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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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slide1
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

slide2
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

slide3
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

slide4
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

slide5
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

slide7

Case 1

55-year-old male with lone

atrial fibrillation

case 1
Case 1

55-year-old male comes to the office stating that he has had two days of palpitations. He denies chest pain or shortness of breath.

Past medical history: negative

Medications: none

Family history: father died of an MI at 80 years of age; mother is alive and well

case 1 continued
Case 1 (continued)

Social history: works as a financial advisor, no tobacco use, social drinker (few drinks a week)

Physical exam:

Pulse: 105 irregular

BP: 130/74 mm Hg

Respiratory rate: 14

CV: irregularly irregular without murmurs

Lungs: clear

Electrocardiogram: atrial fibrillation at rate of 104

chads2 scoring
CHADS2 Scoring

CHF = congestive heart failure; TIA = transient ischemic attack.

Information from Gage BF, et al. JAMA 2001;285:2864-70.

chads2 application
CHADS2 Application

Information from Gage BF, et al. JAMA 2001;285:2864-70.

chads2 and recommended therapy
CHADS2 and Recommended 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.

aspirin
Aspirin

Stroke reduction compared with placebo

Aspirin: 14% to 22%

Warfarin: 62%

Bleeding risk

Aspirin: 1.3 per 100 patient years (lethal bleeding = 0.2)

Warfarin: 2.2 per 100 patient years (lethal bleeding = 0.4)

Hart RG, et al. Ann Intern Med 1999;131:492-501.

EAFT Study Group. Lancet 1993;342:1255-62.

Petersen P, et al. Lancet 1989;333:175-9.

Van Walraven C, et al. JAMA 2002;288:2441-8.

Gulløv AL, et al. Arch Intern Med 1999;159:1322-8.

slide15
Recommendation #1: The CHADS2 score is recommended as a simple initial means of assessing stroke risk in nonvalvular atrial fibrillation (AF). (I A)

Recommendation #2: Patients with no risk factors (essentially patients aged <65 years with lone AF, with none of the risk factors) are at low risk of stroke. In these patients, the use of aspirin, 75 mg–325 mg daily, or no antithrombotic therapy, is recommended. (I B)

Evidence-based Recommendations

ESC. European Heart Journal 2010;31:2369‑429.

slide16
Recommendation #3: Antithrombotic therapy to prevent thromboembolism is recommended for all patients with AF, except those with lone AF or contraindications. (I A)

Evidence-based Recommendation

ACC/AHA/ESC. Circulation 2006;114:e257-354.

slide18

Case 2

65-year-old male with hypertension

case 2
Case 2

65-year-old male with a history of hypertension presents for routine follow-up and is noted to have an irregular pulse. He denies chest pain or shortness of breath.

Past medical history

Hypertension

Peptic ulcer disease treated approximately 5 years ago

Intermittent GERD

Medications

Hydrochlorothiazide, 12.5 mg daily

Lisinopril, 5 mg daily

Omeprazole OTC, 10 mg as needed

case 2 continued
Case 2 (continued)

Social history: retired schoolteacher, denies tobacco use, rare alcohol use

Physical exam:

General: alert, oriented, comfortable

Pulse: 95

BP: 138/86 mm Hg

CV: irregularly irregular with 2/6 systolicblowing murmur at the apex

Electrocardiogram: atrial fibrillation with a heart rate of 95, possible left ventricular hypertrophy

mortality rhythm vs rate control affirm trial
Mortality: Rhythm vs. Rate Control (AFFIRM trial)

30

25

20

15

10

5

0

P=0.08

Management with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy.

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.

chads2 and recommended therapy1
CHADS2 and Recommended 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.

stroke systemic embolization dabigatran vs warfarin
Stroke/Systemic Embolization: Dabigatran vs. Warfarin

Figure shows data from the RE-LY study, displaying cumulative hazard rates for the primary outcome of stroke or systemic embolism.

Primary outcome results

Warfarin = 1.69% per year

Dabigatran (150 mg twice daily) = 1.11% per year

(P<0.001 for superiority; RR: 0.66)

Rates of major bleeding

Warfarin = 3.36% per year

Dabigatran (150 mg twice daily) = 3.11% per year

(P=0.31)

0.05

0.04

0.03

0.02

0.01

0.00

Warfarin

Dabigatran

110 mg

Cumulative Hazard Rate

Dabigatran

150 mg

0 6 12 18 24 30

Months

RE-LY = The Randomized Evaluation of Long-Term Anticoagulation Therapy.

Reprinted with permission from Connolly S, et al. N Engl J Med 2009;361:1139-51.

comparing dabigatran and warfarin
Comparing Dabigatran and Warfarin

U.S. prescribing information for dabigatran and warfarin, 2010.

slide26
Recommendation #4: Anticoagulation is recommended for patients with more than one moderate risk factor. Such risk factors include age 75 years or greater, hypertension, heart failure, impaired left ventricular systolic function (ejection fraction 35% or less, or fractional shortening less than 25%), and diabetes mellitus. (I A)

Evidence-based Recommendation

ACC/AHA/ESC. Circulation 2006;114:e257-354.

slide27

Case 3

70-year-old female

case 3
Case 3

70-year-old female presents with two weeks of palpitations without shortness of breath or chest pain.

Past medical history

Hypertension

Hypercholesterolemia

Congestive heart failure (ejection fraction: 35%)

Medications

Metoprolol, 50 mg twice daily

Lisinopril, 20 mg daily

Atorvastatin, 20 mg daily

case 3 continued
Case 3 (continued)

Social history: lives with her husband, neither drives; does not smoke or use alcohol

Physical exam:

General: alert, interactive, comfortable

BP: 128/78 mm Hg

Pulse: 80

RR: 16

Lungs: clear

CV: irregularly irregular with II/VI systolic murmur left upper sternal border

Electrocardiogram: atrial fibrillation with rate 76

rate vs rhythm control in chf
Rate vs. Rhythm Control in CHF

Kaplan–Meier Estimates of Death from Cardiovascular Causes (Primary Outcome)

100

80

60

40

20

0

Rate Control

  • Similar outcomes to AFFIRM
  • No evidence-based benefit of rhythm control over rate control in CHF
    • No survival advantage
    • No outcomes advantage

Rhythm Control

Survival Rate (%)

P=0.59

0 12 24 36 48 60

Months of Follow-up

  • Reprinted with permission from Roy D, et al. N Engl J Med 2008;358:2667-77.
dabigatran practical aspects
Dabigatran: Practical Aspects

Dosing and creatinine clearance

>30 ml/min: 150 mg twice daily

15-30 ml/min: 75 mg twice daily

<15 ml/min: Do not use

No need for blood level monitoring

Therapeutic level reached within 30 minutes to 2 hours

U.S. prescribing information for dabigatran, 2010.

dabigatran practical aspects continued
Dabigatran: Practical Aspects (continued)
  • Switching from warfarin to dabigatran
    • Not much guidance yet available
    • Wait until INR is below 2.0, then start dabigatran
  • Surgery
    • Creatinine clearance ≥50 ml/min: Skip doses for 1-2 days before surgery
    • Creatinine clearance <50 ml/min: Skip doses for 3-5 days before surgery

U.S. prescribing information for dabigatran, 2010.

slide34
Recommendation #5: In patients with atrial fibrillation (AF), including those with paroxysmal AF, who have two or more of the following risk factors for future ischemic stroke, the guidelines recommend long-term anticoagulation with an oral vitamin K antagonist, such as warfarin, targeted at an INR of 2.5 (range: 2.0 to 3.0) because of the increased risk of future ischemic stroke faced by this set of patients. (1A)

Risk factors: Age >75 years, history of hypertension, diabetes mellitus, and moderately or severely impaired left ventricular systolic function and/or heart failure

Evidence-based Recommendation

ACCP. Chest 2008;133(Suppl 6):546S-92S.

slide35
Recommendation #6: Dabigatran is useful as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal to permanent atrial fibrillation and risk factors for stroke and systemic thromboembolism who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance <15ml/min), or advanced liver disease (impaired baseline clotting function). (I B)

Evidence-based Recommendation

ACCF/AHA/HRS. J Am Coll Cardiol 2011;57:1330-7.

slide37

Case 4

85-year-old female with multiple comorbidities

case 4
Case 4

85-year-old female presents for routine physical exam. She has no complaints, and denies chest pain or shortness of breath.

Past medical history

Hypertension

Coronary artery disease

Congestive heart failure

Degenerative joint disease with ambulatory dysfunction

case 4 continued
Case 4 (continued)

Medications

Atenolol, 25 mg daily

Lisinopril, 10 mg daily

Hydrochlorothiazide, 12.5 mg daily

Aspirin, 81 mg daily

Social history: lives in assisted living and has had numerous falls in past six months; does not smoke or drink alcohol

case 4 continued1
Case 4 (continued)

Physical exam

General: comfortable and interactive

BP: 130/80 mm Hg

Pulse: 80

Lungs: clear

CV: irregularly irregular with I/VI systolic murmur

Electrocardiogram: atrial fibrillation with rate 104

slide41

Aspirin Plus Clopidogrel (ACTIVE A Trial)

  • Aspirin (75 mg-100 mg daily) plus clopidogrel (75 mg daily) reduced stroke risk by 28%
    • Aspirin stroke risk: 3.3% per year
    • Combination therapy stroke risk: 2.4% per year
  • 2.0% per year incidence of major bleeding (vs. 1.3% with aspirin alone)

1.0

0.8

0.6

0.4

0.2

0.0

Cumulative Incidence

P<0.001

Aspirin Only

Clopidogrel Plus Aspirin

0 1 2 3 4

Years

Adapted with permission from Connolly S. N Engl J Med 2009;360:2066-78.

slide42
Recommendation #7: The selection of antithrombotic agent should be based on the absolute risks of stroke and bleeding, and the relative risk and benefit for a given patient. (I A)

Evidence-based Recommendation

ACC/AHA/ESC. Circulation 2006;114:e257-354.

slide43
Recommendation #8: 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.

final comments rate vs rhythm
Final Comments: Rate vs. Rhythm

There is no significant difference in outcomes for patients, either with or without congestive heart failure, with a strategy of either rate control or rhythm control.

Roy D, et al. N Engl J Med 2008;358:2667-77.

Wyse DG, et al. N Engl J Med 2002;347:1825-33.

final comments thromboprophylaxis
Final Comments: Thromboprophylaxis

Assess ALL patients with atrial fibrillation for risk of stroke

Patients with low risk of stroke (CHADS2 score = 0): do not need anticoagulation and may be managed with an antiplatelet agent

All others need anticoagulation, unless there are contraindications

Patients with moderate risk (CHADS2 score = 1): either an antiplatelet or anticoagulation agent is appropriate

thromboprophylaxis continued
Thromboprophylaxis (continued)

For patients in whom anticoagulation is contraindicated, an antiplatelet agent is recommended:

Either aspirin or clopidogrel

There may also be a place for the combination of aspirin plus clopidogrel

Combination decreases risk of stroke but increases risk of major bleeds compared to aspirin alone (Connolly S. N Engl J Med 2009;360:2066-78.)

thromboprophylaxis continued1
Thromboprophylaxis (continued)
  • Patients with CHADS2 score ≥2 – or patients with score of 1 in whom anticoagulation is indicated – two anticoagulant agents are available.
    • Dabigatran
    • Warfarin
thromboprophylaxis continued2
Thromboprophylaxis (continued)
  • Decision of which anticoagulant medication to use should be made on an individual basis
    • Dabigatran has lower risk of stroke and systemic embolism compared with warfarin
    • Same major bleeding risk at 150 mg twice daily

Connolly SJ, et al. N Engl J Med 2009;361:1139-51.

Wann LS, et al. Circulation 2011;123:1144-50.