La malattia cardiovascolare nell’anziano: strategie di ... · Female UHF post-PCI UA MI 75...
Transcript of La malattia cardiovascolare nell’anziano: strategie di ... · Female UHF post-PCI UA MI 75...
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Strategie di Prevenzione del Rischio CCV GlobaleBergamo 13 Novembre 2010
Giuseppe Musumeci
USC Cardiologia Ospedali Riuniti di Bergamo
La malattia cardiovascolare nell’anziano: strategie di prevenzione e trattamento
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Changes in global population from 2000 to 2030Percent Aged 65 and Over
US Census Bureau 2000
2000
2030
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Incremento della popolazione anziana in Italia
Fonte ISTAT
81%
15% 4%
72%
19%
9%
64%15%
21%
2001 2025 2050
< 65 anni
> 65 anni
> 80 anni
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0
10
20
30
40
50
60
70
Ipertensione arteriosa Artrosi-artriti CardiopatieM. gastrointestinali Diabete CancroBPCO Depressione Incontinenza
57.2
50.344.5
29.124 24
21 18.516.4
12
Incidenza (n. per 100 persone) di malattie croniche nell’anziano
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Cardiopatie: prima causa di morte e ricovero nell’anziano
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Normal aging changes in the cardiovascular system
� Increased arterial stiffnessand aortic impedance
� Increased cardiac stiffness.
� LV and myocyte hypertrophy. Loss of myocyte.
� Normal systolic function at rest. Reduced
functional reserve (HR and LVEF) during stress.
� Reduced baroreceptor sensitivity.
Lakatta EG , Circulation 1993;87:631-6.
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Prevalence of Coronary Heart Disease by Age and Sex in the U.S. from 1988-94
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
20%
25-44 45-54 55-64 65-74 75+
Male Female
Age, years
Per
cent
of
Pop
ulat
ion
Source: National Health and Nutrition Examination Survey
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0%
5%
10%
15%
20%
25%
30%
35%
0-19 20-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90+
male female
HF: Prevalence and annual mortality by age
letalità
Prevalence 1.2% (0.02%-18.2%)Incidence 3.2/1000 (0.1-49/1000)
Annual mortality 16% (3.6%-31%)
age
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Patient over 65 years (US)
10
30
50
70
90
1950 2000 2050‘60 ‘70 ‘80 ‘90 ‘10 ‘20 ‘30 ‘40
80.1millions
12.3millions
In m
illio
ns
P. Lee JAMA2001; 286: 708
More Women, Elderly seeking treatment for AMIMore Women, Elderly seeking treatment for AMI
Hospitalized AMI Patient
24 % 37 %
43 %
≥ 75
1975 1995
35 %Women
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RCTs of early invasive treatment in NSTEACS
Trial Average age % pts >75y Outcome
TIMI IIIB 59 3 Benefit only >65 y
VANQWISH 61 8 No difference
FRISC II 65 Excluded Benefit only >65 y
RITA 3 63 No age classes reported
Not reported by age
TACTICS 62 12.5 39% RR >65
56% RR >75
ICTUS 61 Not reported Trend towards > benefit >65y
…but not in trials
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CADILLAC Trial30 Day Outcomes Stratified by Age
< 55 yrs 55-64 yrs 65-74 yrs ≥ 75 yrs
0,8
1,7
0
1,2
3,6
0,2
3,64,1
0,2
4,8
6,7
0,4
0
2
4
6
8
10
Death Bleeding Stroke
%
p < .0001
p = 0.02
Guagliumi G, Musumeci G. et al Circulation 2004; 110: 1598
p < .005
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CADILLAC : Elderly Patients (≥ 75 years) treated with primary PCI
1 year free from death
100
95
9085
8075706560
100 150 200 250 300 250 400500
Time in Days
Per
cent
Sur
vivi
ng98 %98 %93 %88 %
G . Guagliumi, G. Musumeci et al. Circulation 2004
Age < 55Age < 55
55 ≤ age < 6555 ≤ age < 6565 ≤ age < 7565 ≤ age < 75Age ≥75Age ≥75
%
Log-Rank p = .0001
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0
5
10
15
20
25
30
35
40
<65 65-74 75-84 85+
Stroke Renal Insuff CHF
Age and Comorbid Illness%
of p
opul
atio
n
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Rischio nei pazienti con sindrome coronarica acutaRelazione con l’età
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Sindrome metabolica: prevalenza in relazione all’etàP
rev a
len
ce, %
Age, yrAdapted from: Ford ES, et al. JAMA. 2002;287:356-359.
47 million or 23% of US Adults Have Metabolic Syndrome
0
5
10
15
20
25
30
35
40
45
20-29 30-39 40-49 50-59 60-69 ?70
Men (n=4265)
Women (n=4559)
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Lake Saints Hospital Study
0
5
10
15
20
25
30
35
<50 50-59 60-69 70-79 >80
No statine Statine
Classi d’età
N. P
azie
nti c
on r
ecid
iva
di e
vent
i car
diov
asco
lari
P=0.35P=0.04
P=0.04
P=0.01
P=0.004
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Dislipidemici trattati con statine nelle varie classi d’etàStudio FADOI 3
0
5
10
15
20
25
30
35
35 - 44 45 - 54 55 - 64 65 - 74 75 - 84 > 85
% receiving statins
etàFADOI 3,2002
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Medical Treatment vs Coronary Revascularization in the Elderly: The TIME study
MED
0 1 2 3 4 5 6
INV
Log Rank p=<0.0001
Time scince randomization (years)
Pro
port
ion
with
out M
AC
E
0
2
4
6
8
10
Extracted from Pfisterer M. Circulation 2004;110:1213-1218
INV
MED
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Cardiac Surgery in the Elderly
0
10
20
30
<65 years 65 - 74 >74 years
30-day mortality
Major complications
Jarvinen et al, World J Surg 2003
RISK
AGE (per 5 years) OR 1.2; 95%CI 0.9-1.6
Renal failure OR 1.4; 95%CI 0.9-2.1
History of CHF OR 1.4; 95%CI 1.0-1.9
COPD OR 1.7; 95%CI 1.2-2.3
Vascular disease OR 1.5; 95%CI 1.2-1.9
Emergency OR 3.6; 95%CI 2.8-4.8
*Alexander et al, JACC, 35:731-8
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PCI vs. CABG in Elderly Patients: the BARI Trial
0
1
2
3
4
5
6
<65 years >65 years <65 years >65 years <65 years >65 ye ars
Rat
e (%
)CABG
Stent
Death Q-wave-MI Stroke
Mullany et al, Ann Thorac Surg 1999
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STEMI: Thrombolysis vs Primary PCI Mortality differences
0
5
10
15
20
25
PCI
LYSIS
PAMIAge>65
PCATAge>70
GUSTOIIbAge>70
DeBoerAge>75
GRACEAge>75
%
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Reperfusion strategy in elderly patients in the real world
59
54
34
19
2231
57
9
15
0%
25%
50%
75%
100%
<55 55 - 75 >75
NO TREATPCITL
DEATH 7.5%
<55 0.8%
55-75 4.9%
>75 19.9%
Di Chiara A. EHJ 2003;24:1616
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(GRACE, Chest 2004)(GRACE, Chest 2004)
Tipici AtipiciTipici Atipici
%%50
40
30
20
10
0
50
40
30
20
10
0
< 65 anni
> 75 anni
< 65 anni
> 75 anni
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Safety Concerns in the Elderly ACS PatientsBleeding Risks by Age
N=74,271
4,5
10,3
14,1
9,7
17,9 18,5
0
5
10
15
20
<65 yrs 65-75 yrs > 75 yrs
% R
BC
Tra
nsfu
sion
Non-CABG Overall
4,5
10,3
14,1
9,7
17,9 18,5
0
5
10
15
20
<65 yrs 65-75 yrs > 75 yrs
% R
BC
Tra
nsfu
sion
Non-CABG Overall
Excluded CABG, transfer outs, missing dataExcluded CABG, transfer outs, missing dataPeterson, E ACC 2005Peterson, E ACC 2005
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1,7 3 4,26,14,3 5,7 6,7
12,3
0
5
10
15
20
25
30
35
40
45
<55 55-64 65-74 >=75
Bleeding Bivalirudin Bleeding UFH+GPI NNT
Patient Age
38 3740
16
Number Needed to Treat (NNT) and Risk Reduction of Major Bleeding with Bivalirudin vs. Heparin/GPI
Lopes RD et al. J Am Coll Cardiol. 2009 Mar 24;53:1021-30
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Conclusioni
� I pazienti anziani rappresentano una popolazione complessa in progressivo aumento
� L’incidenza e la prognosi delle malattie cardiovascolari sono più severe nei pazienti anziani
� La prevenzione delle malattie cardiovascolari riveste un ruolo cruciale negli anziani
� La rivascolarizzazione coronarica per via percutanea èefficace nell’anziano
� Il trattamento dei pazienti anziani con PCI primaria si èdimostrato superiore alla trombolisi
� L’età avanzata rimane un potente predittore di mortalità e di complicanze emorragiche
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Net Clinical BenefitBleeding Risk Subgroups
OVERALL
>=60 kg
< 60 kg
< 75
>=75
No
Yes
0.5 1 2
PriorStroke / TIA
Age
Wgt
Risk (%)
+ 37
-16
-1
-16
+3
-14
-13
Prasugrel Better Clopidogrel BetterHR
Pint = 0.006
Pint = 0.18
Pint = 0.36
Post-hoc analysis
Wiviott SD et al New Eng J Med 2007; 357: 2001-15Wiviott SD et al New Eng J Med 2007; 357: 2001-15
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Excessive Dosing of Antithrombotics by AgeExcessive Dosing of Antithrombotics by Age
12,5
28,7
8,512,5
3733,1
16,5
38,5
64,5
0
10
20
30
40
50
60
70
LMW Heparin UF Heparin GP IIb/IIIa
% E
xces
sive
Dos
e
< 65 yrs 65-75 yrs >75 yrs
12,5
28,7
8,512,5
3733,1
16,5
38,5
64,5
0
10
20
30
40
50
60
70
LMW Heparin UF Heparin GP IIb/IIIa
% E
xces
sive
Dos
e
< 65 yrs 65-75 yrs >75 yrs
Q1-Q2 2004 CRUSADE dataQ1-Q2 2004 CRUSADE data
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Very easy to find the elderly in the CCU…
21
31
13
7 7 62 2 2 2 1 1 1 1 0,5 0,4 0,3 0,3 0,2
0
20
40
60
STEMI
SCA NSTE
Scomp ensoFA/T
PSVBra
diari t
mi eDolo
re T
or.TV/F
VSin
cope
post-PCI/B
PAC
Alt ro
Embolia
Polm
.Arr
esto
CC
Shock
no S
CA
Mio-
peric
ard
itePost-
PM/A
ICD
Tampo
nam.
Dissez
i one
CADEnd
ocar
dite
%
332 CCUs 6986 patients
Mean age: 70 ±±±± 13 years
Median (range 25-75 °°°°): 72 (61-80) years
Age > 75 years: 39% of the patients
Casella G. J Cardiovasc Med 2010
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Crusade: ACS in Elderly
2,8
67,4
8,5
13,3
16,1
02468
1012141618
Death Death/MI CHF
<75 Years >75 Years
Kulkarni S et al ACC 2003 CRUSADE Presentation
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CCP (Shlipak, Ann Intern Med 2002 )CCP (Shlipak, Ann Intern Med 2002 )
< 1.5 1.5-2.5 >2.5 creatinina< 1.5 1.5-2.5 >2.5 creatinina
mor
talit
à1
anno
mor
talit
à1
anno
100
80
60
40
20
0
100
80
60
40
20
0
24%24%
46%46%
66%66%
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0
5
10
15
0 30 60 90 180 270 360 450
HR 0.81(0.73-0.90)P=0.0004
Prasugrel
Clopidogrel
Days
End
poin
t (%
)
12.1
9.9
HR 1.32(1.03-1.68)
P=0.03
Prasugrel
Clopidogrel1.82.4
138events
35events
Efficacy and SafetyN=13608
CV Death / MI / Stroke
TIMI Major NonCABG Bleeds
NNT = 46
NNH = 167
Wiviott SD et al New Eng J Med 2007; 357: 2001-15Wiviott SD et al New Eng J Med 2007; 357: 2001-15
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Riduzione degli eventi avversi nei pazienti trattati con statine
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Soggetto che fornisce assistenza in caso di necessità (val. %)
Fonte: indagine Censis, 2004
< 2% istituzioni
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-48-46
-28
-39-37
-50
-25
0Age >75 Renal
FailureFemale
UHFpre-treat Diabetes
Bivalirudin provides consistent relative risk reductionBivalirudin provides consistent relative risk reduction
30-day Major Bleeding
30-day bleeding and one-year mortality in Replace-2 high risk subgroups
30-day bleeding and one-year mortality in Replace-2 high risk subgroups
-41
-28
-47
-37
-48
Age >75RenalFailure Female UHF
pre-treatDiabetes
One-year Mortality
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The aging failing heart
Cardiac disease
Comorbidities and
Life- Stile
Normal aging
CV Changes
Complexity
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Strategie di Prevenzione del Rischio CCV GlobaleBergamo 13 Novembre 2010
Giuseppe Musumeci
USC Cardiologia Ospedali Riuniti di Bergamo
La malattia cardiovascolare nell’anziano: strategie di prevenzione e trattamento
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Fe
ma
le
UH
F p
ost
-PC
I
UA
MI<
12
hrs
IAB
P
Ag
e >
75
Ab
cixi
ma
b
Re
na
l Fa
ilure
Dia
be
tes
2,9
22,3 2,4
3
1,6 1,81,6
1,3
0
1,5
3
OROR
Factor associated to higher incidence of major bleeding
Montalescot et al. Heart 2005;91:89Montalescot et al. Heart 2005;91:89 Kinnaird et al. Am J Cardiol 2003;92:930Kinnaird et al. Am J Cardiol 2003;92:930Manoukian SV, Voeltz MD, Feit F et al. TCT 2006
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.
Mortalità ospedaliera Mortalità 6 mesi
Devlin G, Gore M, Elliott J et al. Eur Heart J 2008;29:1275-82
GRACE – Anziani con Sindrome coronarica acuta ad alto rischio
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Mortality benefit of myocardial revascularization in the Elderly
Extracted from Pfisterer M. Circulation 2004;110:1213-1218
0
2
4
6
8
10
0 4 6 8Time since intervention (years)
Pro
port
ion
with
out d
eath
Revascularized
Not revascularized
Log Rank p=0,0027
All patients
Revascularized 174 159 149 115 72 34Not revascularized 127 113 101 80 48 28
No. At risk
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Acute Coronary Care in the ElderlyA Scientific Statement From the
American Heart Association
Circulation 2007;115;2549-2569
≥ 75 years of age
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RCTs vs Observational studies
0
10
20
30
40
66-70 71-80 81-90 91-00
Decade
% A
ge>7
5Community Practice
Trials
Lee, JAMA, 2001
GRACE
VIGOUR RCT’s
CRUSADE
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n = 252
n = 229
Grines C. TCT; Washington DC 2005
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Age related impairments(common reasons for nonadherence
and lack of self-management)
• Visual and hearingimpairment (20-50%)
• Cognitive impairment(26-78%: dementia, depression, etc)
Possibly related to cerebral hypoperfusion and CVA
• Lack of social support: social isolation; marital functioning vs living alone
• Health illiteracy (25%): difficulties to understandwritten and oral informations concerning their illness and treatment
� “do you understand what I have told you?” is not enough
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Senior PAMI: 30- day Outcome Based on Age-Stratified Randomization
7,1 7,7 7,7
11,3 12
17
0
5
10
15
20
25
Death Death/CVA D/CVA/reMI
Age 70-80 (n=351)
%
PCI Lysis
19 2022
16 16
22
0
5
10
15
20
25
Death Death/CVA D/CVA/reMI
Age >80 (n=130)
%
PCI Lysis
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Annual Rate of First Heart Attackby Age, Sex, and Race in the U.S.
0
2
4
6
8
10
12
14
35-44 45-54 55-64 65-74
Years
Per
10
00
Per
son
s
White Men
Black Men
White Women
Black Women
Source: Atherosclerosis Risk In Communities (ARIC) study, 1987-94
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Rapporto ISTAT 2008
Italiani, i più anziani
• 20% di ultrasessantacinquenni
• 5,5% di ultraottantenni
• Aspettativa di vita: 78 anni uomini, 83 donne
• 85% degli anziani assume farmaci
http://www.istat.it/dati/catalogo/20081112_00/PDF/cap2.pdf
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Fried L. 2005
Heterogeneity of health with aging
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14,9
30,2
54,4
100
0102030405060708090
100
FSS
grade 1grade 2grade 3grade 4
Frailty and 1-year mortality
21,1
47,6
81,8
100
0102030405060708090
100
FSS
grade 1grade 2grade 3grade 4
Frailty and 1-year HF admissions
Log Rank 20,345; df 2; p<0,0001
FSS 1
FSS 2
FSS 3-4
FSS 1
FSS 2
FSS 3-4
Log Rank 41,207; df 2; p<0,0001
G.Pulignano et al Eur Heart J 2006
•deficit cognitivo, incontinenza urinaria e disturbi della motilità
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Zuccalà G et al Am J Medicine 2003; 115: 97-103.
Deficit cognitivo e prognosi di scompenso cardiacostudio GIFA Osservatorio Geriatrico Campano
Abete P et al,
Del Sindaco, et al.
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11-25% of older persons use 5 or more meds
simultaneously
•Multiple physicians, multiple drugs
•Errors in self-administration caused by age related impairments,
complexity of medication regimen, duration of treatment
•More than 20% of adverse drug reactions in the elderly are due to
drug interactions (Drug-drug / -nutrient /-alcohol)
•Multiple organ system changes (CV, GI, liver, kidney)
Pharmacodynamics /Pharmacokinetics
Polypharmacy and Drug interactions in elderly patients