1 / 54

Anticoagulation in Atrial Fibrillation

Anticoagulation in Atrial Fibrillation. Roger Kerzner , MD Christiana Care Cardiology Consultants March 28 th , 2014. Disclosures. None. Objectives. Atrial fibrillation basics, and why we use anticoagulation Who should be anticoagulated

xenon
Download Presentation

Anticoagulation in Atrial Fibrillation

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Anticoagulation in Atrial Fibrillation Roger Kerzner, MD Christiana Care Cardiology Consultants March 28th, 2014

  2. Disclosures • None

  3. Objectives • Atrial fibrillation basics, and why we use anticoagulation • Who should be anticoagulated • Risk calculators and how to apply to clinical decision making • How to address fall risk • Agents available for anticoagulation • When and when not to hold anticoagulation for procedures

  4. Anticoagulation in Atrial Fibrillation Atrial fibrillation basics

  5. Atrial Fibrillation Basics: Definitions • Paroxysmal • Spontaneous termination within 7 days • Persistent • Episodes lasting longer than 7 days • Generally require cardioversion to restore sinus rhythm • Permanent or Chronic

  6. Atrial Fibrillation Basics: Epidemiology • 2.2 million Americans have atrial fibrillation. • Median age is 75 years • Lifetime risk of developing atrial fibrillation is 1:6, and increases to 1:4 in men and women older than 40 years • The mortality rate of patients with atrial fibrillation is about double thatof patients in normal rhythm, and linked to the severityof underlying heart disease. J Am CollCardiol, 2011; 57:101-198

  7. Atrial Fibrillation Basics: Morbidity • Common symptoms include palpitations,chest pain, dyspnea, fatigue, lightheadedness, or syncope. • In many patients, particularly the elderly, atrial fibrillation is asymptomatic. • It is the most common arrhythmia in clinical practice, accountingfor approximately one-third of hospitalizations for cardiacrhythm disturbances J Am CollCardiol, 2011; 57:101-198

  8. Atrial Fibrillation Basics: Morbidity : Stroke • The rate of ischemic stroke among patients with atrial fibrillation averages 5% per year, which is 2 to 7 times that of people without atrial fibrillation. • One of every 6 strokes occursin a patient with atrial fibrillation. • Strokes in patients with atrial fibrillation tend to be more debilitating. J Am Coll Cardiol, 2011; 57:101-198

  9. Atrial Fibrillation Basics: Morbidity : Stroke • The risk of stroke is present regardless of the type, duration, or symptoms related to atrial fibrillation. • In the AFFIRM trial, there we more strokes in the arm of the trial in which patients were thought to be in sinus rhythm, and their anticoagulation was stopped. J Am Coll Cardiol, 2011; 57:101-198, N Engl J Med. 2002 Dec 5;347(23):1825-33.

  10. Anticoagulation in Atrial Fibrillation Why we use anticoagulation

  11. Anticoagulation: Randomized Trials • Approximately 20,000 patients enrolled in trials of warfarin versus placebo. • Target INR approximately 2.0-3.0 • Often >90% of patients with AF excluded from trials • Mean follow-up 1.6 years • Average age of 69 years • Average age of AF patients in clinical practice is 75 years • Meticulous monitoring of INRs Hart RG, et al. Ann Intern Med 1999;131:492-501 Fuster V, et al. J Am Coll Cardiol 2006;48:854-906 Birman-Deych E, et al. Stroke 2006;37:1070-4

  12. Randomized Trials : Warfarin vs. Placebo for prevention of stroke 62% reduction in risk of stroke 2.7% absolute reduction per year for primary prevention 8.4% absolute reduction per year for secondary prevention 26% reduction in all cause mortality Hart RG, et al. Ann Intern Med 1999;131:492-501

  13. Randomized Trials : Aspirin ~20% reduction in risk of stroke Hart RG, et al. Ann Intern Med 1999;131:492-501 Eur Heart J 2007; 28; 926-8

  14. Anticoagulation: Failed Strategies • Plavix and Aspirin vs. Warfarin • Randomized Trial (n=6706) [ACTIVE Trial. Lancet 2006;367:1903-12] • Low-intensity Warfarin (INR 1.2-1.5) vs. Aspirin • Randomized Trial (n=1044) [SPAF III. Lancet 1996;348:633-8] • Rhythm Control • Eliminate the atrial fibrillation with antiarrhythmic medications • Randomized Trial (n=4060) [AFFIRM. NEJM 2002:347:1825-33]

  15. Anticoagulation in Atrial Fibrillation Who should be anticoagulated

  16. Who should be anticoagulated? • Patients with valvular heart disease. • Valvular atrial fibrillation = Patients with atrial fibrillation and rheumatic mitral valve disease, a prosthetic heart valve, or valve repair. • The risk of stroke in patients with rheumatic mitral valve disease is very high. J Am Coll Cardiol, 2011; 57:101-198

  17. Who should be anticoagulated? • Patients with non-valvular heart disease, and risk factors for stroke in atrial fibrillation. • Basically all patients with atrial fibrillation, but without rheumatic heart disease • Patients with lone atrial fibrillation should not be anticoagulated. • Lone atrial fibrillation = individuals younger than 60 years, without clinical or echocardiographic evidence of cardiopulmonary disease, including hypertension, or other risk factors for stroke J Am Coll Cardiol, 2011; 57:101-198

  18. Anticoagulation in Atrial Fibrillation Risk calculators and how to apply to clinical decision making

  19. The Problem with Anticoagulation = Bleeding • Risk of intracerebral hemmorhage is between 0.1-0.6% Oden A, et al. Thromb Res 2006;117:493-9 Fuster V, et al. J Am Coll Cardiol 2006;48:854-906

  20. The Problem with Anticoagulation = Bleeding • The answer to the problem of bleeding risk = risk calculators. • Use calculators of stroke and bleeding risk to determine the risk/benefit ratio of starting a patient on a strong blood thinner. • For each calculator, one adds up the number of points a patient has, and this correlates with the risk of a stroke or bleeding event.

  21. Estimating the Risk of StrokeCHADS2 Score Score CHADS2 Risk Criteria Gage BF, et al. JAMA 2001;285:2864-70

  22. Estimating the Risk of StrokeCHADS2 Score % Adjusted Stroke Risk/Year CHADS2 Score Gage BF, et al. JAMA 2001;285:2864-70

  23. Estimating the Risk of StrokeCHA2DS2-VASc Score Score CHA2DS2-VASc Risk Criteria Gage BF, et al. JAMA 2001;285:2864-70

  24. Estimating the Risk of StrokeCHA2DS2-VASc Score CHA2DS2-VASc Score % Adjusted Stroke Risk/Year EurHeart J 2010; 31:2369

  25. Estimating the Risk of Stroke • Examples • 80 year old male with a history of heart failure with an ejection fraction of 40%, hypertension, and a prior stroke • CHADS2 Score = 5 -> stroke risk 12.5%/year • 70 year old female with a prior myocardial infarction • CHA2DS2-VASc Score = 3 -> stroke risk 3.2%/year

  26. CHA2DS2-VASc Score or CHADS2 Score Recommended Therapy • 0 • 1 • 2 or more • Aspirin, 81 to 325 mg daily • Aspirin or Anticoagulation • Anticoagulation Modified 2011 Guidelines Approach CHA2DS2-VASc score is preferred as it has better discrimination of risk at a low CHADS2 score. J Am Coll Cardiol, 2011; 57:101-198

  27. Estimating the Risk of BleedingHAS-BLED Score Score HAS-BLED Risk Criteria Chest. 2010 Nov;138(5):1093-100

  28. Estimating the Risk of BleedingHAS-BLED Score HAS-BLED Score % Major Bleeding Risk/Year EurHeary J 2012; 33; 1500-10

  29. Balancing the Risk of Stroke and Bleeding • Example • 80 year old male with a history of heart failure with an ejection fraction of 40%, hypertension, a prior stroke, and chronic kidney disease • CHADS2 Score = 5 -> stroke risk 12.5%/year • HAS-BLED Score = 4 -> major bleeding risk 3.4%/year

  30. Anticoagulation in Atrial Fibrillation How to address fall risk

  31. How to address fall risk • Analysis of 1245 Medicare patients with AF at high risk for falls • Data accumulated as part of a quality improvement initiative. • Risk of intracranial hemmorhage in patients at high risk for falls = 2.8 per 100 patient-years • Risk of stroke in falls vs. non-falls patients = 13.7 vs. 6.9 per 100 patient-years • Despite a high risk for falls, patients with 2 or more risk factors for stroke benefit from anticoagulation therapy Gage BF, et al. Am J Med 2005;118:612-7

  32. Anticoagulation in Atrial Fibrillation Agents available for anticoagulation

  33. Warfarin • Vitamin K antagonist, which prevents the creation of Vitamin K dependent elements of the coagulation cascade. • Adjusted to a trial-proven level of anticoagulation. • INR = 2.0-3.0

  34. Limitations of Warfarin Limitation Slow onset of action Genetic variation in metabolism Multiple food and drug interactions Narrow theraputic range Consequence Overlap with parenteral anticoagulation Variable dose requirements Frequent coagulation monitoring Frequent coagulation monitoring JI Weitz Presentation, Boston Atrial Fibrillation Symposium, Boston, MA, Jan 14 2011.

  35. Limitations of Warfarin • Risk of intracerebralhemmorhage is between 0.1-0.6% • Close monitoring of INRs is critical Oden A, et al. Thromb Res 2006;117:493-9 Fuster V, et al. J Am Coll Cardiol 2006;48:854-906

  36. Warfarin Monitoring • Warfarin monitoring and dose adjust should be coordinated through an anticoagulation management service (anticoagulation clinic) • On average, patients followed in community physician practices are in the theraputic range only 57% of the time, and this increases by approximately 8% in anticoagulation clinic. • Christiana cardiology practice clinic = TTR ~ 72% CHEST 2008; 133:160S–198S, Chest. 2006 May;129(5):1155-66

  37. Anticoagulation in Atrial Fibrillation The Novel anticoagulants (NOACs)

  38. Mechanisms of New Agents Rivaroxiban Apixaban Edoxaban Warfarin Dabigatran http://commons.wikimedia.org/wiki/File:Coagulation_simple.svg

  39. Comparison of warfarin vs newer agents JI Weitz Presentation, Boston Atrial Fibrillation Symposium, Boston, MA, Jan 14 2011.

  40. Dabigatran : RELY Trial • A noninferiority trial of 18,113 patients with atrial fibrillation randomized to: • In a blinded fashion, fixed doses of dabigatran 110 mg or 150 mg twice daily or • In an unblinded fashion, adjusted-dose warfarin • Mean age 71 years; 64% male; Mean CHADS2 score of 2.1. • The median follow-up was 2 years. • The primary outcome was stroke or systemic embolism. Connolly SJ et al. N Engl J Med 2009;361:1139-1151.

  41. Dabigatran : RELY Trial : Stroke 110mg dose noninferior, & 150mg dose superior to warfarin for reduction in stroke or systemic embolism. Benefit present regardless of age, CHADS2 score, renal function, or time with INRs in theraputic range. Schirmer, S. H. et al. J Am Coll Cardiol 2010;56:2067-2076

  42. Dabigatran : RELY Trial : Bleeding Reduction in total bleeding with both doses compared to warfarin In the elderly, lower risk of stroke and intracranial bleeding, But higher risk of extracranial (mostly GI) bleeding. JI Weitz Presentation, Boston Atrial Fibrillation Symposium, Boston, MA, Jan 14 2011. Schirmer, S. H. et al. J Am Coll Cardiol 2010;56:2067-2076

  43. Apixaban: AVERROES Trial • A double blind, controlled trial of 5599 patients with atrial fibrillation, but not candidates for warfarin, randomized to: • Afixed dose of apixaban 5mg twice daily or aspirin (81-324mg) daily • Mean age 71 years; 58% male; Mean CHADS2 score of 2.1. • The mean follow-up was only 1.1 years, as the trial was stopped earlier. • The primary outcome was stroke or systemic embolism. Connolly SJ et al. N Engl J Med 2011;364:806-817

  44. Apixaban: AVERROES Trial: Stroke Apixaban was superior to aspirin with over a 50% reduction ofstroke or systemic embolism. Benefit present regardless of age, CHADS2 score, renal function, or prior use of warfarin. Connolly SJ et al. N Engl J Med 2011;364:806-817

  45. Apixaban: AVERROES Trial: Bleeding No statistically significant increase in the risk of major bleeding or intracranial bleeding. Connolly SJ et al. N Engl J Med 2011;364:806-817

  46. Novel Anticoagulants • Equivalent, or superior efficacy to warfarin for the reduction of stroke or systemic embolism. • Superior safety compared to warfarin for the reduction of serious bleeding. • Apixaban is superior to aspirin for the reduction of stroke and systemic embolism, with a similar risk of bleeding. • None of the NOACs have been directly compared, thus it is difficult to determine which agent is the best agent. N Engl J Med. 2009 Sep 17;361(12):1139-51, Connolly SJ et al. N Engl J Med 2011;364:806-817, N Engl J Med. 2011 Sep 8;365(10):883-91, N Engl J Med. 2011 Sep 15;365(11):981-92

  47. Novel Anticoagulants : Unique Traits • Dabigatran (Pradaxa) • Twice daily *Renal dose not included in RCT • Superior to warfarin for stroke reduction • Rivaroxiban (Xarelto) • Once daily *Renal included in RCT • Equivalent to warfarin for stroke reduction • Higher CHADS score compared to other RCTs • Apixaban (Eliquis) • Twice daily*Renal included in RCT • Superior to warfarin for stroke and mortality reduction • Only agent demonstrated superior to aspirin N Engl J Med. 2009 Sep 17;361(12):1139-51, Connolly SJ et al. N Engl J Med 2011;364:806-817, N Engl J Med. 2011 Sep 8;365(10):883-91, N Engl J Med. 2011 Sep 15;365(11):981-92

  48. Practical points for using NOACs • Only approved for non-valvular atrial fibrillation • Start NOACs when INR < 2.0 • Contraindicated in patients with severe renal insufficiency (CrCl < 15) • Except apixaban • Normal aPTT indicates absent activity • Potential cost issues

  49. Practical points for using NOACs • Dabigatran (Pradaxa) • Twice daily • 150mg BID, or 75mg BID if CrCl 15-30 • Dyspepsia in 10% of pateints • Rivaroxiban (Xarelto) • Once daily, with largest meal of the day • 20mg daily, or 15mg daily if CrCl 15-50 • Apixaban (Eliquis) • Twice daily • 5mg BID, or 2.5mg BID if at 2 of these items present (>80 yo, <60 kg, Cr > 1.5)

  50. Anticoagulation in Atrial Fibrillation When and when not to hold anticoagulation for procedures

More Related