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The practice recommendations in this presentation are from: European Society of Cardiology

The practice recommendations in this presentation are from: European Society of Cardiology Source: Guidelines for the Management of Atrial Fibrillation. European Heart Journal 2010;31:2369‑429.

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The practice recommendations in this presentation are from: European Society of Cardiology

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  1. The practice recommendations in this presentation are from: European Society of Cardiology Source: Guidelines for the Management of Atrial Fibrillation. European Heart Journal 2010;31:2369‑429. Website: http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-afib-FT.pdf Strength of Evidence:The strength of evidence is indicated following each recommendation. Evidence-based Recommendations

  2. American College of Cardiology, American Heart Association Task Force on Practice Guidelines and European Society of Cardiology Committee for Practice Guidelines Source: ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation. Circulation 2006;114:e257-e354. Website: http://circ.ahajournals.org/cgi/content/full/114/7/e257 Strength of Evidence:The strength of evidence is indicated following each recommendation. Evidence-based Recommendations

  3. American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines Source: 2011 ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial Fibrillation (Updating the 2006 Guideline). Circulation 2011;123:104-23. Website: http://circ.ahajournals.org/cgi/content/short/123/1/104 Strength of Evidence:The strength of evidence is indicated following each recommendation. Evidence-based Recommendations

  4. American College of Cardiology Foundation, American Heart Association Task Force on Practice Guidelines Source: 2011 ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial Fibrillation (Update on Dabigatran). J Am Coll Cardiol 2011;57:1330-7. Website: http://content.onlinejacc.org/cgi/content/full/j.jacc.2011.01.010 Strength of Evidence:The strength of evidence is indicated following each recommendation. Evidence-based Recommendations

  5. American College of Chest Physicians Source: Antithrombotic Therapy in Atrial Fibrillation. Chest 2008;133(Suppl 6):546S-92S. Website: http://chestjournal.chestpubs.org/content/133/6_suppl/546S.full Strength of Evidence:The strength of evidence is indicated following each recommendation. Evidence-based Recommendations

  6. American College of Chest Physicians Source: Pharmacology and Management of the Vitamin K Antagonists. Chest 2008;133(Suppl 6):160S-98S. Website: http://chestjournal.chestpubs.org/content/133/6_suppl/160S.full Strength of Evidence:The strength of evidence is indicated following each recommendation. Evidence-based Recommendations

  7. Overview of Thromboprophylaxis in Atrial Fibrillation Module 1

  8. Module 1: Agenda Epidemiology Nomenclature Evaluation Management issues Atrial fibrillation and stroke Risk assessment

  9. Atrial Fibrillation • Common arrhythmia seen in primary care • Prevalence increases with age • 0.1% in those under 55 years of age • 9.0% in those over 80 years of age • Adverse consequences • Decreased cardiac output • Thrombus formation • Systemic embolization Go AS, et al. JAMA 2001;285:2370-5.

  10. Prevalence of Atrial Fibrillation by Age and Sex 11.1 12 10 8 6 4 2 0 10.3 Error bars represent 95% confidence intervals. 9.1 7.3 7.2 Prevalence (%) 5.0 5.0 3.4 3.0 1.7 1.7 1.0 0.9 Women Men 0.4 0.2 0.1 <55 55-59 60-64 65-69 70-74 75-79 80-84 >85 Age (years) Reprinted with permission from Go AS, et al. JAMA 2001;285:2370-5. .

  11. Projected Number of Adults with Atrial Fibrillation in the United States, 1995-2050 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 Upper and lower curves represent the upper and lower scenarios based on sensitivity analyses. 5.61 5.42 5.16 4.78 4.34 3.80 3.33 Adults with Atrial Fibrillation (millions) 2.94 2.66 2.44 2.26 2.08 1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050 Years Reprinted with permission fromGo AS, et al. JAMA 2001;285:2370-5. .

  12. Projected Age and Sex Distribution of Atrial Fibrillation, 2000-2050 Year 2025 2055 2000 Women 48.6 46.3 47.4 Age group (years) <65 18.0 15.5 11.5 65-79 45.3 48.7 35.9 ≥80 36.7 35.8 52.6 Data presented as percentages. Reprinted with permission fromGo AS, et al. JAMA 2001;285:2370-5.

  13. Nomenclature • Paroxysmal • Persistent • Permanent • Recurrent • Lone (nonvalvular)

  14. Atrial Fibrillation Evaluation • Electrocardiography • Echocardiography • Chest radiography • Thyroid function • Additional testing

  15. Management Issues • Thromboprophylaxis • Cardioversion • Hospitalization • Rate versus rhythm control

  16. AFFIRM: Rate vs. Rhythm Control 30 25 20 15 10 5 0 P=0.08 Cumulative mortality from any cause in the rhythm-control group and the rate-control group. Rhythm Control Cumulative Mortality (%) Rate Control 0 1 2 3 4 5 Years AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management. Reprinted with permission from Wyse DG, et al. N Engl J Med 2002;347:1825-33.

  17. In patients with AF and CHF, a routine strategy of rhythm control did not reduce the rate of death from CV causes, compared with a rate-control strategy. Conclusion from AFFIRM Trial AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management. Wyse DG, et al. N Engl J Med 2002;347:1825-33.

  18. Why Thromboprophylaxis? • Every 40 seconds, an American has a stroke. • Atrial fibrillation is a powerful risk factor for stroke: • Increases risk fivefold throughout all ages • Percentage of strokes attributable to AF increases steeply with age, from 1.5% (50-59 years of age) to 23.5% (80-89 years of age) Heart disease and stroke statistics-2010 update. Circulation 2010;121:e46-e215.

  19. CHADS2 Scoring CHF = congestive heart failure; TIA = transient ischemic attack. Information from Gage BF, et al. JAMA 2001;285:2864-70.

  20. CHADS2 and Adjusted Stroke Rate Information from Gage BF, et al. JAMA 2001;285:2864-70.

  21. Module 1: Summary Points Atrial fibrillation is common and prevalence increases with age. Management has shifted from rhythm control to rate control. Stroke can be a common, serious sequelae of atrial fibrillation. CHADS2 can estimate stroke risk in patients with atrial fibrillation.

  22. Recommendation #1: The CHADS2 score is recommended as a simple initial means of assessing stroke risk in nonvalvular atrial fibrillation. (I A) Evidence-based Recommendation ESC. European Heart Journal 2010;31:2369‑429.

  23. Recommendation #2: Antithrombotic therapy to prevent thromboembolism is recommended for all patients with atrial fibrillation (AF), except those with lone AF or contraindications. (I A) Evidence-based Recommendation ACC/AHA/ESC. Circulation 2006;114:e257-354.

  24. Choice of Thromboprophylaxis Agent Module 2

  25. Module 2: Agenda Efficacy data for aspirin and vitamin K antagonists Dual antiplatelet therapy versus warfarin Dual antiplatelet therapy plus warfarin

  26. Aspirin Aspirin modestly effective at preventing stroke 20% stroke reduction compared with placebo Aspirin Compared with Placebo Relative Risk Reduction (95% CI) AFASAK I SPAF EAFT ESPS II LASAF UK-TIA All Trials -100% 100% -50% 0% 50% Aspirin Better Aspirin Worse CI = confidence interval. Reprinted with permission from Hart RG, et al. Ann Intern Med 1999;131:492-501.

  27. Vitamin K Antagonists Vitamin K antagonists more effective at preventing stroke ~60% stroke reduction compared with placebo Adjusted-Dose Warfarin Compared with Placebo Relative Risk Reduction (95% CI) AFASAK I SPAF BAATAF CAFA SPINAF EAFT All Trials 0% 50% -50% -100% 100% Warfarin Better Warfarin Worse CI = confidence interval. Reprinted with permission from Hart RG, et al. Ann Intern Med 1999;131:492-501.

  28. Vitamin K Antagonists vs. Aspirin Vitamin K antagonists more effective than aspirin at preventing stroke ~30% stroke reduction compared with aspirin Warfarin Compared with Aspirin Relative Risk Reduction (95% CI) AFASAK I AFASAK II EAFT PATAF SPAFII All Trials 0% -50% -100% 100% 50% Warfarin Better Warfarin Worse CI = confidence interval. Reprinted with permission from Hart RG, et al. Ann Intern Med 1999;131:492-501.

  29. Aspirin: Role in Therapy Relatively low risk for stroke Anticoagulant therapy contraindicated

  30. Aspirin: Role in Therapy Aspirin or no therapy is acceptable for patients less than 60 years of age with no heart disease (lone AF). Singer DE, et al. Chest 2008;133(suppl 6): 546S-92S.

  31. Clopidogrel for Thromboprophylaxis ACTIVE A Aspirin and clopidogrel more effective at preventing adverse events compared with aspirin alone ACTIVE W Warfarin more effective at preventing adverse events compared with aspirin plus clopidogrel Warfarin remains standard of care. However, dual antiplatelet may be useful in some patients unable to use anticoagulation. Connolly SJ, et al. Lancet 2006;367:1903-12. Connolly SJ, et al. N Engl J Med 2009;360:2066-78.

  32. Aspirin, Clopidogrel and Warfarin Might be indicated in patients with atrial fibrillation and mechanical valve and/or a drug-eluting stent Increased risk of bleeding with this strategy No prospective trial data Holmes DR, et al. J Am Coll Cardiol 2009;54:95-109.

  33. Module 2: Summary Points Warfarin is mainstay of therapy for stroke prophylaxis in patients with atrial fibrillation. Aspirin is appropriate for patients who are at low risk of stroke and have nonvalvular disease. Aspirin plus clopidogrel may be an option for patients who are not candidates for anticoagulation if they have no prior history of stroke or transient ischemic attack.

  34. Recommendation #3:The selection of antithrombotic agents should be based on the absolute risk of stroke and bleeding, and the relative risk and benefit for a given patient. (I A) Recommendation #4: Aspirin, 81 mg-325 mg daily, is recommended as an alternative to vitamin K antagonists in low-risk patients or in those with contraindications to oral anticoagulation. (I A) Evidence-based Recommendations ACC/AHA/ESC. Circulation 2006;114:e257-354.

  35. Recommendation #5:The addition of clopidogrel to aspirin to reduce the risk of major vascular events, including stroke, might be considered in patients with atrial fibrillation in whom oral anticoagulation with warfarin is considered unsuitable due to patient preference or physician assessment of the patient’s ability to safely sustain anticoagulation. (IIb B) Evidence-based Recommendation ACCF/AHA/HRS. Circulation 2011;123:104-23.

  36. Recommendation #6:For patients with a CHADS2 score ≥2, chronic oral anticoagulant therapy with a vitamin K antagonist is recommended in a dose-adjusted regimen to achieve an INR range of 2.0-3.0 (target: 2.5), unless contraindicated. (I A) Evidence-based Recommendation ESC. European Heart Journal 2010;31:2369‑429.

  37. Warfarin: Issues and Controversies Module 3

  38. Module 3: Agenda Warfarin overview Physician confidence with warfarin Strategies to improve patient adherence Challenging situations Surgery Dental procedures Risk of gastrointestinal bleeding Use in the elderly

  39. Warfarin: Overview • Decreases vitamin K dependent clotting factors • I, VII, IX, X and protein C and S • Oral absorption: peak levels at 4 hours • Metabolism: CYP2C9 hepatic enzyme system • Half-life: 36 to 42 hours

  40. Warfarin: Starting Dose • Ultimate anticoagulant effect delayed until normal clotting factors (especially prothrombin) are cleared from the circulation • Prothrombin half-life: 3 days • Studies show 5 mg is preferred starting dose over 10 mg • 2008 ACCP guidelines recommend 5 mg/day-10 mg/day starting dose Harrison L, et al. Ann Intern Med 1997;126:133-6. Singer DE, et al. Chest 2008;133(Suppl 6):546S-92S.

  41. Starting Warfarin: Issues • Role of hospitalization • Bridging with heparin

  42. Warfarin: Dosing and Monitoring • INR target is 2.5 (range: 2.0-3.0) for atrial fibrillation • Dosing algorithms exist • Monitoring software exists • webINR • Pharma-File • WarfarinDosing.org • CoaguChek (self-monitoring) Dosing algorithm available in downloadable resources

  43. Warfarin Monitoring • Relative efficacy of management strategies (time in range) • Self-management 72% • Randomized trials 66% • Anticoagulation clinics 66% • Community physicians 57% Cromheecke ME, et al. Lancet 2000;356:97-102.

  44. Importance of Strict INR Control INR Level by Event Type and History of Stroke 8 7 6 5 4 3 2 1 Odds Ratios TE – no history of stroke TE – history of stroke ICH – no history of stroke ICH – history of stroke < 1.5 1.5-1.9 2.0-2.5 (referent) 2.6-3.0 3.1-3.5 >=3.6 INR TE= thromboembolism; ICH= intracranial hemorrhage. Reprinted with permission from Singer DE, et al. Circulation 2008;118:S_757.

  45. Warfarin: Adverse Events • Anticoagulants are among top drugs associated with safety incidents in the U.S. • Warfarin is one of the anticoagulants most often cited in medication error reports • Risk of major bleeding roughly 1% a year • Risk of minor bleeding roughly 10% a year • Risks are higher in certain settings Joint Commission Sentinel Event Alert, Issue 41, 2008. Prasad S, et al. J Fam Pract. 2009;58(7):346-52.

  46. Influence of Diet on Warfarin • The currently recommended daily allowance of vitamin K is 65 mcg/day-80 mcg/day • Changes to diet can increase or decrease INR • A diet high in vitamin K can be overcome with higher warfarin dose • Foods high in vitamin K include kale, spinach, collard greens Link to patient education handout available in downloadable resources

  47. Common Drugs that Interact with Warfarin Link to patient education handout available in downloadable resources

  48. Warfarin: An Underused Therapy Studies show: • Warfarin taken by only 30%-60% of appropriate patients • Problem particularly pronounced in the elderly and women Lip GY, et al. Br J Clin Pharmacol 2007;64(5):575-7.

  49. Warfarin: Improving Adherence • Improve patient understanding • Educate about effects of lifestyle factors (e.g., diet, smoking, drinking) on warfarin metabolism and INR • Educate patients about home monitoring • Research shows this improves the quality of anticoagulation management1 • Avoid complicated dosing schedules • Greater communication between doctor and patient 1Cromheecke ME, et al. Lancet 2000;356:97-102

  50. Warfarin and Surgery • LearningLink survey: 75% of participants said they find it challenging to manage atrial fibrillation patients who are about to undergo surgery

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