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

Changes in global population from 2000 to 2030Percent Aged 65 and Over

US Census Bureau 2000

2000

2030

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

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

Cardiopatie: prima causa di morte e ricovero nell’anziano

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.

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

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

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

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

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

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

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

Rischio nei pazienti con sindrome coronarica acutaRelazione con l’età

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)

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

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

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

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

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

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

%

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

(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

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

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

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

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

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

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

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

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%

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

Riduzione degli eventi avversi nei pazienti trattati con statine

Soggetto che fornisce assistenza in caso di necessità (val. %)

Fonte: indagine Censis, 2004

< 2% istituzioni

-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

The aging failing heart

Cardiac disease

Comorbidities and

Life- Stile

Normal aging

CV Changes

Complexity

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

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

.

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

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

Acute Coronary Care in the ElderlyA Scientific Statement From the

American Heart Association

Circulation 2007;115;2549-2569

≥ 75 years of age

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

n = 252

n = 229

Grines C. TCT; Washington DC 2005

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

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

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

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

Fried L. 2005

Heterogeneity of health with aging

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

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.

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