Atrial Fibrillation Anticoagulation

Aka: Atrial Fibrillation Anticoagulation, Anticoagulation in Atrial Fibrillation, Atrial Flutter Anticoagulation

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II. Indications: Longterm Anticoagulation in Atrial Fibrillation

  1. CVA Prevention in Atrial Fibrillation
    1. Start immediately after Transient Ischemic Attack
    2. Initiation timing after Cerebrovascular Accident dependent on CVA characteristics (consult stroke neurology)
  2. CHADS Score (or CHADS2-VASc Score) of 2 or higher (consider for 1 or higher)
    1. Consider Outpatient Bleeding Risk Index or HAS-BLED Score or DOAC Score
    2. Consider Left Atrial Appendage Closure Device (e.g. Watchman Device) as alternative
  3. Preparation for Atrial Fibrillation Cardioversion
    1. Atrial Fibrillation longer than 48 hours
    2. Cardioversion without Anticoagulation risks embolism
  4. Following cardioversion for 3 weeks
    1. Increased risk of Thromboembolism after electrical cardioversion (stunned Myocardium)

III. Indications: Longterm Anticoagulation in Atrial Fibrillation by specific risk factors

  1. Indications: High Risk
    1. Prior Cerebrovascular Accident or Thromboembolism
    2. Rheumatic mitral valve disease or Mitral Stenosis
    3. Prosthetic Heart Valve
  2. Indications: Moderate Risk (could consider Aspirin)
    1. Hypertension
    2. Left Ventricular Failure
    3. Cardiomyopathy
    4. Age over 75 years old
    5. Diabetes Mellitus
  3. Indications: Less Validated Factors
    1. Coronary Artery Disease with preserved LV function
    2. Age 65 to 75 years old (especially women)
    3. Hyperthyroidism

IV. Management: Short-term Anticoagulation prior to Cardioversion

  1. Protocol
    1. Assumes Atrial Fibrillation >48 hours or unknown
    2. See Atrial Fibrillation Acute Management for <48 hour
  2. Delayed cardioversion
    1. Anticoagulation on Warfarin (or other Anticoagulant listed below) for 3 weeks
    2. Atrial Fibrillation Cardioversion
    3. Anticoagulation on Warfarin (or other Anticoagulant listed below) for 4 more weeks
  3. Early cardioversion
    1. Low Molecular Weight Heparin (LMWH) or Intravenous Standard Heparin for 24 hours
    2. Transesophageal Echocardiogram excludes atrial clot
    3. Atrial Fibrillation Cardioversion
    4. Anticoagulation on Coumadin (Warfarin) for 4 more weeks

V. Management: Warfarin

  1. Adverse Effects
    1. Risk of hemorrhagic complications are substantial
    2. Avoid in over age 80 (risk of Hemorrhagic CVA outweighs benefit)
    3. Consider Aspirin as alternative in lower risk patients and in advanced age
  2. Efficacy: Reduces Atrial Fib CVA risk
    1. Untreated: 3.6 to 7.4% risk of CVA/year
    2. Aspirin (325 qd): 2.5 to 3.6% risk of CVA/year
    3. Warfarin 0.9 to 3.5% risk of CVA/year
      1. Benefits outweigh bleeding risk if high risk
  3. Dosing
    1. See Warfarin Protocol
    2. Target INR 2-3
    3. Tight INR control is important
      1. INR 1.5-1.9 with 2 fold risk of severe CVA
      2. INR 1.5-1.9 with 3 fold risk of mortality
      3. Hylek (2003) N Engl J Med 349:1019-26 [PubMed]
  4. References
    1. Van Walraven (2002) JAMA 288:2441-8 [PubMed]

VI. Management: DOAC Alternatives to Warfarin in non-Valvular Atrial Fibrillation

  1. Indications
    1. First-Line Therapy
      1. Has largely replaced Warfarin for Atrial Fibrillation Anticoagulation in U.S.
    2. Warfarin Drug Interactions
    3. Warfarin drug level lability
    4. Patient refuses lab monitoring
  2. Contraindications (use Warfarin instead)
    1. See specific agents (Dabigatran, Rivaroxaban, Apixiban)
    2. End-stage renal disease (ESRD)
    3. Mechanical Heart Valves
    4. Cost prohibitive
  3. Disadvantages
    1. No proven reversal agent in case of bleeding
      1. See Anticoagulant Reversal
    2. Shorter half-lives (~12 hours) than Warfarin (40 hours)
      1. Atrial Fibrillation stroke risk returns after missing 2-3 doses of these agents
    3. Much more expensive than Warfarin
      1. Warfarin: $80/month (based on monthly INR monitoring)
      2. Other Anticoagulants: $250/month (approximate)
    4. More major Gastrointestinal Bleeding events than with Warfarin
      1. Dabigatran (Pradaxa) causes 8/1000 more major GI Bleeds than warafrin
      2. Rivaroxaban (Xarelto) also causes more GI Bleeding than Warfarin
      3. Apixaban (Eliquis) does NOT increase GI Bleeding risk when compared with Warfarin
  4. Medications (see specific agents for dosing protocols)
    1. Dabigatran (Pradaxa)
      1. Direct Thrombin Inhibitor
      2. Dabigatran 150 mg orally twice daily
        1. Decrease dose to 75 mg twice daily if GFR 15-30 (and avoid if GFR <15 ml/min)
      3. Fewer Drug Interactions Than Rivoroxaban
      4. More effective than Warfarin
        1. Prevents 3 more Ischemic CVAs and 6 more brain Hemorrhages per 1000 patients
    2. Factor Xa Inhibitors
      1. Apixaban (Eliquis)
        1. Dose: 5 mg orally twice daily
        2. Decrease dose to 2.5 mg if two of following present: age >80, weight <60 kg, Cr>1.5 mg/dl
        3. May be the preferred DOAC with best Atrial Fib efficacy and lowest adverse effect profile
              1. Lopez-Lopez (2017) BMJ 359:j5058 +PMID:29183961 -Proetti (2018) Stroke 49(1):98-106 +pmid:29167388 [PubMed]
      2. Rivaroxaban (Xarelto)
        1. Dose: 20 mg orally daily
        2. Decrease dose to 15mg daily if GFR 15-50 (and avoid if GFR <15 ml/min)
      3. Edoxaban (Savaysa)
        1. Dose: 60 mg orally daily
        2. Decrease dose to 30 mg daily if GFR15-50 (and avoid if GFR <15 ml/min)
        3. Also avoid if GFR>95 (enhanced clearance) or severe Cirrhosis (Child-Pugh Class C)
  5. References
    1. Steinberg (2014) BMJ 348:g2116 +PMID:24733535 [PubMed]

VII. Management: Aspirin

  1. Disadvantages
    1. For age over 75 years old, Aspirin 75 mg daily has same bleeding risk of Warfarin and higher risk of CVA
      1. Mant (2007) Lancet 370(9586):493-503 [PubMed]
    2. Clopidogrel with low dose Aspirin is not recommended for Atrial Fibrillation stroke prevention
      1. Has higher stroke risk and the same bleeding risk as Warfarin
  2. Current Indications
    1. NOT recommended for Atrial Fibrillation prevention of CVA
  3. Older Indications
    1. Low risk (Lone Atrial Fibrillation)
      1. Under age 60 years without Coronary Artery Disease
      2. Low risk of Thromboembolism (<.5% risk)
      3. Age >75 years without other Thromboembolism risk
    2. Risk of bleeding on Coumadin outweighs benefits
      1. See HAS-BLED Score
      2. See Outpatient Bleeding Risk Index
      3. Age >65 years
      4. History of Gastrointestinal Bleeding
      5. History of Cerebrovascular Accident
      6. Recent Myocardial Infarction
      7. Hematocrit <30%
      8. Creatinine >1.5
      9. Diabetes Mellitus
    3. References
      1. Man-Son-Hing (2002) Arch Intern Med 162:541-50 [PubMed]
  4. Dosing
    1. Aspirin 81 to 325 mg daily

VIII. Approach: Gastrointestinal Bleeding on Anticoagulants

  1. Background
    1. Gastrointestinal Bleeding occurs in 15% of patients on Anticoagulants for Atrial Fibrillation
  2. Management
    1. Restart Anticoagulation 7-14 days after Gastrointestinal Bleeding in CHADS2-VASc Score 2 or more
    2. Exceptions: cases in which restarting Anticoagulation would be too high risk
      1. Esophageal Varices
      2. Alcohol Abuse (especially if increased Liver Function Tests)
      3. Recurrent Gastrointestinal Bleeding history requiring hospital admission or Blood Transfusion
    3. Risk of stroke related mortality is 4x higher than mortality related to Gastrointestinal Bleeding
    4. Warfarin and especially Eliquis (Apixaban) have lower risk of Gastrointestinal Bleeding
    5. Pradaxa (Dabigatran) and Xarelto (Rivaroxaban) are higher risk for Gastrointestinal Bleeding
  3. Other preventive strategies
    1. Eliminate other risks for recurrent Gastrointestinal Bleeding (e.g. Alcohol, NSAIDs)
    2. Evaluate for Anticoagulation dosing errors
    3. Use Proton Pump Inhibitor for Gastrointestinal Prophylaxis
    4. Avoid combining Anticoagulant with Aspirin and Platelet ADP Receptor Antagonist (e.g. Plavix)
      1. Stopping Aspirin and switching to dual therapy (Anticoagulant and Clopidogrel) drops the bleeding risk 50% with similar efficacy
  4. References
    1. (2016) Presc Lett 23(2): 1
    2. (2022) Presc Lett 29(12): 68-9
    3. Chang (2015) BMJ 350:h1585 +PMID:25911526 [PubMed]
    4. Qureshi (2014) Am J Cardiol 113(4):662-8 +PMID:24355310 [PubMed]

IX. References

  1. (2014) Presc Lett 21(5): 25
  2. Casaletto (2014) Crit Dec Emerg Med 28(4): 10-19
  3. (2000) Circulation, 102(Suppl I):86-9
    1. http://www.circulationaha.org
  4. Albers (2001) Chest 119(1 suppl):S194-206 [PubMed]
  5. You (2012) Chest 141(2 Suppl):e531S-75S [PubMed]
  6. Stiell (2011) Canadian J Cardiol 27(1): 38-46 [PubMed]
  7. Wann (2011) Circulation 123(1): 104-23 [PubMed]
  8. King (2002) Am Fam Physician 66(2):249-56 [PubMed]
  9. Gutierrez (2011) Am Fam Physician 83(1): 61-8 [PubMed]
  10. Falk (2001) N Engl J Med 344:1067-78 [PubMed]
  11. Li (1998) Emerg Med Clin North Am 16:389-403 [PubMed]
  12. Lip (2015) JAMA 313(19):1950-6 +PMID:25988464 [PubMed]
  13. King (2002) Am Fam Physician 66:249-56 [PubMed]

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