1 Dr. Mario Fitz Maurice Electrofisiología Cardíaca Hospital Rivadavia mdfitzmaurice@gmail.com AF AC Anticoagulation in Atrial Fibrillation.
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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
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
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