Female sex Age 65 to 74 years Coronary artery disease Thyrotoxicosis Age 75 years Hypertension Heart failure LV ejection fraction 35% or less Diabetes mellitus Previous stroke, TIA, or embolism Mitral stenosis Prosthetic heart valvea Take home point: These are the recommendations for anticoagulation and represent the current recommendation for stroke risk assessment of the ACC/AHA/ESC guidelines for the management of AF. aIf mechanical valve, target international normalized ratio (INR) greater than 2.5. LV=left ventricular. Fuster et al. J Am Coll Cardiol. 2006;48: 37

Special Considerations for Anticoagulation Prior to Cardioversion
Anticoagulation HRS Education 4/14/2017 9:23 PM For patients with AF of ≥48 hours of AF, or when duration is unknown, 3 weeks of anticoagulation with documented INR ≥ 2 are required prior to cardioversion It may take longer than 3 weeks to achieve 3 consecutive weeks of adequate (INR ≥ 2) anticoagulation Anticoagulation must be continued for at least 4 weeks post cardioversion TEE can be used to assess LA for thrombus as alternative to 3-week anticoagulation (however, anticoagulation must continue for 4 weeks post cardioversion) Take home point: Anticoagulation is not always consistent and therefore 3 weeks of anticoagulation may take longer than 3 weeks. Fuster et al. J Am Coll Cardiol. 2006;48: 38

Confirmed Embolism (%) INR at Time of Cardioversion
Relation Between INR on the Day of Cardioversion and Risk of Thromboembolism Anticoagulation HRS Education 4/14/2017 9:23 PM 4 N=1950 1/42 3 2/182 4/530 Confirmed Embolism (%) 2 Take home point: Careful control of adeuqate INR is critical to minimize risk of stroke for cardioversion. Background: This retrospective study reviewed the case records of 1950 patients who underwent direct current cardioversion in an attempt to evaluate the factors responsible for embolic complications. The study found that the risk of embolism in patients is significantly higher in those whose INR was less than 2.5 at the time of the procedure. Of note, the sampling of the INR used for correlation was done on the day of cardioversion. It is possible that the lower levels of anticoagulation are associated with periods of undercoagulation during the time leading up to cardioversion. It is important to determine that anticoagulation has been satisfactory during the 3 weeks prior to cardioversion, not only on the day of cardioversion. 1 0/779 1-1.4 2-2.4 >2.4 INR at Time of Cardioversion Gallagher et al. J Am Coll Cardiol. 2002;40: 39

Prevalence of Atrial Thrombus With Transiently Subtherapeutic INR
Anticoagulation HRS Education 4/14/2017 9:23 PM 182 consecutive patients with AF and subtherapeutic INR on 2 measurements in the last 3 weeks before the scheduled cardioversion Intra-atrial thrombus in 18 (9.9%) None (0%) of 21 with LA dimension 4.0 cm 11.2% with dilated LA No difference in LVEF Take home point: It is critical to ensure adequate anticoagulation prior to cardioversion. Background: Standard therapy prior to cardioversion is warfarin with a target INR of 2 to 3 given continuously for 3 to 4 weeks. However, maintenance of target INR often can be difficult. Therefore, Shen et al sought to determine if episodes of subtherapeutic warfarin given for more than 3 weeks was associated with persistence of thrombi. The incidence of intra-atrial clots was assessed in AF patients. Patients were deemed to have received subtherapeutic treatment if INR was less than 2 during 2 or more measurements taken at various points of the 3-week period. One hundred eighty-two patients with subtherapeutic INR underwent TEE. Atrial thrombi were detected in 18 patients (10%). None of the 21 patients with LA diameter of less than 4 cm had an atrial thrombus and 11.2% of patients with LA of greater than 4 cm had an atrial thrombus. In addition, LA diameter was significantly larger in patients with a thrombus than without (P<.05). The study found that a single subtherapeutic INR 1 week before TEE did not predict absence of a thrombus. Investigators concluded that subtherapeutic INR treatment had the same risk of thrombus as no treatment with anticoagulation. Shen. J Am Coll Cardiol. 2002;39(suppl):376A-377A. 40

Anticoagulation Variability Prior to Cardioversion
Anticoagulation HRS Education 4/14/2017 9:23 PM Time to Subtherapeutic INR After the First Therapeutic Value Take home point: Prior to elective cardioversion, anticoagulation for 3 weeks is necessary. Background: Adequate anticoagulation is defined as and INR ≥2.0 during those 3 weeks. In this study, a retrospective analysis of 59 patients undergoing elective cardioversion was conducted. Patients who did not undergo cardioversion due to subtherapeutic INR on the day of cardioversion were excluded. The study revealed that 42.4% of patients had subtherapeutic INR values after the first therapeutic INR was documented. Most of these episodes occurred by day 15 and 73% occurred by day 30. These episodes resulted in delays to cardioversion. Number of Patients Days (midpoint) to Subtherapeutic INR Kim et al. Am J Cardiol. 2001;88: 41

Achieving Adequate Anticoagulation Prior to Cardioversion
Anticoagulation HRS Education 4/14/2017 9:23 PM n (interquartile range) INR checks 9 (6-11) Days to 1st therapeutic INR 7 (4-15) Days to 3 weeks therapeutic INR 35 (27-47) Days to cardioversion 58 (41-78) Take home point: Prior to elective cardioversion, anticoagulation for 3 weeks is necessary. Background: Adequate anticoagulation is defined as and INR ≥2.0 during those 3 weeks. In this study, a retrospective analysis of 59 patients undergoing elective cardioversion was conducted. Patients who did not undergo cardioversion due to subtherapeutic INR on the day of cardioversion were excluded. The study revealed that 42.4% of patients had subtherapeutic INR values after the first therapeutic INR was documented. Those patients who developed a subtherapeutic INR also had a delay of cardioversion (48 days) versus those without this episode (78 days, p<0.002). The overall time to cardioversion was 58 days, indicating that although, ideally, cardioversion can be performed 3 weeks after initiation of anticoagulation, delays occur in clinical practice due to the difficulty in achieving and maintaining 3 weeks of anticoagulation. Kim et al. Am J Cardiol. 2001;88: 42

Warfarin Dosing and Genomics
Anticoagulation HRS Education 4/14/2017 9:23 PM 10 CYP2C9 = *1/*2 Daily Dose (mg/day) 2 4 6 8 10 1 3 5 7 9 40 45 50 55 60 65 70 75 80 85 Age (years) CG GG CC 9 CG GG CC CYP2C9 = *1/*1 8 7 6 Daily Dose (mg/day) 5 4 3 2 1 Take home point: Warfarin can be dosed based on patient genetics. Some drugs already have FDA labeling instructing dosing based on genomics. 40 45 50 55 60 65 70 75 80 85 Age (years) CYP2C9 = *1/*3 Daily Dose (mg/day) 2 4 6 8 10 1 3 5 7 9 40 45 50 55 60 65 70 75 80 85 CG GG CC Caldwell et al. Clin Med Res. 2007;5:8-16. Age (years) 43

Unanswered Questions About Anticoagulation in Patients Restored to SR
Anticoagulation HRS Education 4/14/2017 9:23 PM Does restoration of sinus rhythm prevent stroke in patients with AF? What is the duration of anticoagulation in patients maintained in SR? How should one determine efficacy of maintenance? Take home point: There are still some outstanding issues where more data is required. 44

Stroke Rates in AFFIRM In AFFIRM, there were 157 ischemic strokes
Anticoagulation HRS Education 4/14/2017 9:23 PM In AFFIRM, there were 157 ischemic strokes At the time of stroke, only 53.5% of patients assigned to rate control and 30.8% of those assigned to rhythm control were in AF Take home point: Strokes in patients in the AFFIRM study occurred in patients in AF but also in patients in SR. 45

Rhythm or Rate Control in AF Evidence Base
Anticoagulation HRS Education 4/14/2017 9:23 PM 4 Randomized Trials Comparing 2 Treatment Strategies PIAF Pharmacological Intervention in Atrial Fibrillation (pilot) STAF Strategies of Treatment of Atrial Fibrillation (pilot) AFFIRM Atrial Fibrillation Follow-up Investigation of Rhythm Management RACE RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Take home point: Trials compared rate versus rhythm strategies, but important finding were regarding anticoagulation. The AFFIRM Investigators. N Engl J Med. 2002;347: ; Carlsson et al. J Am Coll Cardiol. 2003;41: ; Gronefeld. Card Electrophysiol Rev. 2003;7: ; Van Gelder et al. N Engl J Med. 2002;347: 46

Rate Control vs Electrical Cardioversion for Persistent AF (RACE) Study
Anticoagulation HRS Education 4/14/2017 9:23 PM 522 patients with persistent AF/AFl 24 hours to 1 year randomized to rate vs rhythm control Rate control to resting rate <100 bpm Rhythm control with electrical cardioversion and serial antiarrhythmics Follow-up 2 years Primary end point: composite of death from cardiovascular events Take home point: RACE was a rate versus rhythm strategy trial. Background: The RACE Study (Rate Control verus Electrical Cardioversion for Persistent AF) was a randomized, prospective study comparing the long term effects of rate control versus rhythm control, using electrical cardioversion for persistent AF. 522 patients with persistent AF or atrial flutter who had undergone pervious cardioversion were randomly assigned to received treatment aimed at rate control or rhythm control. Patients were excluded from the study if the arrhythmia had lasted longer than one year. The target resting heart rate in the rate control group was less than 100 bpm. Rate control was achieve via the administration of digitalis, a nonhydropyridine calcium channel blocker, and a beta blocker, a lone or in combination. The rhythm control group underwent electrical cardioversion and were subsequently treated with sotalol. These patients were subsequently treated with flecainide or propafenone after cardioversion, if the arrhythmia recurred. If the patients again experienced a recurrence of AF, they underwent cardioversion after receiving a loading dose of amiodarone. All patients who underwent cardioversion were anticoagulated beginning four weeks prior to the procedure until four weeks after the procedure. The target INR was Patients were followed for a mean of 2.3 years. Primary endpoints of the study were the composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, the need for pacemaker implantation or severe antiarrhythmic drug side effects. Van Gelder et al. N Engl J Med. 2002;347: 47

RACE: Stroke Rates Thromboembolic events in 35/522 (6.7%)
Anticoagulation HRS Education 4/14/2017 9:23 PM Thromboembolic events in 35/522 (6.7%) 5.5% of rate control 7.9% of rhythm control 6 patients had events after cessation of warfarin 5 of these patients were in SR 23/35 (68%) had events while taking warfarin with INR <2.0 17/21 (81%) bleeding episodes occurred with INR >3.0 Take home point: Stroke rates occurred in the rhythm control arm in patients who had anticoagulation discontinues and had strokes despite the fact that the patient was in SR. INR values varied and events were documented during out of range values. Background: The results of the RACE study included findings on thromboembolic complications in both the rate- and rhythm-control groups. During follow-up the number of patients taking oral anticoagulant therapy varied, but remained high in both arms with a range of 246 (96%) to 254 (99%) for the rate-control group and 228 (86%) to 263 (99%) in the rhythm-control group. As the slide illustrates, the rate of thromboembolic events was higher in the rhythm-control group, with 5.5% in the rate control and 7.9% in the rhythm control. When the events in the rhythm-control group were broken down, the findings showed that 6 patients had events after discontinuation of warfarin therapy, of those 6, 5 patients were in SR. The intensity of warfarin therapy also showed an effect on thromboembolic events with 23 events (4.4%) occurring in patients treated with warfarin therapy lower than an INR of 2.0. Seventy-three percent of patients were in AF at the time of a thromboembolic event. The investigators theorize that the high incidence of stroke was due to the high number of patients with stroke risk factors. Bleeding also seemed to be affected by INR intensity. Of the 21 bleeding events that occurred, 95% of bleeding was found in patients taking anticoagulants. However, 81% of these episodes happened in patients receiving warfarin at an INR >3.0. Although it is a general belief that maintaining SR reduces stroke risk, in patients who have risk factors for stroke, termination of anticoagulants may pose a high risk for stroke. This was based on the fact that 17.1% of the total thromboembolic episodes occurred after anticoagulant therapy had been discontinued, and in all cases but 1, the patients were still in SR. Van Gelder et al. N Engl J Med. 2002;347: 48

Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study
Anticoagulation HRS Education 4/14/2017 9:23 PM Long-term treatment of chronic and paroxysmal AF Patients 65 years old or other risk factor for stroke with AF 6 hours in last 6 months Not continuous AF for 6 months 1 episode documented by ECG in last 12 weeks 1 risk factor for stroke (age 65) Randomized to rate vs rhythm control Both groups anticoagulated Take home point: AFFIRM was a rate versus rhythm strategy trial, but gave substantial information regarding the need for anticoagulation. Background: The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study compared the effect of rhythm control vs rate control of atrial fibrillation. The goal of rhythm control is to diminish the ventricular response rate either using AV nodal blocking agents or with ablation of the AV nodal junction and pacemaker implantation. This was a randomized, multicenter study comparing these two treatment modalities in patients with atrial fibrillation and a high risk of stroke or death. The primary endpoint of the study was overall mortality. Study participants were a minimum of 65 years of age with one or more other risk factors for stroke. Patients had either chronic or paroxysmal atrial fibrillation. Atrial fibrillation had to have lasted six or more hours in the last six months, and one or more episodes documented by ECG in the preceding 12 weeks. All patients in the study were anticoagulated and could not have any contraindications to anticoagulant therapy. The AFFIRM Investigators. N Engl J Med. 2002;347: ; Waldo. Am J Cardiol. 1999; 84: 49

AFFIRM: Stroke Rates 74% of all strokes were ischemic
Anticoagulation HRS Education 4/14/2017 9:23 PM 74% of all strokes were ischemic 44% occurred after warfarin discontinuation 28% taking warfarin, but INR <2.0 42% occurred during AF Take home point: Nearly ¾ of all strokes were related to discontinuation or inadequate anticoagulation. Background: The percentage of patients receiving warfarin therapy was not as high in the AFFIRM study compared with RACE. The use of anticoagulants remained high in the rate-control group at each assessment (85%). However, there was a decrease in warfarin use in the rhythm-control group following the first 4 months of the study. However, the overall number of patients averaged approximately 70% throughout the trial in the rhythm-control group. The majority of patients taking warfarin therapy, regardless of randomization, fell into the recommended INR range of 2.0 to 3.0. Although the rate of ischemic stroke across both groups was low, approximately 1% per year, 74% of all strokes were ischemic. However, strokes tended to occur most often in patients who had ceased to take warfarin or who had a subtherapeutic INR. As the slide illustrates, 44% of ischemic strokes occurred following termination of warfarin therapy and 28% with an INR of less than 2.0. Only 42% of ischemic strokes occurred while a patient was still in AF. There was no significant difference between the 2 groups in rate of ischemic stroke: 5.5% in the rate-control arm and 7.1% in the rhythm-control arm. There was also no significant difference in the percentage of patients with ischemic stroke, primary intracerebral hemorrhage, subdural or subarachnoid hemorrhage, or disabling anoxic encephalopathy. The AFFIRM Investigators. N Engl J Med. 2002;347: 50

Time-Dependent Covariates Associated With Survival
AFFIRM Results Anticoagulation HRS Education 4/14/2017 9:23 PM Time-Dependent Covariates Associated With Survival Covariate P Value Hazard Ratio 99% CI Sinus rhythm <.0001 0.53 Warfarin use 0.50 Digoxin use .0007 1.42 AAD use .0005 1.49 Take home point: The use of warfarin improved survival. HR <1.00: decreased risk of death. HR >1.00: increased risk of death. Epstein. Presented at the American Heart Association’s Scientific Sessions November 2003; Orlando, FL. 51

AFFIRM and RACE Conclusions
Anticoagulation HRS Education 4/14/2017 9:23 PM Trials were to compare end points in rate control vs rhythm control One hypothesis was that sinus rhythm will reduce the stroke rate Critical finding was that rhythm control did not protect from stroke, even though patients were thought to be in SR Patients may have paroxysms of AF that go undetected Take home point: Critical information from AFFIRM and RACE was related to the need for anticoagulation even in patients in SR. Background: AF can be managed in one of two ways, rate control or rhythm control. The rate control strategy involves controlling the ventricular response rate of AF either with the use of AV nodal blocking agents or with ablation of the atrioventricular junction and pacemaker implantation. The rhythm control strategy is directed at returning the patients to SR by electrical cardioversion with subsequent maintenance with antiarrhythmic drugs. One of the rationales for the rhythm control approach was that SR carries with it a lower incidence of stroke. The AFFIRM and RACE studies compared the effects of long term treatment with these two modalities, one primary endpoint being overall morality. The studies found that in these specific populations rhythm control offers no survival advantage over rate control. In addition, the studies revealed that patients have paroxysms of AF that may be undetected. The AFFIRM Investigators. N Engl J Med. 2002;347: ; Van Gelder et al. N Engl J Med. 2002;347: 52

Strokes in Patients Converted to SR
Anticoagulation HRS Education 4/14/2017 9:23 PM n Rate control Rhythm control RR (95% CI) P AFFIRM 4917 5.7% 7.3% 1.28 ( ) .12 RACE 522 5.5% 7.9% 1.44 ( ) .44 STAF 266 1.0% 3.0% 3.01 ( ) .52 PIAF 252 0.8% 1.02 ( ) .49 Total 5957 5.0% 6.5% 1.28 ( ) .08 Take home point: Stroke risk persists even in patients in SR. Verheugt et al. J Am Coll Cardiol. 2003;41(suppl):130A. 53

Proportion Free of Asymptomatic Event
Prevalence of Asymptomatic AF in Drug Trials Patients Studied for 30 Seconds Every 2 Weeks Anticoagulation HRS Education 4/14/2017 9:23 PM 1.0 Azimilide (382) 0.9 0.8 Proportion Free of Asymptomatic Event Placebo (233) Take home point: Recurrent AF episodes can be silent. This may be the etiology of stroke in patients who appear to be in SR. Background: Although most patients with AF are initially identified because they become symptomatic, some patients experience no symptoms when AF is present. Patients commonly experience both symptomatic and asymptomatic AF. Because of the difficulty in documenting asymptomatic events, it is difficult to determine what effect, if any, antiarrhythmic agents have on these events. The efficacy of the antiarrhythmic drug azimilide was studied in 4 double-blind, randomized, placebo-controlled clinical trials. One thousand three hundred eighty patients in SR with a history of symptomatic AF or flutter were enrolled in these studies. Patients were randomized to receive either placebo or azimilide ( mg) once daily for 6 or 9 months. Study patients wore event recorders and transtelephonically transmitted their recordings any time they became symptomatic. Patients also systematically transmitted 30-second recordings every 2 weeks at a time when they were experiencing no symptoms. Patients receiving 100 mg or 125 mg of azimilide were compared with patients receiving placebo to evaluate the occurrence of asymptomatic AF. Asymptomatic AF was seen in 13% of patients taking azimilide compared with 18% of patients taking placebo (P=.09). This study concluded that azimilide may reduce the occurrence of asymptomatic AF, but even with antiarrhythmic therapy, AF is not eliminated. 0.7 100 mg or 125 mg azimilide 0.6 Placebo 0.5 Time (weeks) Page et al. Circulation. 2003;107: 54

Detection of Recurrent AF: ECG vs Implanted Device Recording
Anticoagulation HRS Education 4/14/2017 9:23 PM 100 80 P<.0001 60 Number of Patients Take home point: Recurrent AF episodes can be silent. This may be the etiology of stroke in patients who appear to be in SR. Background: Patients with AF often experience symptoms such as palpitations, dyspnea, dizziness, and syncope. However, there are many AF patients who do not experience any symptoms associated with AF. Documenting the occurrence of such asymptomatic AF has proved to be difficult. In addition, many trials indicate that the long-term effect of undetected recurrent AF on patients remains uncertain. Therefore, a prospective study of 110 patients with a history of paroxysmal or persistent AF was designed to evaluate asymptomatic AF recurrences utilizing an implantable pacemaker capable of monitoring and treating AF. The new design allows for special algorithm detection of AF and is capable of detecting 98% of AF episodes. In addition to the implantation, follow-up included a 12-lead resting ECG and a telemetric ECG to gather simultaneous intracardiac recordings. Patients were also interviewed during each follow-up visit to determine the presence or absence of symptoms. All patients were on antiarrhythmic therapy that was optimized as necessary and maintained constantly throughout the study. Seventy-one percent of patients were orally anticoagulated. The remaining patients did not receive anticoagulation therapy because of contraindication, patient preference, or exhibition of only short paroxysms of AF (less than 1 hour in duration). Mean follow-up was 19 months with 678 follow-up visits, a median of 7 per patient. As shown in this slide, the implantable device detected far more episodes of AF compared with ECG recordings collected during follow-up. AF was documented by resting ECG during follow-up in 46% of patients versus 88% by the implanted device (P<.0001). In 52% of the patients, asymptomatic AF was detected at least once solely by the implanted device. 40 Implanted device 20 ECG Baseline FU1 FU2 FU3 FU4 FU5 FU6 FU7 FU8 FU9 FU10 n=110 110 110 110 85 73 60 48 39 25 15 FU=follow-up. Israel et al. J Am Coll Cardiol. 2004;43:47-52. 55

Prevalence of Recurrent AF During Follow-up
Anticoagulation HRS Education 4/14/2017 9:23 PM Patients (%) 70 60 50 40 30 20 10 AF >72 h AF >48 h AF >24 h AF >12 h AF <12 h Take home point: Recurrent AF episodes can be silent. This may be the etiology of stroke in patients who appear to be in SR. Background: Device implantation also recorded the duration of AF. As outlined in this slide, AF recurrence lasted more than 72 hours in 38% of patients, more than 48 hours in 45% of patients, more than 24 hours in 53% of patients, and more than 12 hours in 64% of patients. AF that lasted less than 12 hours was recorded in 22% of patients. Thus, not only are AF episodes generally undetected, but the length of AF episodes in many patients is longer than 48 hours, which is thought to allow the development of thrombus. Israel et al. J Am Coll Cardiol. 2004;43:47-52. 56

Intracranial Hemorrhage: The Most-Feared Complication of Antithrombotic Therapy
Anticoagulation HRS Education 4/14/2017 9:23 PM >10% of intracerebral hemorrhages (ICH) occur in patients on antithrombotic therapy Aspirin increases the risk of ICH by ~40% Warfarin (INR 2-3) doubles the risk of ICH to 0.3%-0.6% per year ICH during anticoagulation is usually catastrophic Take home point: The flip side of the benefits of anticoagulation are the risks associated with bleeding. While there are algorithms for stroke risk assessment, there are none for the risk of bleeding. Hart et al. Stroke. 2005;36: 57

Absolute Rates of Primary ICH
Anticoagulation HRS Education 4/14/2017 9:23 PM Estimated Absolute Rates of Primary Intracerebral Hemorrhage General population, age ~70 y 0.15%/y Aspirin (any dosage) Atrial fibrillation 0.2%/y Cerebrovascular disease 0.3%/y Aspirin plus clopidogrel 0.4%/y Warfarin (INR 2.5) %/y %/y Warfarin (INR 2.5) plus aspirin %/y Take home point: There are data that give rates of ICH with anticoagulation and antiplatelet agents. EP: Progress Indicator 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objective 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Hart et al. Stroke. 2005;36: 58

CNS Bleeding and Anticoagulation
Anticoagulation HRS Education 4/14/2017 9:23 PM Intracranial Hemorrhage vs Anticoagulation Intensity in AF Patients: 2 Recent Studies Absolute rate Relative risk For library only Case Control Study mean age: cases=78 y; controls 75 y Longitudinal Cohort Study mean age =71 years Take home point: The risk of ICH can be correlated to INR. Reference point EP: Progress Indicator 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objective 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] INR INR Hart et al. Stroke. 2005;36: 59

CNS Bleeding and Anticoagulation
Anticoagulation HRS Education 4/14/2017 9:23 PM Intracranial Hemorrhage vs Anticoagulation Intensity in AF Patients: 2 Recent Studies Longitudinal Cohort Study Case Control Study Absolute Rate Relative Risk Mean age, 71 years Mean age, cases=78 years, controls=75 years INR Rate per 100 Person-Years <1.5 0.5 1.4 0.3 1.2 1.0 (reference) — 0.6 0.4 4.6 2.7 >4.0 8.8 >4.5 9.4 For library only Take home point: The risk of ICH can be correlated to INR. EP: Progress Indicator 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objective 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Hart et al. Stroke. 2005;36: 60

INR at the Time of Stroke or Bleeding Efficacy and Safety of Warfarin
Anticoagulation HRS Education 4/14/2017 9:23 PM 20 15 Ischemic stroke Intracranial bleeding Odds Ratio 10 Take home point: The risk of ischemic and hemorrhagic stroke is related to INR. 5 EP: Progress Indicator 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objective 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] 1 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 Fuster et al. J Am Coll Cardiol. 2006;48: INR 61

ICH During Long-term Anticoagulation With Warfarin Meta-analysis
Anticoagulation HRS Education 4/14/2017 9:23 PM INR INR INR ICH (%/year) INR Take home point: The risk of bleeding is related to INR. Background: Long-term anticoagulation therapy is associated with a risk of ICH. A few of the studies assessed in Levine et al raised concerns regarding bleeding events, such as ICH, in patients on warfarin therapy. For example, the SPAF II study, a sister study to the SPAF III, assessed warfarin effects in AF patients over 75 years of age. The study found increased major bleeding with warfarin versus aspirin (2.3%/year with warfarin vs 1.1% with aspirin) in the group older than 75, and 4.2% per year versus 1.7% per year in patients 75 or younger. In addition, ICH was 1.8% per year with warfarin and 0.6% with aspirin. However, the INR range in this study was 2.0 to 4.5. SPAF II concluded that virtually all ICH was associated with an INR of greater than 3; therefore, the higher bleeding rates are most likely due to high intensity of warfarin therapy. Compared with this, the SPAF III trial had an intensity range of 2 to 3 and bleeding rates were 2.1% per year and 0.4% for ICH in the warfarin group. In a case-control study, an increase of approximately 1 INR was associated with 2 times the risk of ICH. Therefore, the data represented in the slide confirm that the rate of ICH is affected by increasing intensity of warfarin therapy, particularly in patients 75 years or older. INR INR <3.0 INR <3.0 INR Fihn (AF) Fihn (>75) SPAF (AF) SPAF-2 (75) SPAF-2 (75) SPAF-3 (AF) Turpie (PVa) Pengo(PVa) aPV=prosthetic valves. Levine et al. Chest. 2001;119:108S-121S. EP: Progress Indicator 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objective 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] 62

Antithrombotic Therapy for AF ACC/AHA/ESC Guidelines 2006
Anticoagulation HRS Education 4/14/2017 9:23 PM Risk Category Recommended Therapy No risk factors CHADS2 = 0 Aspirin, mg qd One moderate-risk factor CHADS2 = 1 Aspirin, mg/d or warfarin (INR , target 2.5) Any high-risk factor or >1 moderate-risk factor CHADS2 2 or mitral stenosis Warfarin Prosthetic valve (INR , target 3.0) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 63

Class I Recommendations: Preventing Thromboembolism
Anticoagulation HRS Education 4/14/2017 9:23 PM Antithrombotic therapy for all patients with AF, except those with lone AF or contraindications. (Level of Evidence: A) Antithrombotic agent should be based on absolute risk of stroke and bleeding and RR and benefit for patient. (Level of Evidence: A) For patients without mechanical heart valves at high risk of stroke, warfarin is recommended in a dose adjusted to achieve INR of 2.0 to 3.0, unless contraindicated. (Level of Evidence: A) Anticoagulation with a VKA for patients with >1 moderate-risk factor (eg, ≥75 y, HTN, HF, impaired LV systolic function, and DM). (Level of Evidence: A) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 64

Class I Recommendations (cont’d)
Anticoagulation HRS Education 4/14/2017 9:23 PM INR determined at least weekly during initiation of therapy and monthly when anticoagulation is stable. (Level of Evidence: A) Aspirin, mg daily, as an alternative to VKA in low-risk patients or those with contraindications to oral anticoagulation. (Level of Evidence: A) For patients with AF who have mechanical heart valves, target intensity of anticoagulation should be based on type of prosthesis, maintaining an INR of at least 2.5. (Level of Evidence: B) Antithrombotic therapy is recommended for patients with AFl as for those with AF. (Level of Evidence: C) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 65

Class IIa Recommendations: Preventing Thromboembolism
Anticoagulation HRS Education 4/14/2017 9:23 PM For patients with nonvalvular AF and 1 of the following risk factors, treatment with aspirin or a VKA is reasonable, based on risk of bleeding complications, ability to safely sustain adjusted chronic anticoagulation, and patient preferences: age ≥75 y (especially in women), HTN, HF, impaired LV function, or DM. (Level of Evidence: A) For patients with nonvalvular AF with ≥1 of the following risk factors, antithrombotic therapy with aspirin or a VKA is reasonable: age 65 to 74 y, female gender, or CAD. Agent choice should be based upon the risk of bleeding complications, ability to safely sustain adjusted chronic anticoagulation, and patient preferences. (Level of Evidence: B) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 66

Class IIa Recommendations (cont’d)
Anticoagulation HRS Education 4/14/2017 9:23 PM Select antithrombotic therapy using the same criteria irrespective of the pattern (ie, paroxysmal, persistent, or permanent) of AF. (Level of Evidence: B) In patients with AF w/o mechanical prosthetic heart valves, it is reasonable to interrupt anticoagulation for up to 1 wk without substituting heparin for surgical or diagnostic procedures that carry a risk of bleeding. (Level of Evidence: C) It is reasonable to re-evaluate the need for anticoagulation at regular intervals. (Level of Evidence: C) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 67

Class IIb Recommendations: Preventing Thromboembolism
Anticoagulation HRS Education 4/14/2017 9:23 PM In patients ≥75 y at risk of bleeding but w/o contraindications to oral anticoagulant therapy, and patients with moderate-risk factors who can’t tolerate anticoagulation at INR 2.0 to 3.0, an INR of 2.0 (range 1.6 to 2.5) may be considered for primary prevention of ischemic stroke and systemic embolism. (Level of Evidence: C) When surgical procedures interrupt oral anticoagulant therapy for longer than 1 wk in high-risk patients, unfractionated heparin (UH) may be administered or low-molecular-weight heparin (LMWH) given by SC injection. (Level of Evidence: C) Following PCI or revascularization in patients with AF, low-dose aspirin (less than 100 mg daily) and/or clopidogrel (75 mg daily) may be given concurrently with anticoagulation to prevent myocardial ischemic events. (Level of Evidence: C) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 68

Class IIb Recommendations (cont’d)
Anticoagulation HRS Education 4/14/2017 9:23 PM During PCI, anticoagulation may be interrupted, but VKA should be resumed soon after PCI and the dose adjusted to an INR in the therapeutic range. Aspirin may be given temporarily, but maintenance should consist of combination of clopidogrel, 75 mg daily, plus warfarin (INR 2.0 to 3.0). Clopidogrel should be given for ≥1 mo after implantation of a bare metal stent, ≥3 mo for a sirolimus-eluting stent, ≥6 mo for a paclitaxel-eluting stent, and ≥12 mo in selected patients, after which warfarin may be given as monotherapy in the absence of a subsequent coronary event. (Level of Evidence: C) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 69

Class IIb Recommendations (cont’d)
Anticoagulation HRS Education 4/14/2017 9:23 PM In patients with AF younger than 60 y without heart disease or risk factors for thromboembolism (lone AF), the risk of thromboembolism is low without treatment and the effectiveness of aspirin for primary prevention of stroke relative to the risk of bleeding has not been established. (Level of Evidence: C) In patients with AF who sustain ischemic stroke or systemic embolism during treatment with low-intensity anticoagulation (INR 2.0 to 3.0), rather than add an antiplatelet agent, it may be reasonable to raise the intensity of anticoagulation to a maximum target INR of 3.0 to (Level of Evidence: C) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 70

Class III Recommendations Preventing Thromboembolism
Anticoagulation HRS Education 4/14/2017 9:23 PM Long-term anticoagulation with a VKA is not recommended for primary prevention of stroke in patients <60 y w/o heart disease (lone AF) or any risk factors for thromboembolism. (Level of Evidence: C) Take home point: This represents the recommendations of the ACC/AHA/ESC guidelines for anticoagulation based on risk. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] Fuster et al. J Am Coll Cardiol. 2006;48: 71

Patient Selection for Anticoagulation: Additional Considerations
Anticoagulation HRS Education 4/14/2017 9:23 PM Risk of bleeding Newly anticoagulated vs established therapy Availability of high-quality anticoagulation management program Patient preferences Take home point: There are several considerations along with stroke risk for the decision to anticoagulate. EP: Progress Indicator 3. Employ CHADS2 results in making management decisions for patients with nonvalvular atrial fibrillation. (performance) 4.Balance CHADS2 risk with risk of bleeding during anticoagulation, patient preferences and the availability of INR monitoring facilities. (knowledge) Learning Objective 2. Employ CHADS2 results when making management decisions to avoid both over- and under-treatment of patients with nonvalvular AF [Progress Indicator 3] 3. Determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities [Progress Indicator 4] Instructional Objectives 3. Given pertinent patient information, participants will be able to employ CHADS2 results to make management decisions to avoid both over- and under-treatment of patients with nonvalvular AF. 4. Given pertinent patient and resource availability information, participants will be able to determine optimal anticoagulation management for patients with nonvalvular AF by appropriate consideration of CHADS2 risk score, risk of bleeding, patient preference, and availability of INR monitoring facilities. CARD: Progress Indicator PCP: 2. Calculate a CHADS2 risk score for a patient with nonvalvular AF and describe the usefulness of the score in making appropriate anticoagulation management decisions [Progress Indicators 2,3] 3. Discuss the importance of balancing CHADS2 risk, risk of bleeding, patient preference, and availability of INR monitoring facilities when making anticoagulation management decisions for patients with nonvalvular AF [Progress Indicator 4] 72

CMS Physician Quality Reporting Initiative
Anticoagulation HRS Education 4/14/2017 9:23 PM Measure #33 – Stroke and stroke rehabilitation: anticoagulant therapy at discharge for AF Percent of patients ≥18 years with ischemic stroke/TIA and permanent, persistent, or paroxysmal AF given A/C at D/C: Report for patients with ischemic stroke/TIA with documented AF at discharge Patients given anticoagulant at D/C All patients ≥18 years with ischemic stroke or TIA and permanent, persistent, or paroxysmal AF Take home point: CMS is evaluating the use of anticoagulation as a quality measure. US Department of Health and Human Services. PQRIMeasuresList.pdf. Accessed on November 14, 2007. 73

CMS Physician Quality Reporting Initiative
Anticoagulation HRS Education 4/14/2017 9:23 PM Clinical recommendation statements Antithrombotic therapy (oral A/C or ASA) to all patients with AF, except lone AF (ACC/AHA/ESC, 2001) (Class I, Level of Evidence: A) Long-term oral A/C (target INR 2.5; range ) in AF patients with recent stroke/TIA (Albers, ACCP, 2001) (Grade 1A) Oral A/C also beneficial in patients with several other high-risk factors Oral A/C (target INR, 2.5; range ) for patients with ischemic stroke/TIA with permanent, persistent, or paroxysmal AF (Sacco, ASA, 2006) (Class I, Level of Evidence: A) Take home point: CMS is evaluating the use of anticoagulation as a quality measure. US Department of Health and Human Services. PQRIMeasuresList.pdf. Accessed on November 14, 2007. 74

Anticoagulation – Full Curriculum

Similar presentations

Presentation on theme: "Anticoagulation – Full Curriculum"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Anticoagulation – Full Curriculum

Similar presentations

Presentation on theme: "Anticoagulation – Full Curriculum"— Presentation transcript:

Similar presentations

About project

Feedback