Il Management delle

Sindromi Coronarie Acute

oggi

Il paziente anziano e con

IRC grave

Filippo M. Sarullo

U.O. di Riabilitazione Cardiovascolare

Ospedale Buccheri La Ferla FBF

Palermo

NSTE-ACS: ETA’ & Mortalità

VIGOUR trial and GRACE

Early Invasive in Elderly: ESC 2007

TACTIS TIMI 18: ha escluso pazienti con creatinina > 2.5, BBSn, scompenso

cardiaco grave, importanti malattie sistemiche, pregresso ictus/emorragia

cerebrale/sanguinamento GI, TAO/ticlopidina/clop.

% Bleeding: 16.6% vs 6.5%

% STROKE n.s. (1 vs 2, su 139 pz!)

NSTE-ACS: ETA’ & Comorbilità

CRUSADE registry

BLEEDING RISK in NSTE-ACS

+ Anemia

La Finestra Terapeutica dell’Anziano

FT: intervallo di sicurezza tra la dose efficace minima di un farmaco e la

sua concentrazione tossica minima.

Anziani

Prasugrel: analisi dei sottogruppi per età del TRITON-TIMI38, ha evidenziato nei pz > 75aa un incremento delle emorragie con perdita del beneficio clinico

Ticagrelor: Studio Elderly (2012)

Husted S, et al. Circ Cardiovasc Qual Outcomes 2012;5:680–688.

PLATO elderly patient subgroup analysis:

demographics, treatment and procedures

• Of the 18,622 patients in the PLATO study for whom age data was available,

2878 (15.5%) were elderly [Husted 2011:B]

- Elderly patients were defined as being aged ≥75 years old

• Several notable differences were observed in the elderly subgroup compared

with the younger patient subgroup[Husted 2011:C]

- Greater proportion of women

- Lower body weight

- Increased prevalence of CV risk factors and renal disease

- More likely to have a history of prior ischaemic CV events or CV disease

- Reduced glomerular filtration rate

- Elderly patients were less likely to present with STEMI[Husted 2011:C]

• Initial treatment plans for elderly patients were less likely to involve an invasive

strategy[Husted 2011:C,D]

ACS, acute coronary syndromes; CV, cardiovascular; STEMI, ST-segment elevation myocardial infarction. Husted S, et al. J Am Coll Cardiol 2011;57:E1099.

PLATO elderly subgroup: 2878 pts (15.5%) Caratteristiche demografiche e cliniche

Husted S et al . JACC 2011; 57: E 1099

> 75 aa < 75 aa p

§

§

25 35 45 55 65 75 85 95

PLATO elderly patient subgroup analysis: Primary composite endpoint according to age

Husted S, et al. J Am Coll Cardiol 2011;57:E1099; Wallentin L, et al. N Engl J Med 2009;361:1045–1057

Age (years)

CV

death

, M

I o

r str

oke (

%)

35

30

25

20

15

10

5

0

Ticagrelor Clopidogrel

Primary endpoint benefit with ticagrelor was consistent with the overall PLATO trial results

[Husted 2011:H; Wallentin 2009:H]

No interaction between age and treatment was observed [Husted 2011:I]

p for interaction = 0.2163

CV, cardiovascular; MI, myocardial infarction.

PLATO elderly patient subgroup analysis:

Association of age with bleeding

Events, n

Age <75

years old, %

(n=15,744)

Age ≥75

years old, %

(n=2878)

HR (95% CI)

Safety endpoints

Major bleeding

Fatal bleeding

Life-threatening/fatal bleed

Non-CABG-related major bleeding

CABG-related major bleeding

1886

43

968

665

1272

11.0

0.2

5.6

3.5

7.8

13.8

0.8

7.1

7.7

6.7

Age ≥75 years better Age ≥75 years worse

CABG, coronary artery bypass graft; CI, confidence interval; HR, hazard ratio.

0.5 1.0 2.0 7.0 1.5 3.0

Elderly patients have a greater risk of non-CABG-related major bleeding and fatal bleeding compared with younger patients[Husted 2011:I]

Husted S, et al. J Am Coll Cardiol 2011;57:E1099

PLATO elderly patient subgroup analysis: Major bleeding according to age

Ticagrelor Clopidogrel

Majo

r b

lee

din

g (

%)

Major bleeding occurred with similar frequency in the ticagrelor and clopidogrel groups as observed in the overall PLATO population [Wallentin 2009:I; Husted 2011:L]

No interaction between age and treatment was observed [Husted 2011:L]

25

20

15

10

5

0

25 35 45 55 65 75 85 95

p for interaction = 0.9971

Age (years)

Husted S, et al. J Am Coll Cardiol 2011;57:E1099

• In elderly ACS patients, the benefits of ticagrelor over clopidogrel

were consistent with the overall PLATO study[Husted 2011:M]

• The efficacy of ticagrelor compared with clopidogrel was independent

of age[Husted 2011:M]

- Primary composite endpoint of CV death, MI or stroke was lower

with ticagrelor compared with clopidogrel, irrespective of age

- All-cause mortality, CV death, MI and definite stent thrombosis

were reduced by ticagrelor compared with clopidogrel,

irrespective of age

• Major bleeding was similar in ticagrelor- and clopidogrel-treated

patients regardless of age[Husted 2011:M]

ACS, acute coronary syndromes; CV, cardiovascular; MI, myocardial infarction; Husted S, et al. J Am Coll Cardiol 2011;57:E1099.

Summary of the PLATO elderly patient subgroup analysis

PLATO elderly subgroup: Age and clinical outcomes

Ticagrelor better Clopidogrel better

Husted S, et al. Circ Cardiovasc Qual Outcomes 2012;5:680–688

PLATO elderly patient substudy: Primary composite endpoint according to age

1.3 1.2 1.0 1.1 0.8 0.6 0.4

HR (95% CI) 0.5 0.7 0.9

1.6 1.4 1.2 1.0 0.8 0.6 0.4

Ticagrelor better Clopidogrel better

Husted S, et al. Circ Cardiovasc Qual Outcomes 2012;5:680–688

HR (95% CI)

PLATO elderly patient substudy: Major bleeding according to age

Anziani

Ticagrelor, in base allo studio Elderly

ottiene, anche nei pazienti oltre i 75aa, un vantaggio rispetto al clopidogrel in termini di - end-point combinato - mortalità totale senza incremento dei sanguinamenti maggiori

17.3%

22.0%

Renal function and outcomes in PLATO:

Primary composite endpoint

James S, et al. Circulation 2010;122:1056–1067; Wallentin L, et al. N Engl J Med 2009;361:1045–1057

Days after randomisation

Normal renal function Ticagrelor Clopidogrel HR (95% CI) = 0.90(0.79–1.02)

7.9% 8.9%

0 60 120 180 240 300 360

25

20

15

10

5

0

CV

de

ath

, MI

or

stro

ke (

%)

CKD Ticagrelor Clopidogrel HR (95% CI) = 0.77(0.65–0.90)

p for interaction = 0.13

L’efficacia del ticagrelor sull’EP primario è confermata nei pz con IRC

Non vi sono interazioni tra funzione renale e terapia (p=0.13)

James S, et al. Circulation 2010;122:1056–1067

End-point primario di efficacia in funzione della

funzionalità renale (CrCl)

Ticagrelor better

Clopidogrel better

Risk of CV death, stroke or MI HR (95% CI)

30

40

50

60

70

80

90

100

CrCl (mL/min)

0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 0.4

Incr

easi

ng

ren

al im

pai

rmen

t

Non vi sono interazioni tra funzione renale e terapia (p=0.13)

p for interaction = 0.92

Sanguinamenti e funzionalità renale nel Plato

15.1% 14.3%

Non-CABG TIMI bleeding’ et al. James S et al - Circulation 2010;122:1056–1067

Days after randomisation

0 60 120 180 240 300 360

Maj

or

ble

ed

ing

(%)

25

20

15

10

5

0

CKD Ticagrelor Clopidogrel HR (95% CI) = 1.07 (0.88–1.30)

Normal renal function Ticagrelor Clopidogrel HR (95% CI) = 1.08 (0.96–1.22)

9.8%

10.6%

La frequenza di sanguinamenti è simile nei 2 gruppi ticagrelor e clopidogrel

• Il ticagrelor è un antiaggregante più efficace rispetto al clopidogrel nelle SCA

• indipendentemente dalla funzionalità renale

• con un beneficio maggiore nei pz con funzionalità renale compromessa

• senza necessità di ridurre il dosaggio per prevenire sanguinamenti maggiori.

• Non sono però disponibili informazioni riguardo ai pazienti in trattamento dialitico.

Ticagrelor ed insufficienza renale nelle SCA

CONCLUSIONI Nel paziente anziano con SCA, la insufficienza renale è sempre

importante, anche se lieve: calcolare il GFR!

In assenza pazienti anziani, con grave insufficienza renale e SCA, la

gestione clinica è individualizzata (rischio/beneficio). Questi pazienti

non rappresentano una importante percentuale degli anziani ricoverati

per SCA, ed hanno una mortalità estremamente elevata, a prescindere

dal tipo di trattamento.

Prima di un trattamento invasivo, oltre alle comorbilità, si deve

sempre tenere conto delle condizioni geriatriche (autonomia, qualità

di vita, decadimento cognitivo), della volontà e della spettanza di vita

del paziente.

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