Fibrillazione atriale e rischio di stroke nell`anziano

Fibrillazione atriale e
rischio di stroke
nell’anziano
Niccolò Marchionni
Cattedra di Geriatria, Università di Firenze
SOD Cardiologia e Medicina Geriatrica
AOU Careggi , Firenze
Società Italiana di Gerontologia e Geriatria
Incidenza
(per 1000 anni‐persona)
Incidenza di FA per età
60
40
20
0
30
40
Miyasaka Y. Circulation, 2006
50
60 70
Età (anni)
80
90
100
Schnabel RB et al, Lancet 2009
Age (years)
BMI (Kg/m2)
SBP (mmHg)
45-49
-3 – 1
<160
0
50-54
-2 – 2
160 – 199
1
55-59
0–3
>200
2
60-64
1–4
45-54
5
65-69
3–5
55-64
4
70-74
4–6
65-74
2
75-79
6–7
75-84
1
80-84
7–7
>85
0
>85
8–8
45-54
10
<30
0
55-64
6
>30
1
65-74
2
>75-84
0
No
0
Yes
1
<160
0
>160
1
PR (ms)
Age / Cardiac
murmur
Age / HF
Tx Hypertension
Women / Men; Age / Cardiac murmur: Age at which significant cardiac murmur developed; Age / HF: Age of heart failure
Predicted 10‐year risk of atrial fibrillation
10‐year risk (%)
30
>30
Participants – N = 4764; Women:
55% Age: 45‐95 years
A Fib (10 years): N= 457 (10%)
20
22
16
12
10
8
6
<1
2
2
3
1
2
3
4
4
5
6
Risk Score
0
0
Schnabel RB et al, Lancet 2009
7
8
9
>10
Atrial Fibrillation and
Cardioembolic syndromes
Cerebral Cardio‐embolism (85%)*
Peripheral Cardio‐embolism (15%) *
‐ Coronary (MI)
‐ Visceral (Mesenteric, Renal, etc.)
‐ Limbs
* Cabin Am J Cardiol 1990
Cerebrovascular Disease: Stroke Subtype
Hemorrhagic stroke (17%)
Intracerebral
hemorrhage (59%)
Ischemic stroke (83%)
Lacunar small vessel disease (25%)
Atherothrombotic
disease (20‐25%)
SAH (41%)
Embolism
(20%)
Cryptogenic (30%)
Albers GW et al. Chest. 1998;114:683S‐698S.
Rosamond WD et al. Stroke. 1999;30:736‐743.
CE/AF Stroke rate (N/100.000/year)
227
216
240
Men
Women
200
160
120
108
73
80
40
0
28
0 0
0 1
4 2
12
<40 40-50 50-60 60-70 70-80 >80
Age (years)
CE/AF stroke = 572/3064 (18.7%)
Bejot Y, 2009
CE/AF 80.6 vs. other strokes 73.6 years
AF monitoring after cryptogenetic stroke
Pts. with AF detected (%)
30
25
20
17,5
15
11,8
10
5
6,8
2,7
0
1 ECG
Multiple
ECGs
D. Jabaudon. Stroke 2004; 35: 1647‐1651
24 h Holter
7 d Holter
Intermittent AF may account for a large proportion of otherwise cryptogenic stroke
A study of 30‐day cardiac event monitor
Conclusion:
The 30‐DEM changed the medical treatment of 20% of patients with otherwise cryptogenic stroke because of the detection of intermittent AF despite no detection of AF on electrocardiography and in telemetry monitoring in the majority of patients. Elijovich et al. J of Stroke and Cerebrovascular Diseases 2009
Clinical state at time of maximum impairment among patients with and
without AF in a European Concerted Action
18.0%
(7 Countries, first stroke, age: 72 years, N=4462)
Atrial Fibrillation
Yes
(N=803)
No
(N=3659)
P
Confusion
39.0
27.6
<0.001
Coma
12.3
7.6
<0.001
Paralysis
51.4
36.6
<0.001
Aphasia
41.8
30.3
<0.001
Disarthria
35.0
33.2
NS
Swallowing problems
40.3
23.6
<0.001
Urinary incontinence
54.6
38.7
<0.001
(%)
Lamassa M, 2001
Lamassa M, 2001
AF – Age: 77** yrs, Women: 58%**
p<0.0001
32,8
Mortality (%)
30
20
19,9
19
10
80
p<0.0001
12,7
0
Destination at discharge (%)
40
No AF – Age: 71 yrs, Women: 48%
p<0.0001
3-Month
P=NS
71
60
61
40
20
9
0
In-Hospital
P=0.003
6
10 9
Home Institution Rehab Tx
**: p<0.001 vs the same category of No AF pts
No AF
(N=1992)
AF
(N=470)
Total anterior
circulation Lacunar
infarct**
infarct
Lacunar
infarct**
16
Posterior
circulation
infarct
33.8
Total anterior
circulation
infarct
29.2
25.1
15.5
34.7
Partial anterior
circulation infarct*
Posterior
circulation
infarct
17
*: p<0.05 vs the same category of No AF pts
**: p<0.001 vs the same category of No AF pts
28.7
Partial anterior
circulation infarct
Lamassa M, 2001
Rischio di recidive a due anni, per tipo di ictus (n= 531)
Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long‐term survival in ischemic stroke subtypes: a population‐based study. PL Kolominsky‐Rabas et al. Stroke. 2001;32:2735‐2740 Validation of clinical classification schemes for predicting stroke
Results from the National Registry of Atrial Fibrillation
CHADS2 Risk Stratification Scheme
Risk Factors
C ‐
H ‐
A ‐
D ‐
S2 ‐
recent Congestive heart failure
Hypertension
Age >75 years
Diabetes mellitus
History of Stroke or TIA
Gage, JAMA, 2001
Rockson, JACC, 2004
Score
1
1
1
1
2
Relationship between CHADS2 Score and Risk of Stroke
Results from the National Registry of Atrial Fibrillation
Annual Stroke Rate (%)
20
Elevato 18.2
15
12.5
Medio
10
5
0
Gage, JAMA, 2001
Rockson, JACC, 2004
Basso
2.8
1.9
0
1
4.0
8.5
5.9
2
3
4
CHADS2 Score
5
6
Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk
Factor‐Based Approach
The Euro Heart Survey on Atrial Fibrillation
Lip, Chest, 2010
Stroke Risk Assessment in AF: the CHA2DS2‐VASc Score
Stroke Risk Factor
Congestive Heart Failure / LV Dysfunction
Hypertension
Age >75 years
Diabetes mellitus
Stroke / TIA / TE
Vascular Disease (MI, PAD, aortic plaque)
Age 65-74 years
Sex category (female)
Score
1
1
2
1
2
1
1
1
Maximum score = 9; Score >1 – OAC; Score = 1 – ASA (75‐325 mg) or OAC (preferred); Score = 0 ‐ ASA (75‐325 mg) or None (preferred) Thromboembolism Rate
(per 100 person‐years)
Go AS et al. Circulation 2009
Study period:
July 1996 – December 1997
through September 30, 2003
Events
N = 676 / 10,908
4.22
2.76
1.63
≥60
N=7,690
72 yrs
45‐59
N=2,499
76 yrs
<45
N=1,338
78 yrs
Estimated Glomerular Filtration Rate (mL/min/1.73 m2)
GFR =186•[serum creatinine (mg/dL)]‐1.154•(age)‐0.203•(0.742 if female)
Rischio annuale di ictus in pazienti con
fibrillazione atriale, per gruppi di età
The Atrial Fibrillation Investigators
Rischio relativo annuale
Gruppi di età (anni)
10
<65
65 - 75
>75
8.1
8
6
AFI, Arch Int Med, 1994
Rockson, JACC, 2004
Fattori di rischio:
diabete,
ipertensione,
storia di ictus/TIA
5.7
4.9
4.3
4
2
3.5
1.7
1 1
1.1
1.7
1.7
1.2
0
No
Si
No
Si
No
Fattori di rischio
Si
Placebo
Warfarin
Probabilità di sopravvivenza
Analisi di Kaplan‐Meier sulla sopravvivenza a 30 giorni dopo ictus ischemico in 596 pazienti con fibrillazione atriale
Age by treatment
None – 79 years
Aspirin – 80 years
Warfarin – 76 years
Giorni
2003;349:1019‐1026
A novel user‐friendly score (HAS‐BLED) to assess one‐year risk of major bleeding in atrial fibrillation patients: the Euro Heart Survey
Pisters, Chest, 2010
Bleeding Risk Assessment in AF: HAS‐BLED Bleeding Risk Score
Letter
Clinical Characteristic
Points
H
Hypertension
1
A
Abnormal Renal / Liver Function
1
S
Stroke
2
B
Bleeding
1
L
Labile INRs
2
E
Elderly
1
D
Drugs / Alcohol
1
Maximum score = 9; Hypertension – Sap >160 mmHg; Drugs – antiplatelets agents or NSAIDS
Score > 3 – High risk patient: Caution and regular review following the initiation of antithrombotic therapy (OAC & ASA)
Incidenza emorragie maggiori
(eventi per 100 anni‐persona)
13.08
10
Età ≥ 80 anni
N=153
8
P=0.009
6
4.75
4
Età < 80 anni
2
N=319
0
0
100
200
300
Durata terapia con warfarin (giorni)
Circulation, 2007
N=472
Età=77 (65‐97)
400
VKA: stretto range terapeutico
Target
INR
(2.0-3.0)
80
Eventi / 1000 pazienti anno
Ictus ischemico
Emorragia intracranica
60
40
20
0
<1.5
1.5–1.9
2.0–2.5
1. Hylek EM, et al. N Eng J Med 2003; 349:1019-1026.
2.6–3.0
3.1–3.5
3.6-4.0
4.1-4.5
>4.5
International Normalised Ratio (INR)
Incidenza emorragie maggiori
(eventi per 100 anni‐persona)
99,3
100
80
IRR ≤90 vs. >90 = 3.31
IRR ≥4 vs. <4 = 19.34
60
40
20
15,8
4,1
0
<2
14,2
4,1
3,8
2‐3 3.1‐ <4
Valori di INR
≥4
Circulation, 2007
≤90
>90
Inizio terapia (giorni)
Vascular Event
Ischemic Stroke
Annual rate (%/year)
20
Control (Ref.) – 1
Antipl. Ther. (HR) – 0.81
OAC (HR) – 0.36
10
0
<65
Serious Hemorrhage
65‐70 70‐75 75‐80
20
Trials – N=12; Patients – N=8932
Control – N=1971
Antiplatelet therapy – N=3531
Oral anticoagulation– N=3430
10
0
<65
65‐70 70‐75 75‐80
>80
Van Walraven, Stroke, 2009
>80
The Net Clinical Benefit of Warfarin Anticoagulation in Atrial Fibrillation
Daniel E. Singer, MD, Yuchiao Chang, PhD, Margaret C. Fang, MD, MPH, Leila H. Borowsky, MPH, Niela K. Pomernacki, RD, Natalia Udaltsova, PhD, and Alan S. Go, MD
Massachusetts General Hospital, Boston, Massachussetts, and University of California, San
Francisco, San Francisco, and Kaiser Permanente of Northern California, Oakland, California.
The ATRIA Cohort of AF pts
N = 13559; Age: 73 years
Annual Rate
Ictus/Embolism ‐ Warfarinoff: 2.10% vs. Warfarinon: 1.27%
ICH ‐ Warfarinoff: 0.32% vs. Warfarinon: 0.58%
Net Clinical Benefit :
(annual rate of ischemic strokes / systemic emboli prevented by warfarin) minus (intracranial hemorrhages due to warfarin) * impact weight
The impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism
Ann Intern Med, 2009
Le raccomandazioni dell’American Geriatrics Society
sul monitoraggio della terapia anticoagulante nell’anziano
Dosaggio dei valori di INR:
1.
Quotidiano fino al raggiungimento di valori stabili
2.
Due ‐ tre volte a settimana per i successivi 7‐15 giorni
3.
Una volta a settimana nel mese successivo
4.
Quindi, una volta al mese American Geriatrics Society Clinical Practice Committee
J Am Geriatr Soc 2002
Conclusions
1. Physicians may be apprehensive about prescribing OAC to elderly patients, given concerns about a higher risk of hemorrhage.
2. However, age alone should not prevent prescription of OAC in elderly patients, given the potential greater net clinical benefit among such patients.
3. Appropriate stroke and bleeding risk stratification and choice of antithrombotic therapy are essential.
4. Once OAC is initiated, good INR control (at least 65% TTR) and the provision of a health care infrastructure to support such INR therapeutic targets are crucial to prevent warfarin‐associated complications.
JACC, 2010