treatment of atrial fibrillation in 2009 - ucsf cme · treatment of atrial fibrillation in 2009 ......

Treatment of Treatment of AtrialAtrialFibrillation in 2009Fibrillation in 2009

Gregory Marcus, MDAssistant Professor of Medicine

Division of Cardiology, Electrophysiology SectionUniversity of California, San Francisco

No potential conflicts of interest to disclose

Epidemiology

• AF is the most common sustained arrhythmia in adults

• It affects at least 2.3 million Americans– Expected to affect > 4 million by 2030

• Affects ~4% of everyone over age 60 and ~10% of everyone over age 80

• The age-adjusted incidence is increasing1

1. Miyasaka Y. Circulation 2006;114:119-125

Epidemiology…so what?• AF is the most common cause of

embolic stroke1

• Rate of stroke in AF patients is 4.5%/ year1

• 15% of all strokes in the US can be attributed to AF2

• AF is associated with an increase in mortality, from 1.3-2 times3

1. Singer. Chest 2004;126:429-4562. Nattel. Lancet 2006;367:262-2723. Page. N Engl J Med 2004;351:2408-16

Case

• A 58 yo man presents with fatigue and dyspnea on exertion

• PMH: HTN• Meds: Lisinopril 10 mg daily• PE: HR 123, BP 135/80

Irregularly irregular rhythm, variable intensity of S1

The Best Next Step is…

1 = Send to the emergency department

2 = Manage as an outpatient

Questions

• What work-up does he need?• Does he need to be anticoagulated?

When?• Should he be cardioverted or rate

controlled? How?• When should ablation be considered?

What work-up does he need?

PI RAT E S


P ulmonary/ pulmonary embolismI schemiaR heumatic heart diseaseA trial myxomaT hyrotoxicosisE thanolS epsis

1. Complete history and physical examination


P ulmonary/ pulmonary embolismI schemiaR heumatic heart diseaseA trial myxomaT hyrotoxicosisE thanolS epsis



R heumatic heart diseaseA trial myxomaT hyrotoxicosis


2. Transthoracic Echocardiogram


A trial myxomaT hyrotoxicosis



What work-up does he need?1. Complete history and physical examination


-- Left ventricular hypertrophy

-- Hypertrophic obstructive cardiomyopathy

-- occult valvular disease

-- occult pericardial disease


T hyrotoxicosis



3. Routine labs and thyroid function tests


1. ACC/ AHA Guidelines for Management of Patients with AtrialFibrillation. J Am Coll Cardiol 2006;48:e149-246

2. N Engl J Med 2004;351:2408-16 (they add CXR)



3. Routine labs and thyroid function tests

*

*

The Best Next Step is…

1 = Rate control and allow atrial fibrillation to continue

2 = Make efforts to achieve and maintain sinus rhythm

3 = 1 and 2 are equal

Rate or Rhythm Control?

• Sinus is better than atrial fibrillation, right?

• Means to maintain sinus rhythm are suboptimal

• Randomized trials


Inclusion:• ≥ 65 years old with a risk factor for stroke or death

– Of 4070 enrolled, 71% HTN, 26% CAD, 23%CHFIntervention:• Randomized to rate control with anticoagulation versus rhythm

control with cadioversion and antiarrhythmic drugs– Warfarin therapy could be stopped at the discretion of the prescribing

physician after sinus rhythm had been maintained in the rhythm control group for 4 and preferably 12 weeks

Outcomes:• Primary: No overall difference in mortality, trend towards

increased mortality in the rhythm control group • No overall difference in quality of life• No overall difference in stroke


STAF (n=200)- no difference in composite endpoint of death and thromboembolic events

PIAF (n=252)- No difference in symptomatic improvement

HOT CAFÉ (n=205)- No difference in composite death, thromboembolic events, hemorrhage


Inclusion:• ≥ 65 years old with a risk factor for stroke or death

– Of 4070 enrolled, 71% HTN, 26% CAD, 23%CHFIntervention:• Randomized to rate control with anticoagulation versus rhythm

control with cadioversion and antiarrhythmic drugs– Warfarin therapy could be stopped at the discretion of the prescribing

physician after sinus rhythm had been maintained in the rhythm control group for 4 and preferably 12 weeks



-- Antiarrhythmic agents can be proarrhythmic-- Efficacy is poor: 23-63% in NSR in rhythm control group in these trials-- Reanalysis of on-treatment outcomes in AFFIRM showed that the presence of sinus rhythm was associated with a 47% reduction in mortality (p<0.0001)1

1. Circulation 2004;109:1509-13





-- Symptomatic patients unlikely to be enrolled-- Symptoms despite rate control are an appropriate reason to consider cardioversion



-- Strokes occurred in patients off warfarin or with subtherapeutic INR (< 2.0)

-- AF is often asymptomatic! Even in patients with symptomatic AF!1

1. Circulation 1994;89:224-7.

A clear lesson from these trials:

**A rhythm control strategy does not negate the need for warfarin therapy**

… assuming warfarin is indicated

Anticoagulation in AFWho needs it?

• Warfarin is the most effective available therapy to prevent stroke in patients with AF– 5 RCT of vit K antagonists v. placebo highly

significant risk reduction in stroke of 62% (95% CI 48% to 72%)1

– Strokes on warfarin are significantly less severe2

– Warfarin reduced overall mortality in AF patients2

1. Ann Intern Med 1999;131:492-501

2. Chest 2004;126:429S-456S)

3. Eur Heart J 2005;7:C12-18


• Warfarin is not perfect– Significantly increase major bleeding (0.9%

to 2.2%) and intracerebral hemorrhage (0.2% to 0.4%)1

– Most efficacy with INR> 2, least bleeding with INR <32

1. Eur Heart J 2005;7:C12-18

2. Chest 2004;126:429S-456S


• Aspirin has some efficacy versus placebo, but inferior to warfarin1

– Less bleeding risk

1. Chest 2004;126:429S-456S

The Best Next Step is..

1 = No anticoagulation

2 = Aspirin

3 = Warfarin

4 = Aspirin or Warfarin


CHADS 2 score:11 point for:

CHF (or reduced systolic function), HTN, age ≥ 75 years, DM

2 points for:History of stroke or TIA

0-1: low risk2-3: moderate risk4-6: high risk

1. JAMA 2001;285:2864-2870

Anticoagulation- who needs it?

• Class I: If more than one risk factor warfarin

• Class IIa: If just one risk factor, depending on assessment of bleeding risk, ability to safely administrate, and patient preference aspirin (81-325 mg) or warfarin

• Class IIa: If one or more “less well established” risk factors: age 66-74, female gender, or CAD aspirin or warfarin

Anticoagulation- extra tid-bit

• Class IIa: If no mechanical valve, can interrupt anticoagulation for up to 1 week without substituting heparin for procedures, etc.


Wait, wait, wait…so what about my 90 year old frail patient?

• Although the risk of warfarin related bleeding increases primarily with anticoagulation intensity and age, the greater risk of stroke in the elderly outweighs the risk of bleeding.1

• One analysis of bleeding risk in the elderly suggested no important role of factors such as a history of falls, presumed age-related incompetence in the control of anticoagulation, or a history of stroke2

-- Non-compliance with INR monitoring, bleeding diasthesis, and poorly controlled HTN (>160/90) were risk factors

1. Lancet 2006;367:262-72

2. Arch Intern Med 2003;163:1580-86

Anticoagulation- extra tid-bits

• Class III: Long-term vitamin K antagonists are not recommended for primary prevention of stroke in patients younger than 60 without heart disease

Unless…

I decide to go with

• Most thrombi in atrial fibrillation arise from the left atrialappendage

• Cardioversion can reduce left atrial appendage function

-- Even from AF to sinus

• The pericardioversion period is a particularly pro-thrombotic time

-- Regardless of mode: DC/ electrical, pharmacologic, spontaneous

I decide to go with

• Prior to cardioversion:1, 2

-- Can exclude preexisitngthrombus by TEE

-- Can anticoagulate (therapeutic/ INR 2-3) for at least 3 weeks prior to cardioversion

1. JACC 2006;48:e149-246

2. Chest 2004;126:429S-456

I decide to go with

• During and after cardioversion:1, 2

-- Anticoagulation for at least 4 weeks

-- Applies even to those who would otherwise not require anticoagulation

• The magic 48 hours

-- Must be documented!1. JACC 2006;48:e149-246

2. Chest 2004;126:429S-456

I decide to go with Rate Control

• Beta-blockers and nondihydropyridine calcium channel blockers are first line1

-- Metoprolol, atenolol, propanolol, even carvedilol2

-- diltiazem or verapamil

• Digoxin is second line because heart rates often increase with exercise

-- Combination with another AV nodal blocking agent can be very effective3

1. JACC 2006;48:e149-246

2. Eur J Heart Fail 2001;3:437-40

3. JACC 1999;33:304-10

Ablation

• High success (> 90-95%) and low risk (< 1%): – AV nodal ablation and pacemaker– Atrial flutter ablation– SVT ablation

Ablation

• Lower success (60-90%) and higher risk (4-6%):1-5

– Atrial fibrillation ablation

1. Circulation 2003;108:2355-602. JACC 2003;42:185-1973. JACC 2004;43:2044-534. JAMA 2005;293:2634-405. N Engl J 2006; 354: 934-41

Ablation

Ablation

• Lower success (60-90%) and higher risk (4-6%):– Atrial fibrillation ablation

• Recommended for symptoms only– More effective for paroxysmal than chronic– Generally should have failed 1-2

antiarrhythmic medicines

Ablation?

Rhythm Control StrategyApproach to Current Therapy

Rhythm Control StrategyApproach to Current Therapy

1. Can use as “pill in the pocket”1

2. Need AV nodal blockers as well

1. N Engl J Med 2004;351:2384-91.

Dronaderone = MultaqEfficacy < Amiodarone NYHA

Class I-II

NYHA Class III-IV

Dronaderone = Multaq

• Probably safe (unless there is severe heart failure)

• Not clear that efficacy is any better than other agents

• Nice to have another choice

• Increases creatinine apparently without decreasing GFR

1: J Am Coll Cardiol. 2009 Sep 15;54(12):1089-95. 2. N Engl J Med. 2008 Jun 19;358(25):2678-87. 3. N Engl J Med. 2009 Feb 12;360(7):668-78. 4. N Engl J Med. 2007 Sep 6;357(10):987-99.

The future?

The future?• AF may be caused by inflammation and/

or fibrosis in the atrium• Therapies aimed at the atrial substrate

– Some data for statins– Some data for ACE inhibitors and ARBs

• Anticoagulants that are not warfarin– Oral thrombin inhibitors (ie, Dabigatran)– Atrial appendage occluder

• Atrial specific ion channel blockers

The future?• Ablation

– Constantly evolving– Mapping systems– Navigation systems

A. B.

D.C.

Thank You

treatment of atrial fibrillation in 2009 - ucsf cme · treatment of atrial fibrillation in 2009 ......

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