PM&R News   •   April 2021

Purpose: To lower the risk of thromboembolism in patients with atrial fibrillation (A-fib).

• Risk reduction: ~70-75%
  • However, risk of severe bleeding: 0.2-0.4% risk/year (MC severe site: intracranial hemorrhage, ICH)
  • Lower than the risk of ischemic stroke in those with Afib
    • AF: determined via electrodiagnostic studies à EKG
      • “Irregularly, irregular” → RR intervals do not follow a pattern
      • [Usually] no definite P waves
        • If defined, P-P Interval is not regular; <200ms (atrial rate > 300 bpm)
• Epidemiology
  • S.: 3.03 million (2005); projected by 2050: 5.6-7.56 million (50%: > 80 y/o)
  • Worldwide: 33.5 million (2010)
  • Risk factors
    • Associated with underlying heart disease (Atrial enlargement (>50mm), elevated atrial pressure, or atrial inflammation/infiltration)
      • Hx of hypertensive heart disease
      • Hx of coronary heart disease
      • Rheumatic heart disease (uncommon in developed countries)
      • Valvular lesions that result in stenosis or regurgitation
      • Heart failure
      • Hypertrophic cardiomyopathy (10-28% risk)
      • Congenital heart disease: atrial septal defects (~20%; risk w/ age)
      • Others
        • Venous thromboembolic disease: DVT & PE
        • Obstructive sleep apnea
        • Obesity (BMI >30kg/m²)
        • Metabolic syndrome (HTN/DM/obesity + dyslipidemia)
        • Chronic kidney disease (GFR: 30-59)
        • Hyperthyroidism
        • Family hx (1^st degree relative)
        • Birth weight: direct relationship (Conen et. al 2010)
        • Excessive alcohol intake (new A-fib &/or triggers recurrence)
        • Inflammation: Elevated CRP levels (observational studies)
      • Triggers for recurrent A-fib (after new-onset A-fib)
        • cardiothoracic surgery (30%), infection (23%), non-cardiothoracic surgery (20%), acute myocardial infarction (18%), acute alcohol consumption, thyrotoxicosis, acute pericardial disease, acute pulmonary embolism, and other acute pulmonary pathology.
      • Prevalence increases with:
        • Advancing Age
        • Male gender
        • White race
        • Living in North America (lowest: Japan & South Korea)

• Indications
  • Risk of embolism [in those with AF] greater than the risk of bleeding
    • Non-valvular AF (NVAF): dependent on CHA2DS2-VASc score (Calculator¹ or Calculator² or App)
      • Females, CHA₂DS₂-VASc score of 1 or 0 in all patients: No anticoagulation
      • Males, CHA₂DS₂-VASc score of 1: Oral anticoagulation?
        • Dependent on risk factor present
        • Anticoagulation encouraged if the risk factor is: age 65-74 y/o
      • CHA₂DS₂-VASc score ≥2 (Non-valvular AF): Chronic anticoagulation
    • Valvular AF (mod-severe mitral valve stenosis or mechanical heart valves): Long-term anticoagulation recommended.
• Contraindications
  • Risks > benefits
    • Severe bleeding
    • [Recent] major surgery
    • Non-compliance with medical therapies
    • General anticoagulation contraindications
      • Absolute
        • Active bleeding
        • Severe bleeding diathesis
        • Recent, planned, or emergency high bleeding-risk surgery/procedure
        • Major trauma
        • Acute intracranial hemorrhage (ICH)
      • Relative
        • Recurrent bleeding from multiple gastrointestinal telangiectasias
        • Intracranial or spinal tumors
        • Large abdominal aortic aneurysm with concurrent severe hypertension
        • Stable aortic dissection
        • Recent, planned, or emergent low bleeding-risk surgery/procedure
        • Thrombocytopenia (specific groups/platelets counts in detail)
    • Labs:
      • Prior to anticoagulation: CBC, serum electrolytes, and assessment of renal function à especially in those on a non-vitamin oral anticoagulant.
    • Anti-thrombotic forms
      • Oral Anticoagulants (AC) > Aspirin
        • AC options:
          • warfarin
          • dabigatran, rivaroxaban, apixaban, or edoxaban (NOACs/DOACs)
• Treatment Recommendations
  • Non-valvular AF:
    • Oral direct thrombin inhibitor (DOAC; or non-vitamin K antagonist oral anticoagulant, NOAC) or a factor Xa inhibitor       >        warfarin
      • No preference with NOAC drug selection
      • Advantages: high relative/small absolute risk reduction of ICH, reduced dietary interactions, and significantly reduced drug interactions.
      • Disadvantages: lack of efficacy and safety data ( patients with chronic severe kidney disease), lack easy monitoring (blood levels and compliance), higher cost, and unforeseen [future] side effects.
    • When to choose warfarin (Bleeding risk score): INR target 0-3.0
      • Those already prescribed warfarin (INR: periodic checks and able to control levels; 65% of INRs within therapeutic range)
      • Chronic severe kidney disease (GFR <30 ; apixaban <25)
        • Edoxaban: contraindicated in a GFR > 95mL/min
      • Non-compliance with dosing of NOACs
      • Cost of NOACs
      • NOACs contraindicated (AEDs that induce enzyme activity, phenytoin; HIV patients on PI-based antiretrovirals)
    • Anticoagulant contraindication (except bleeding) → Aspirin, 75-100 mg daily + clopidogrel 75 mg daily
  • Valvular AF
    • Issues related to anticoagulation for AF in patients with these valvular lesions are not based on the CHA₂DS₂-VASc system.
    • Mechanical prosthetic valves (Helpful summary tables)
      • s/p mechanical valve implantation:
        • as soon as the risk of postoperative bleeding is considered acceptable, we suggest early bridging with heparin. Appropriate agents include intravenous unfractionated heparin (to achieve an activated partial thromboplastin time of 1.5 to 2 times the control value) or subcutaneous low molecular weight heparin (with antifactor Xa monitoring), continuing until the INR is at therapeutic levels for two consecutive days.
      • Non s/p mechanical prosthetic valves:
        • we recommend long-term treatment withwarfarin (or other VKA) and aspirin 75 to 100 mg/day rather than no antithrombotic therapy or VKA alone. The goal International Normalized Ratio (INR) varies with valve position and type and presence of thromboembolic risk factors.
        • Direct oral anticoagulants (DOACs) shouldnot be used in patients with mechanical valves.
      • Bioprosthetic aortic or mitral valve
        • we suggest use of early bridging anticoagulation as soon as the risk of postoperative bleeding is considered acceptable. We suggest treatment with UFH or LMWH until the INR is at therapeutic levels for two consecutive days.
        • we suggestaspirin 75 to 100 mg/day plus a VKA to achieve an INR of 2.5 for the first 3-6 to months. After the first three to six months, we suggest aspirin 75 to 100 mg/day (without VKA)
      • Transcatheter bioprosthetic aortic valves
        • A single antiplatelet agent plus an oral anticoagulant for three months à followed by an anticoagulant alone
        • An example regimen is the combination ofclopidogrel(300 mg loading dose followed by 75 mg daily) plus apixaban (dose based upon risk factors) for three months followed by apixaban alone.
      • Mitral stenosis
        • We recommend anticoagulation (with vitamin K antagonist; target International Normalized Ratio [INR] 2.5) in patients with moderate to severe rheumatic MS and one or more of the following conditions:
          • Atrial fibrillation (paroxysmal, persistent, or permanent)
            • Prior embolic event
            • Left atrial thrombus
• Dosing: determined by regulatory agencies or credible drug resources (Lexicomp). UTD specifics:
  • Dabigatran: 150 mg 2x/day
  •  Edoxaban
    • GFR: 50-95 → 60 mg 1x/day
    • GFR: 30-50 → 30 mg 1x/day
• Fun Facts
  • A-fib: MC cardiac arrythmia to reduce cardiac output & cause atrial thrombus formation
  • 5 A-fib classifications: new onset, paroxysmal, persistent, longstanding persistent, or permanent AF
  • AF typically reoccurs (unless intervened)
  • In those with paroxysmal AF: premature atrial complexes (premature atrial/supraventricular beats/complexes) can trigger A-fib
  • Each unit increase in BMI: 5% increase in A-fib risk (Framingham Heart Study)
  • CHA₂DS₂-VASc scores of 0, 1, and 2 correlate with [untreated] ischemic stroke risk of 0.2, 0.6, and 2.2, respectively.
  • Patients with mitral valve prostheses are at approximately twicethe risk  of developing embolization compared with those with aortic valve prostheses.

Photo by Yulia Matvienko on Unsplash

References:

1. https://www.uptodate.com/contents/new-onset-atrial-fibrillation?search=atrial%20fibrillation&sectionRank=2&usage_type=default&anchor=H461234558&source=machineLearning&selectedTitle=3~150&display_rank=3#H88477195
2. https://www.uptodate.com/contents/overview-of-the-treatment-of-lower-extremity-deep-vein-thrombosis-dvt?search=contraindication%20to%20anticoagulation&sectionRank=1&usage_type=default&anchor=H256309218&source=machineLearning&selectedTitle=1~150&display_rank=1#H256309218
3. https://www.uptodate.com/contents/overview-of-atrial-fibrillation?search=atrial%20fibrillation&sectionRank=3&usage_type=default&anchor=H356407304&source=machineLearning&selectedTitle=1~150&display_rank=1#H356407304
4. https://www.uptodate.com/contents/epidemiology-of-and-risk-factors-for-atrial-fibrillation?sectionName=PATHOGENESIS&search=atrial%20fibrillation&topicRef=1022&anchor=H7&source=see_link#H7
5. https://www.uptodate.com/contents/atrial-fibrillation-anticoagulant-therapy-to-prevent-thromboembolism?search=atrial%20fibrillation&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4#H451865217