Atrial Fibrillation Atrial Fibrillation Evidence Based CareEvidence Based Care

20112011

Allan Anderson, MD, FACC, FAHAAllan Anderson, MD, FACC, FAHA

Division of CardiologyDivision of Cardiology

Projection for Prevalence of Atrial Fibrillation: 5.6 Million by 2050

Go AS et al. JAMA. 2001;285:2370-2375.

2.662.94

3.33

3.80

4.34

4.785.16

5.42 5.61

2.08

Ad

ult

s w

ith

atr

ial

fib

rillati

on

in

million

s

1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050

0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

Projected number of adults with atrial fibrillation in the United States between 1995 and 2050

Upper and lower curves represent the upper and lower scenarios based on sensitivity analyses.

Years

2.262.44

Atrial Fibrillation Is Associated With Increased Mortality

0

10

20

30

40

50

60

70

80 With atrial fibrillation Without atrial fibrillation

Cu

mu

lati

ve m

ort

ality

over

3 y

ears

(%

)

Men Women Men Women Men Women

65-74 years of age 75-84 years of age 85-89 years of age

38.6

30.2*34.0

25.4*

54.5

47.4* 47.5

36.1*

71.365.1*

62.4

51.0*

* Significantly different from patients with atrial fibrillation (P<.05).Wolf PA et al. Arch Intern Med. 1998;158:229-234.

Atrial Fibrillation: Major Cause of Stroke in the

United States 15% of all strokes attributable to atrial fibrillation

75,000 strokes per year attributable to atrial fibrillation

3- to 5-fold increase in risk of stroke in patients with atrial fibrillation

Stroke risk persists even in asymptomatic atrial fibrillation

Go AS et al. JAMA. 2001;285:2370-2375; Go AS. Am J Geriatr Cardiol. 2005;14:56-61; Wolf PA et al. Stroke. 1991;22:983-988; Benjamin EJ et al. Circulation. 1998;98:946-952; Page RL et al. Circulation. 2003;107:1141-1145.

Age (years) 85+ 35 to 5475 to 84 65 to 74 55 to 64

Pre

vale

nce p

er

10

,00

0 p

ers

on

sIncreasing Hospitalizations in the United States

When Atrial Fibrillation Is Principal Diagnosis(National Hospital Discharge Survey)

Wattigney WA et al. Circulation. 2003;108:711-716.

Year

1985 1987 1989 1991 1993 1995 1997 1999

0

20

40

60

80

100

120

140

Atrial Fibrillation Adversely Affects Quality of Life (QoL)

Lower scores = poorer QoL

Dorian P et al. J Am Coll Cardiol. 2000;36:1303-1309.

SF-3

6 s

core

54

68 71 68

59

70

85

7678

8892

81

0

20

40

60

80

100

120

General health Physicalfunction

Social function Mental health

Atrial fi brillation

Post myocardialinfarction

Controls

Famous FibrillatorsFamous Fibrillators

Famous FibrillatorsFamous Fibrillators

Famous FibrillatorsFamous Fibrillators

Famous FibrillatorsFamous Fibrillators

Famous FibrillatorsFamous Fibrillators

Famous FibrillatorsFamous Fibrillators

Famous FibrillatorsFamous Fibrillators

Atrial FibrillationAtrial Fibrillation20112011

Patterns of AFPatterns of AF Evaluation of PatientEvaluation of Patient Evidence BaseEvidence Base

Rate ManagementRate Management Rhythm ManagementRhythm Management Prevention of thromboembolismPrevention of thromboembolism

New stuffNew stuff

Patterns of Atrial Fibrillation

Fuster, V. et al. J Am Coll Cardiol 2011;57:e101-e198

First Detected

Paroxysmal(Self terminating)

Persistent(Non self terminating)

Permanent

Atrial FibrillationEvaluation of Patients

History and physical examination Presence and nature of associated symptoms Clinical type (1st episode, paroxysmal,

persistent, permanent) Onset/date of discovery of 1st episode Frequency, duration, precipitating factors,

mode of termination Response to therapies Establish underlying heart disease or other

treatable conditions (e.g., hyperthyroidism, alcohol)

Atrial FibrillationEvaluation of Patients

ECG Verify rhythm LVH? Pre-excitation (WPW)? Bundle branch block? Prior MI? Measure and follow intervals (R-R, QRS,

QT) in conjunction with drug therapy

Atrial FibrillationEvaluation of Patients

Transthoracic echocardiogram Valvular disease Chamber sizes/ventricular function Peak RV systolic pressure (pulmonary

hypertension) LVH Pericardial disease Atrial clot (usually not helpful, requires TEE)

Atrial FibrillationEvaluation of Patients

Other studies 6 minute walk test: evaluate adequacy of rate control Stress test

Adequacy of rate control Reproduce exercise-induced AF Presence of ischemia (regarding use of IC drugs)

Holter monitor Verify/establish diagnosis Adequacy of rate and/or rhythm control

Transesophageal echocardiogram (TEE) LA clot Guide to cardioversion (expedited)

The Guidelines

Class I: Conditions for which there is evidence and/or general agreement that a given procedure/therapy is beneficial, useful, and effective.

Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of performing the procedure/therapy.

IIA: Weight of evidence/opinion is in favor of usefulness/efficacy.

IIB: Usefulness/efficacy is less well established by evidence/opinion.

Class III: Conditions for which there is evidence and/or general agreement that a procedure/therapy is not useful or effective and in some cases may be harmful.

Level of Evidence

A: Data derived from multiple randomized clinical trials or meta-analyses.

B: Data derived from a single randomized trial, or nonrandomized studies.

C: Only consensus opinion of experts, case studies, or standard-of-care.

Expert OpinionExpert Opinion

One who knows enough jargon to be both confusing and dangerous.

Ambrose Bierce1842-1913

ConsensusConsensus General agreement within a General agreement within a

group, especially after protracted, group, especially after protracted, lengthy, bitter debate and loss of lengthy, bitter debate and loss of life.life.

Opinion obtained by straw polling Opinion obtained by straw polling when the opposition is not when the opposition is not present. See team building. present. See team building.

The current thinking of the team The current thinking of the team supervisor. supervisor.

Rate or Rhythm Control?Rate or Rhythm Control?

Comparison of TrialsRate vs. Rhythm Control

TrialPatient

s (n)

AF Duratio

n

Patients in SR

*

Stroke/Embolism Death

RateRhyth

m RateRhyth

m

 

AFFIRM (2002)

4060 35% vs. 63% (at 5 y)

88/2027 93/2033 310/2027 356/2033

RACE (2002)

522 1 to 399 d 10% vs. 39% (at 2.3 y)

7/256 16/266 18/256 18/266

PIAF (2000)

252 7 to 360 d 10% vs. 56% (at 1 y)

0/125 2/127 2/125 2/127

STAF (2003)

200 6±3 mo 11% vs. 26% (at 2 y)

2/100 5/100 8/100 4/100

HOT CAFÉ (2004)

205 7 to 730 d NR vs. 64%

1/101 3/104 1/101 3/104

NR

Clinical Events

Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient

versus Strict Rate Control II RACE II

614 patients with permanent AF (age </= 80)

Lenient rate control (HR<110 at rest) OR Strict rate control

HR < 80 at rest, AND HR < 110 during moderate exercise

Composite outcome: CV death, hospitalization for HF, systemic embolism, bleeding, life-threatening arrhythmia

Follow-up: At least 2 years; maximum – 3 years Van Gelder IC, Groenveld HF, Crijns HJ, et al. N

Engl J Med 2010;362:1363-1373.

Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient

versus Strict Rate Control II RACE II

3 year cumulative incidence of primary outcome 12.9% - lenient 14.9% - strict

Target HR goal(s) 304 (97.7%) – lenient 204 (67%) – strict

Total Visits 75 – lenient 684 - strict

Van Gelder IC, Groenveld HF, Crijns HJ, et

al. N Engl J Med 2010;362:1363-1373.

P < 0.001

P < 0.001

P < 0.001

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Pharmacologic Rate Control (Class I) Measurement of the heart rate at rest

and control of the rate using pharmacological agents (either a beta blocker or non-dihydropyridine calcium channel antagonist, in most cases) are recommended for patients with persistent or permanent AF. (Level of Evidence: B)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Pharmacologic Rate Control (Class I) In the absence of pre-excitation,

intravenous administration of beta blockers (esmolol, metoprolol, or propranolol) or non-dihydropyridine calcium channel antagonists (verapamil, diltiazem) is recommended to slow the ventricular response to AF in the acute setting, exercising caution in patients with hypotension or HF. (Level of Evidence: B)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Pharmacologic Rate Control (Class I) Intravenous administration of

digoxin or amiodarone is recommended to control the heart rate in patients with AF and HF who do not have an accessory pathway. (Level of Evidence: B)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Pharmacologic Rate Control (Class I) In patients who experience symptoms

related to AF during activity, the adequacy of heart rate control should be assessed during exercise, adjusting pharmacological treatment as necessary to keep the rate in the physiological range. (Level of Evidence: C)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Pharmacologic Rate Control (Class I) Digoxin is effective following oral

administration to control the heart rate at rest in patients with AF and is indicated for patients with HF, LV dysfunction, or for sedentary individuals. (Level of Evidence: C)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt Not’s”The “Thou Shalt Not’s”

Pharmacologic Rate Control (Class III) Digitalis should not be used as the sole

agent to control the rate of ventricular response in patients with paroxysmal AF. (Level of Evidence: B)

Catheter ablation of the AV node should not be attempted without a prior trial of medication to control the ventricular rate in patients with AF. (Level of Evidence: C)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt Not’s”The “Thou Shalt Not’s”

Pharmacologic Rate Control (Class III) In patients with decompensated HF and AF,

intravenous administration of a non-dihydropyridine calcium channel antagonist may exacerbate hemodynamic compromise and is not recommended. (Level of Evidence: C)

Intravenous administration of digitalis glycosides or non-dihydropyridine calcium channel antagonists to patients with AF and a pre-excitation syndrome may paradoxically accelerate the ventricular response and is not recommended. (Level of Evidence: C)

Wann, L. S. et al. J Am Coll Cardiol 2011;57:223-242

Therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial

fibrillation

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Maintenance of sinus rhythm (Class I) Before initiating anti-arrhythmic drug

therapy, treatment of precipitating or reversible causes of AF is recommended. (Level of Evidence: C)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt Not’s”The “Thou Shalt Not’s”

Maintenance of sinus rhythm (Class III) Antiarrhythmic therapy with a particular drug is

not recommended for maintenance of sinus rhythm in patients with AF who have well-defined risk factors for proarrhythmia with that agent. (Level of Evidence: A)

Pharmacological therapy is not recommended for maintenance of sinus rhythm in patients with advanced sinus node disease or AV node dysfunction unless they have a functioning electronic cardiac pacemaker. (Level of Evidence: C)

Prevention of Prevention of ThromboembolismThromboembolism

Effects on all stroke (ischemic and hemorrhagic) of therapies for patients with

atrial fibrillation

Stroke Risk Prediction in AFCHADS2 Criteria

CRITERIA SCORE

Prior stroke or TIA 2

Age > 75 years 1

Hypertension 1

Diabetes Mellitus 1

Heart Failure 1

Walraven WC et al. JAMA 2001;285:2864–70 (426).

Stroke Risk Prediction in AFCHADS2 Criteria

Patients 1733

Adjusted stroke rate/yr with 95% CI

CHADS2 Score

120 1.9 (1.2 -3.0) 0 463 2.8 (2.0-3.8) 1 523 4.0 (3.1-5.1) 2 337 5.9 (4.6-7.3) 3 220 8.5 (6.3-11.1) 4 65 12.5 (8.5-17.5) 5 5 18.2 (10.5 –

27.4) 6

Walraven WC et al. JAMA 2001;285:2864–70 (426).

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Prevention of thromboembolism (Class I) Antithrombotic therapy to prevent

thromboembolism is recommended for all patients with AF, except those with lone AF or contraindications. (Level of Evidence: A)

The selection of the antithrombotic agent should be based upon the absolute risks of stroke and bleeding and the relative risk and benefit for a given patient. (Level of Evidence: A)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Prevention of thromboembolism (Class I) For patients without mechanical heart valves at high

risk of stroke, chronic oral anticoagulant therapy with a vitamin K antagonist is recommended in a dose adjusted to achieve the target intensity INR of 2.0 to 3.0, unless contraindicated. Factors associated with highest risk for stroke in patients with AF are prior thromboembolism (stroke, TIA, or systemic embolism) and rheumatic mitral stenosis. (Level of Evidence: A)

Anticoagulation with a vitamin K antagonist is recommended for patients with more than 1 moderate risk factor. Such factors include age 75 y or greater, hypertension, HF, impaired LV systolic function (ejection fraction 35% or less or fractional shortening less than 25%), and diabetes mellitus. (Level of Evidence: A)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt’s”The “Thou Shalt’s”

Prevention of thromboembolism (Class I) INR should be determined at least weekly during initiation of

therapy and monthly when anticoagulation is stable. (Level of Evidence: A)

Aspirin, 81–325 mg daily, is recommended as an alternative to vitamin K antagonists in low-risk patients or in those with contraindications to oral anticoagulation. (Level of Evidence: A)

For patients with AF who have mechanical heart valves, the target intensity of anticoagulation should be based on the type of prosthesis, maintaining an INR of at least 2.5. (Level of Evidence: B)

Antithrombotic therapy is recommended for patients with atrial flutter as for those with AF. (Level of Evidence: C)

Atrial FibrillationAtrial FibrillationThe “Thou Shalt Not’s”The “Thou Shalt Not’s”

Prevention of thromboembolism (Class III) Long-term anticoagulation with a

vitamin K antagonist is not recommended for primary prevention of stroke in patients below the age of 60 y without heart disease (lone AF) or any risk factors for thromboembolism. (Level of Evidence: C)

Dabigatran (Pradaxa)

Direct thrombin inhibitor Dose:

CrCl > 30: 150 mg twice daily CrCl < 30: 75 mg twice daily

See prescribing information on transitions between warfarin or parenteral anticoagulants

Dabigatran (Pradaxa)

1.5 % risk of life threatening bleeding vs. 1.8% for warfarin (RE-LY)

Avoid with Rifampin (P-gp inducer) Pregnancy Class C Major side effects: bleeding;

gastrointestinal

Dabigatran versus Warfarin in Patients with Atrial Fibrillation

RE-LY

Non-inferiority trial 18,113 patients randomized

110 or 150 mg dabigatran – blinded Adjusted dose warfarin – unblinded

2.0 year median follow-up Primary outcome: stroke or systemic

embolizationConnolly SJ, et al. N Engl J Med 2009; 361:1139-1151.

RE-LYCumulative Hazard Rates for the Primary Outcome of Stroke or Systemic

Embolism According to Treatment Group.

Connolly SJ et al. N Engl J Med 2009;361:1139-1151.

A Few Words About AF Ablation

Increasingly effective procedure, depending on type of AF

Paroxysmal > Persistent > Permanent Failure of drug therapy or importance of

maintaining SR for hemodynamic purposes

Not without risk – requires experience

Thank You!

Questions??