03. Atrial Fibrillation

Resident Editor: Saate Shakil, MD

Faculty Editor: Katherine Julian, M.D.

BOTTOM LINE 

✔ Rate control with beta-blocker or CCB is supported by current data        

✔ Only indications for rhythm control: persistent symptoms or inability to rate control

✔ Goal HR<110 bpm           

Background

  • 2.2 million people in the United States have atrial fibrillation (AF), median age 75 years. AF doubles the risk of death.
  • The prevalence of AF is 2.3% in patients > 40 years old and 5.9% in those > 65 years old. Approximately 70% of patients with AF are 65 to 85 years old.
  • Associated with cardiovascular disease (HTN, CAD, CHF, cardiomyopathy, valvular disease), pulmonary disease, obstructive sleep apnea, excessive ETOH intake, hyperthyroidism, stroke, DM, PVD
  • Classification:
    • Paroxysmal (i.e. self-terminating): episodes terminate spontaneously in less than seven days, usually less than 48 hour
    • Persistent: fails to self-terminate within 7 days
    • Long-standing persistent: fails to self-terminate for >1 year
    • Permanent: continuing for >1 year and cardioversion either has not been attempted or has failed. In addition, patient has accepted diagnosis and the decision has been made to not attempt to restore or maintain sinus rhythm.
    • "Lone": paroxysmal, persistent, or permanent AF in patients without structural heart disease (including HTN). Think of this as “low risk” AF, as these patients lack the risk factors defined below under Treatment. This term is now rarely used due to limited clinical utility.

Signs and Symptoms

  • Often asymptomatic, but can include palpitations, chest pain, fatigue, dyspnea, syncope, lightheadedness, polyuria (post-tachycardia diuresis due to increased atrial natriuretic peptide).
  • History – Symptomatic? Severity? Frequency? Duration (if documented<48 hours can cardiovert, anticoagulate 4 weeks after)? Alcohol? FH? Other associated conditions (ex: HTN, CAD, HF, PVD, CVD, DM, COPD, stroke)?

Evaluation

  • Physical – be sure to look for signs of embolic phenomena, hyperthyroidism, valvular disease.
  • Labs/tests – EKG (establishes diagnosis), TTE, TFTs, Cr, LFTs.  Can also do BP, CBC, FBS, urine protein if otherwise indicated. Consider ambulatory cardiac monitoring if symptoms are paroxysmal, and rhythm not captured on EKG in clinic. 
  • Warrants aggressive workup and treatment of coronary artery disease risk factors given high co-incidence (lipids, fasting blood glucose, HgbA1c; consider stress test).
  • There are currently no guidelines to support screening in asymptomatic individuals.

Treatment

A. Rate vs. rhythm control (key trials: AFFIRM, RACE) 

  • Rate control equivalent to rhythm control in mortality, quality of life; rhythm control group had more hospitalizations and more adverse drug effects
  • Choice of agent: beta blocker (atenolol, metoprolol) or calcium channel blocker (verapamil, diltiazem) first line. Digoxin 2nd line as it does not prevent tachycardia with exertion. Avoid calcium channel blocker in patients with heart failure.
  • Goal HR: In the AFFIRM trial, HR goal was <80 bpm at rest, <110 during a 6 minute walk, and average <100 on 24h Holter monitoring. Guidelines suggest <110 bpm acceptable if no symptoms and EF >40%.
  • In younger, more active patients with AF, exercise ECG may be necessary to assess HR control during exertion.
  • When to consider rhythm control: symptoms despite rate control, young patients (AFFIRM enrolled only patients 65 years or older), reversible cause of AF.

B. Anticoagulation for stroke prevention

  • AF imparts a relative risk of stroke of 2.4 for men and 3.0 for women compared to non-AF populations. Anticoagulation is the only treatment shown to decrease mortality. 
  • Selection of antithrombotic irrespective of whether pattern is paroxysmal, persistent, or permanent must be individualized and based on shared decision making after discussion of risks of stroke and bleeding and patient’s preferences.
  • Whom to anticoagulate: 2014 ACC/AHA guidelines recommend use of CHA2DS2-VASC. Note: these classification schemes are for NON-VALVULAR AF. If valvular AF, patients should be anti-coagulated with warfarin.

BOTTOM LINE            

✔ Warfarin is superior to antiplatelet therapy in all but lowest risk (CHADS2 = zero)       

✔ Stroke risk and warfarin efficacy similar for paroxysmal and persistent AF

✔ If going to anti-coagulate, consider warfarin or NOACs

✔ Both rate and rhythm controlled patients need anticoagulation

✔ Use CHA2DS2-VASC to determine whom to anticoagulate       

CHA2DS2-VASC scoring for anticoagulation risk stratification

Clinical Parameter

Points

Congestive heart failure/LV dysfunction

1

Hypertension

1

Age >75

2

Diabetes mellitus

1

Secondary prevention 

(history of TIA, stroke or VTE)

2

Vascular disease (ex: prior MI)

1

Age 65-74 years

1

Female

1
  • CHAD2DS2-VASC score 0: No antithrombotic therapy is recommended
  • CHAD2DS2-VASC score 1: No antithrombotic therapy or treatment with an oral anticoagulant or aspirin may be considered 
  • CHAD2DS2-VASC score >2: Anticoagulation strongly recommended

HAS-BLED scoring system to estimate bleeding risk 

Clinical Parameter

Points

Hypertension

1

Anormal liver and/or renal function (1 pt each)

1 or 2

Stroke

2

Bleeding tendency or predisoposition

1

Labile INRs (for patients on warfarin) 

2

Elderly (>65)

1

Drugs (concomitant ASA or NSAIDs) or excess ETOH use (1 pt each) 

1 or 2
  • HAS-BLED score >3 indicates “high risk” for bleeding; 
  • Though the 2014 AHA/ACC guidelines recommend using the HAS-BLED score to identify those at “high risk” for bleeding, the scoring system has poor predictive accuracy.

C. Types of Anticoagulation

  • Warfarin: Studied in numerous trials.  Overall, reduces risk of stroke by two thirds compared to no anti-thrombotic therapy. Requires ongoing monitoring of INR. Use for valvular AF. 
    • If AF + indication for dual antiplatelet therapy (recent PCI/MI), consider omitting ASA and using warfarin + P2Y12 inhibitor (WOEST trial; only clopidogrel studied)
  • Direct Antagonist Oral Anticoagulants (DOACs): Can use direct oral anticoagulants as first line agents. However, there are some key considerations: (1) premature discontinuation (in AF trials) increases risk of thrombotic events so bridge with heparin if changing NOAC to warfarin; (2) all have hematoma risk in patients receiving spinal/epidural procedures; (3) decline in renal function leads to increased bleeding risk, so should check renal function minimum yearly and more often in DOACs that are renally cleared; (4) do not use with mechanical heart valves (not yet studied).
    • Dabigatran (oral direct thrombin inhibitor): 150 mg bid superior to warfarin (RE-LY) in preventing strokes. 
      • Advantages: no INR monitoring, fewer dietary/drug interaction. 
      • Disadvantages: lack of reversing agent, lack of long-term safety data, shorter half-life (noncompliant patients may not remain anticoagulated), increased GI bleed/dyspepsia risk.  May increase cardiac risk (so caution if CAD). Cannot use if severely impaired renal function. Do not use with mechanical heart valves (excess thromboembolic and bleeding risk in the RE-ALIGN trial).
    • Rivaroxaban (oral Xa inhibitor): non-inferior to warfarin in ROCKET AF trial. 20mg daily if CrCl>50. Similar advantages/disadvantages as dabigatran but once daily dosing. May interact with diltiazem, verapamil, amiodarone. Caution with impaired renal function.
    • Apixaban (oral Xa inhibitor): 5 mg BID, non-inferior to warfarin in ARISTOTLE trial. Similar advantages/disadvantages as rivaroxaban. Dose adjustment (2.5 mg BID) required if any TWO of the following ≥80 y, body weight ≤60 kg, serum Cr ≥1.5. Caution with further impaired renal function. 
    • Edoxaban (oral Xa inhibitor): non-inferior to warfarin in ENGAGE-AF trial. 60mg daily; in contrast to the other DOACs, do NOT use edoxaban if CrCl ≥95; in the ENGAGE-AF trial, these patients had an increased rate of ischemic stroke compared with patients on warfarin.

When to refer​

  • Refer to Cardiology/EP for cardioversion: 
    • If symptoms are unrelieved despite adequate rate control,
    • If unable to achieve rate control, 
    • If complications occur, 
    • If patient is otherwise young (recall that the AFFIRM trial only enrolled patients 65 years or older) and healthy with first episode of AF (more likely to maintain sinus rhythm after cardioversion and to benefit from avoidance of lifelong anticoagulation), 
    • If ablation is desired, 
    • In pregnant women, and 
    • In Wolf-Parkinson-White (WPW)

​​References

Dewilde, Willem JM, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. The Lancet 381.9872 (2013): 1107-1115.

Eikelboom, John W., et al. Dabigatran versus warfarin in patients with mechanical heart valves.  New England Journal of Medicine 369.13 (2013): 1206-1214.

Gage BF et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001, 13;285(22): 2864-70. 

Giugliano, Robert P., Christian T. Ruff, Eugene Braunwald, Sabina A. Murphy, Stephen D. Wiviott, Jonathan L. Halperin, Albert L. Waldo et al. Edoxaban versus warfarin in patients with atrial fibrillation. New England Journal of Medicine 369, no. 22 (2013): 2093-2104.

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Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the long- term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am J Med. 2002;113:359–364.

The Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Guidelines for the management of atrial fibrillation. Europace. 2010;12: 1360–1420.

Wyse, DG et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. The atrial fibrillation follow-up investigation of rhythm management (AFFIRM) investigators. N Engl J Med. 2002;347: 1825.