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Dr. Mario Fitz MauriceElectrofisiología Cardíaca Hospital Rivadavia

mdfitzmaurice@gmail.com

AFAC

Anticoagulation in Atrial Fibrillation

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65.084 con ≥ 70 años y FA

813.546 con 70 años o más

Población: 40.677.348 (Julio 2008 estimado)

Prevalence of AF increases with age

Population: 40,677,348 (estimation July 2008)

813,546 with 70 years of age or more

65,084 with > 70 years of age and AF

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THE EPIDEMIC

Due to the aging of population, this figure is expected to duplicate in 30 years.. Go AS, et al. JAMA 2001;285:2370-2375.

In 2007, AF was diagnosed in 6.3 million people from USA

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AF increases the risk of stroke

AF relates with prothrombotic states1

Risk ~5 times greater for stroke1

In USA one stroke occurs per minute

A cardioembolic stroke is associated to a 25% mortality at 30 days4

Stroke related to AF has a ~50% mortality after 1 year5

Up to 3 million people suffer stroke associated to AF each year all over the world1-3

Effect of 1st ischemic stroke in patients with AF

Disabling

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Evidence in anticoagulation

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• SPAFSPAF11 SStroke troke PPrevention in revention in AAtrial trial FFibrillationibrillation

• BAATAFBAATAF22 BBoston oston AArea rea AAnticoagulation nticoagulation TTrial for rial for AAtrial trial FFibrillationibrillation

• CAFACAFA33 CCanadian anadian AAtrial trial FFibrillation ibrillation AAnticoagulationnticoagulation

• AFASAKAFASAK44 Copenhagen InvestigatorsCopenhagen Investigators

• SPINAFSPINAF55 SStroke troke PPrevention in revention in NNonrheumatic onrheumatic AAtrial trial FFibrillationibrillation

Clinical studies on Clinical studies on AFAF

1 Circulation. 1991;84:527-539.2 N Engl J Med. 1990;323:1505-15113 J Am Coll Cardiol. 1991;18:349-355

4 The Lancet. 1989;1:175-1785 N Eng J Med. 1992;327:1406-1412

AFASAK SPAF IIISPINAFBAATAF SPAF IISPAF I BAFTAACTIVE

WEAFT SPORTIF

AC vs P

LACEBO

SAFETY IN

ELDERLY

PEOPLE

INR

RANGE

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67% of general reduction of stroke

Stroke Death

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SPAF Investigators. Lancet. 1996;348:633-638.

Terapia combinada mejor

Dosis-ajustada warfarina mejor

Stroke, IAM o muerte

vascular

Evento primario o

muerte vascular

Todos stroke incap

Stroke isquémico

incapacitante

Evento primario

0 0.5 1 1.5 2

Riesgo Relativo e IC 95% (barra horizontal)

Hemorragia mayor

Events: Relative risk, adjusted dose vs combination therapy

SPAF III

Adjusted dose

Warfarin better

Combination therapy

Better

Primary event

Disabling ischemic stroke

All disabling strokes

Primary event or vascular death

Stroke, AMI, or CV death

Mejor bleeding

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Duda en ancianos

BAFTA Mant J. Lancet 2007;370:493-503.

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Anticoagulation in people older than 75 years old BAFTA – Birmingham Atrial Fibrillation Treatment of the Aged

Patients with AF ≥ 75 years old (median 81,5 ± 4,2 years) Randomization 1:1 Warfarin (INR 2-3) versus Aspirin 75 mg/day F/U: 2.7 years

EP 1°: Disabling stroke or arterial embolism

Major bleedingExtracranial major bleeding

RR:0.48 (0.28-0.80) p=0.003

NNT:50

nsns

Events per year (%)

Warfarin (n=488) Aspirin (n=485)

n=973

RRR>50%

P=0.002

All strokes

1 Mant J. Lancet 2007;370:493-503.

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So, ¿Why a new therapeutic armory?

Unpredictable response

Narrow therapeutic window

(INR 2-3)

Systematic monitoring of coagulation

Slow start and disappearance of

effect

Frequent dose adjustment

Numerous

interactions with food

Numerous interactions

with other drugs

Resistance to warfarin

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Sites of action, new anticoagulants

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Nuevas DrogasEn fa

Dabigatran

Apixaban

Rivaroxaban

Clopidogrel

EdoxabanIn patients with AC

contraindicated

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In the presence of contraindications for AC

With severe adverse effects of hepatotoxicity

NNT=26.3 RR 64%

Warfarin not blind, GI Bleeding, AMI, two doses, costs, most CHADS 1

NNT=178

RR 36%

Meta-analysis of ischemic stroke or systemic embolism

Category

W vs placebo

W vs W in low doses

W vs ASA

W vs ASA + clopidogrel

W vs ximelagatran

W vs dabigatran 150

In favor of warfarin In favor of another treatment

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Dabigatran

WarfarinAcenocumar

ol

Evidence/Years of use

Cost/Benefit/Evidence

Warfarin

Direct inhibitors

$$

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AFASAK SPAF IIISPINAFSPAF IISPAF I BAFTAEAFT SPORTIF

But while the race continues...

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Waldo AL. J Am Coll Cardiol 2005;46:1729-1736.

AC in the real worldUnderuse of AC regardless of risk

No treatment

ASA

Warfarin + ASA

Warfarin

All Low risk

Moderate risk

High risk

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ACO: Chronic anticoagulationACO: Chronic anticoagulation

n = 407 (48,5%)

n = 288 (34,3%)

n = 152 (18,1%)

n = 135 (16,1%)

N = 840N = 840

Labadet C y col. Reg RAC 2000

AC, Real worldTreatments used to prevent thromboembolism

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Average= 50% without AC

Management of AF in clinical practice:

Indication of K vitamin antagonistsNo anticoagulation

K vitamin antagonists

Medicare cohort, USA

ATRIA cohort (managed care system, California, USA)

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13 Community Hospitals

21 Academic Hospitals

Nearly half of patients with AF and high risk received anticoagulation therapy

Waldo et al. JACC 2005; 46(9): 1729-1736

AC: Real worldUnderused in AF

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Stroke reduction>80%

Stroke reduction67%

INR control:

Clinical studies vs clinical practice

INR control in clinical studies vs clinical practice (TTR*)

*TTR = Time in Therapeutic Range (INR 2.0-3.0)

Clinical study1

Clinical practice2

% o

f p

ati

en

ts e

lig

ible

th

at

rece

ive w

arf

ari

n

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AGE YEARS

69 - 79 80 - 89 > 89

70 - 79 80 - 8960 - 69

Patients w/o AC

STROKES PER 1000 PTS/YEAR

The risk of stroke is increased dramatically

with age

Use of ACHowever the use of

AC IS DECREASING

In summary...

100

80

60

40

20

0

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Cohort in community, Olmsted County, Minnesota n=270

PSAF: Persistent AFPXAF: Paroxysmal AFPAF: Permanent AF

Keating RJ. Am J Cardiol 2005;96:1420 –1424.

Cohort in community, Stockholm n=2824

Paroxysmal AF Prognostic impact

DEATH

Friberg L. Eur Heart J 2007;28:2346-2353.

PSAF: Persistent AFPXAF: Paroxysmal AFPAF: Permanent AF

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Paroxysmal AFPrognostic impact

DEATH

Mortality according to CHADS Rate of standardized mortality (“how higher is risk than the general population”)

Friberg L. Eur Heart J 2007;28:2346-2353.

Cause of death RMS 95% CI

Cardiovascular 2.1 1.6 – 2.6

Myocardial infarction 2.4 1.4 – 3.7

Ischemic disease 2.6 1.7 – 3.4

Heart failure 2.6 1.3 – 5.2

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Paroxysmal AFPrognostic impact

Stroke

Incidence of strokeEvents/1000 patients/year

Paroxysmal AF Permanent AFNo details

1 Friberg L. Eur Heart J 2009;doi:10.1093. 2 Wang TJ. JAMA 2003;290:1049-1056. 3 Hart RG. J Am Coll Cardiol 2000;35:183-187.

RMS 95% CI

Ischemic stroke 2.12 1.5 – 2.7

≤ 75 y.o. 2.27 1.3 – 3.8

75 y.o. 2.05 1.3 – 2.8

Men 1.98 1.1 – 2.8

Women 2.24 1.4 – 3.1

Rate of standardized ischemic stroke incidence

26 (2) Friberg L. Eur Heart J 2009;doi:10.1093.

(1) Waldo AL. J Am Coll Cardiol 2005;46:1729-1736.

P0.001

% of AC

FAPXFAPX

AC in the real world

The risk of stroke is the same in patients with AF, without taking into account whether AF is paroxysmal or sustained

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NOT TO LOSE THE RACE

AFAC

CHA2DS2VAScAntecedentes de Stroke 2Edad > 75 años 2HTA 1DBT 1Insuficiencia Cardíaca 1Antec, Vascular 1Edad >65<75 1Sexo femenino 1

Alto Riesgo >4Moderado Riesgo 2-3Bajo Riesgo 0-1

History of stroke

Age >75 y.o.

HTN

Diabetes

Heart failure

History of CV disease

Age >65<75

Female gender

High risk >4

Moderate risk 2-3

Low risk 0-1

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AF

Dr. Mario Fitz Maurice

THANK YOU VERY MUCH FOR YOUR ATTENTION

Rhythm control

Rate control,

but without forgetting

INR CONTROL