trattamento delle sindromi coronariche acutesindromi...

Trattamento delle Sindromi Coronariche AcuteSindromi Coronariche Acute

nel paziente anziano

Stefano SavonittoDi i i di C di l i

Data: 10-11 maggio 2013

Evento: Novara - Baveno

Titolo: ACS Treatment elderlyAutore: Stefano Savonitto

Divisione di CardiologiaArcispedale S. Maria Nuova

Reggio Emilia

Proportion of men and women >85 year-old registered in the Swedish National hospital discharge registry

Rosengren A. Eur Heart J 2012;33:562

Comparing mean ages of Italian ACS registries and guideline-building trials

80-NSTEACS STEMI

75- women

men women

7468 68

55-6362 62 62 60 59 59

Eur Heart J Acute CV Care

BLITZ 4Eur Heart J

Acute CV Care 2012

BLITZ 4RITA III

Lancet2002

TIMI18

NEJM2001

ICTUSNEJM2005

TRITONLancet2009

HORIZONSNEJM2008

PLATOCirculation

Average enrolment / center / monthItalian Elderly

ACS Study

313 patients / 21 centres / 29 monthsYears

= 0.51 patients / centre / monthYears

2008-2010JACC Intv 2012

Years2005-2007

Eur Heart J 2010

266 patients / 23 centres / 33 months

= 0.34 patients / centre / month

302 patients / 14 centres / 59 monthsYears1996-2000

TIME studyElderly pts

= 0.37 patients / centre / month1996-2000Lancet 2002 Symptomatic

Stable CAD

2220 patients / 196 centres / 24 months

= 0.55 patients / centre / month

Years1998-2000NEJM 2000

Metanalysis of PPCI vs lysis in elderly patients

Bueno H, EHJ 2011;32:51-60

Senior PAMI: 30-day Outcome Based on Age-Stratified Randomizationased o ge St at ed a do at o

PCI Lysis

22 2220

PCI Lysis

19 2022

7,1 7,7 7,7

11,3 12

0Death Death/CVA D/CVA/reMI

Age 70-80 (n=351)

0Death Death/CVA D/CVA/reMI

Age >80 (n=130)

Primary angioplastyPAMI pooled analysis (1990-1998)

De Geare et al Am J Cardiol 2000;86:30–34

12-month outcomes

C it d i t All t litComposite endpoint All-cause mortality

roke Primary PCI

Thrombolysis

I or d

P=0.650.6C

P=0.31

Follow-up (days)360300240180120600

Bueno H, EHJ 2011;32:51-60

30-day mortality in STEMI by time

Mortality %

>= 75 yr

65 – 74 yr65 74 yr

< 65 yr

Women<65 Women 65-75 Women >75 Men<65 Men 65-75 Men >75

Men 65 Men 65 75 Men 75 Uppsala Clinical Research Centre 2005

Changes in the management of ACS in the elderly 2006 vs 2001: The Franche Comté Registry

Non-adjustedAdjusted for propensity score

STESTE

Schiele F, Eur Heart J 2009;30:987

>2006<2006

Changes 35-day survival in elderly pts with ACS 2001 vs 2006: The Franche Comté Registry

Schiele F, Eur Heart J 2009;30:987

5-year death/MI in the FIR collaboration

SI= selective invasiveRI= routine invasive

>75>75y

65-74y65 74y

Damman P et al. Heart 2012;98:207-13

5-year death/MI in the FIR collaboration according to age and genderaccording to age and gender

SI= selective invasiveRI= routine invasive

65-74y

<65y<65y

D P t l H t 2012 98 207 13

Damman P et al. Heart 2012;98:207-13

Italian Elderly

ACS Study

Early aggressive vs initially conservative In elderly patients with NSTEACS and elevated Tn

Survival to primary endpoint in troponin positive patients

HR 0.43; 95% CI 0.23-0.80Logrank P=0.015

Savonitto S. JACC Intv 2012;5:906-16

Italian Elderly

ACS Study

Kaplan Meier survival without primary endpointaccording to actual revascularization

ACS Study

Revascularization (n=119)Revascularization (n 119)Event rate 22%

No revascularization (n=194)Event rate 37%

Logrank P=0.0077

Italian Elderly

ACS Study

All-cause and cardiac mortality inItalian Elderly ACS and PARTNER

30%Mean age 82 years in both cohorts Mean age 84 years

25%- 71%

All cause

Cardiac46%

15% 85%15%-

10%- 23.816 9

13.4 11.116.9

0-Trial

N=313RegistryN=332

PARTNER (surg)N=351

NEJM 2012, March 28Morici N, Am J Cardiol 2013

Cumulative risk estimate of death up to 405 days of follow up

(Morici N, Am J Cardiol 2013)

Italian Elderly

ACS Study

0.18Cumulative incidence of Death

120/645 pts (18.6%)

0.14120/645 pts (18.6%)

0.080.10

Cumulative incidence of CV Death

97/645 pts (15.0%)E

0.040.06

Cumulative incidence of NCV Death

Days0 60 120 180 300 360240 4050.00

0.02 Cumulative incidence of NCV Death

23/645 pts (3.5%)

Contribution of cardiac death to overall death in the elderly(each column represents the % of cardiac death)

100-General population Hospitalised patients

menwomengeneral

3739 40 4039

0-ISTAT CDC Medicare Italian ElderlyBreastProstate HipISTAT>75y

CDCGorina Y

Aging trends 2006

Medicare>67y

Newschaffer CJJ Nat Cancer Inst 2000

Italian ElderlyNSTEACS

>75yAm J Cardiol 2013

Breast cancer>80y

J Clin Oncol 2011

Prostate cancer>65y

Newschaffer CJJ Nat Cancer Inst 2000

Hipfracture

>65yBMJ Musc.Skel Dis

Independent predictors of death at logistic regressionIn the whole study cohort (Morici N, Am J Cardiol 2013)

Italian Elderly

ACS Study

All-cause death(N° of events=120)

Ejection Fraction* 29.989

Wald χ2

HR 95% CI p-value predictiveinformation

0.952 0.935-0.969 <0.001 35%

ACS Study

Blood haemoglobin* 10.664

Age* 6.607

Creatinine Clearance* 4.716

0.845 0.763-0.935 0.001 13%

1.054 1.013-1.098 0.010 8%

0.986 0.973-0.999 0.030 6%

Cardiovascular death(N° of events=97)

Ejection Fraction 27 109 0 950 0 932-0 969 <0 001 45%Ejection Fraction 27.109

Creatinine Clearance 6.215

Blood haemoglobin 3.372

0.950 0.932-0.969 <0.001 45%

0.982 0.968-0.996 0.013 10%

0.900 0.805-1.007 0.066 6%

1 032 0 986 1 079 0 174 3%

Noncardiovascular death(N° of events=23)

Age 1.844

i 18 8

1.032 0.986-1.079 0.174 3%

0 96 0 4 2 0 3 0 001 42%Blood haemoglobin 18.875

Age 13.151

Ejection Fraction 4.559

0.596 0.472-0.753 <0.001 42%

1.165 1.073-1.265 <0.001 29%

0.952 0.910-0.996 0.033 10%

0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5

Hazard Ratio (HR)

Mechanisms Leading to Pharmacokinetic Variations of Antithrombotic Drug Effects in the Elderlyg y

Capodanno & Angiolillo JACC 2010;56:1683 1692

Capodanno & Angiolillo. JACC 2010;56:1683-1692

Safety Concerns in the Elderly with ACSBleeding Risks by Age

17,9 18,520

14,115sion

N=74.271N=74.271

10,39,710Tr

0<65 yrs 65-75 yrs > 75 yrs

Non-CABG Overall

GP IIb/IIIa inhibitors in the Elderly

Pooled data from EPIC, CAPTURE, EPILOG and EPISTENT Trial

AbciximabPlacebo

11,8 11,6 11,8

6,15,35

5,36,5

4,43,7

<55 55 - 70 >70

<55 55 - 70 >70O

nAge (y) Age (y)

Mak et al, Drugs Aging 2002

30-day bleeding and one-year mortality high risk subgroups

30-day Major Bleeding UHF

One-year Mortality

Age >75 FemaleUHFpre-treat Diabetes Age >75

RenalFailure Female

UHFpre-treat DiabetesRenal

Failure

Lincoff AM, JAMA 2004;292:696

Cangrelor in The Elderly?

Non–ST-segment elevation acute coronary syndrome in 25.7% (5.7% had unstable angina), and STEMI in 18.2%.

Bhatt DL et al. NEJM 2013 Ahead of print

RADIAL VERSUS FEMORAL APPROACH: META-ANALYSIS OF RANDOMIZED TRIALS

Major bleeding 0.05 2.3 0.27 (0.16-0.45) <0.001D+MI+stroke 2.5 3.8 0.71 (0.49-1.01) 0.058D MI stroke 2.5 3.8 0.71 (0.49 1.01) 0.058Death 1.2 1.8 0.74 (0.42-1.30 0.29MI 2.0 2.9 0.76 (0.49-1.17) 0.21Stroke 0.1 0.5 0.39 (0.09-1.75) 0.22Access site crossover

5.9 1.4 3.82 (2.83-5.15) <0.001crossoverInability to cross the lesion

4.7 3.4 1.31 (0.87-1.96) 0.20

N= 4461

Absolute RR 1.8% (95% CI 1.0-2.5%, p= 0.001),

NNT =56 to prevent one major bleeding

Jolly SS, Am Heart J 2009; 157:132-40

Revascularization procedures Revascularization procedures during index admissionduring index admission

ItalianItalian ElderlyElderly

ACSACS StudyStudyACSACS StudyStudy

100100--9090--8080--7070--

Early Early aggressiveaggressive

9494 9696

6060--5050-- 9696 97979797 100100

InitiallyInitiallyConservativeConservative

4040--3030-- 7070

96967878

DESDES54%54%

DESDES56%56%2020--

1010--00

54%54% 56%56%

00--Radial approachRadial approach stentingstenting Procedural Procedural

successsuccessPCIPCI

ProceduralProceduralsuccesssuccessCABGCABG

PCIPCI CABGCABG

Savonitto S. JACC Intv 2012; 5:906-16

Antithrombotic treatments during index admission

Italian Elderly

ACS Study

Early Aggressive (n=154)

Initially Conservative (n=159)

Drugs %

Aspirin 95 99Ticlopidine 4.6 1.94.6 1.9Clopidogrel 90 92

Unfractionated heparin 25 24Unfractionated heparin 25 24Enoxaparin 64 59

GPIIb/IIIa inhibitor 17 (24 in PCI) 6 (17 in PCI)Bivalirudin 3.8 1.3

Fondaparinux 8.5 8.5

Adverse clinical events during index hospitalizationItalian Elderly

ACS Study

Early Aggressive (n=154)

Initially Conservative (n=159)

Death 8 (5 2) 5 (3 1)

Death 8 (5.2) 5 (3.1)Myocardial (re)infarction 3 (1.9) 5 (3.1)

Severe recurrent ischemia 1 (0.6) 15 (9.4)Heart failure 11 (7.1) 4 (2.5)

0.0004

0.06( ) ( )Cardiac arrhythmia 3 (1.9) 3 (1.9)

Any stroke / Disabling 2 / 0 1 / 0NAny stroke / Disabling stroke

2 / 0 1 / 0TIMI major bleeding 0 1 (0.6)

CABG-related bleeding/transfusion

4 (2.6) 0

Cumulative risk estimate of death up to 405 days of follow up

(Morici N, et al. Submitted)

Italian Elderly

ACS Study

0.18Cumulative incidence of Death

120/645 pts (18.6%)

0.14120/645 pts (18.6%)

0.080.10

Cumulative incidence of CV Death

97/645 pts (15.0%)E

0.040.06

Cumulative incidence of NCV Death

Days0 60 120 180 300 360240 4050.00

0.02 Cumulative incidence of NCV Death

23/645 pts (3.5%)

Reduced platelet inhibition on clopidogrel in elderly patients (the SENIOR PLATELET study)in elderly patients (the SENIOR PLATELET study)

Silvain J. Eur Heart J 2012; 33:1241-9

Excess of upper GI complications with low-dose aspirinDepending on previous clinical history

Patrono C. NEJM 2005

Bleeding complications in CHARISMA

Becker RC. Circulation 2010;121:2575

Bleeding complications in CHARISMA

Becker RC. Circulation 2010;121:2575

Wiviott SD, NEJM 2007;357:2001

TIMI Major non-CABG bleedingafter day 3 for prasugrel by age

Wiviott SD, NEJM 2007;357:2001

Overall efficacy and safety in elderly patients

Husted S, Circ CV Qual Outcomes 2012;5:680

Newer antiplatelet treatments compared to clopidogrel in ACS: Patients >75 y.o.

25- 25-PLATO (n=2878) TRITON (n=1809)

clopid clopid

20- 20-Adj HR 0.89(IC 0.74-1.08)

HR 0.94(CI 0.75-1.18)

ticag prasug

15- 15-

10-18.3 17.2

Adj HR 1.18(IC 0.73-1.59)

HR 1.36

03.4 4.2

7.1 8.3(CI 0.81-2.27)

0- 0-D+MI+stroke PLATO non-CABG

major bleedingD+MI+stroke TIMI non-CABG

major bleeding

Husted S. Circ CV Qual Outcomes 2012;5:680 Wiviott S. N Engl J Med 2007;357:2001

Prasugrel 5 mg improves platelet inhibition in the elderly(patients on chronic treatment)

Capranzano P. Thromb Haemost 2011; 106:1149-57

Platelet inhibition studyPrasugrel 30+5 mg vs clopidogrel 300+75 mgPrasugrel 30 5 mg vs clopidogrel 300 75 mg

G b l PA JAMA 2012 308 1785 94

Gurbel PA. JAMA 2012;308:1785-94

Overall efficacy and safety in the elderlyOverall efficacy and safety in the elderlyFigures derived by subtraction from the main paperFigures derived by subtraction from the main paper

30-25-20

prasugrel5 mg

clopidogrel75 mg

20-15-10- 24.6 24.1

Ischemicendpoints

CVD+MI CVD MI stroke All cause

13.5 14.5 13.8 12.73.0 2.2

17.0 19.1endpoints

CVD+MI+stroke

CVD MI stroke All-causemortality

2.0-Bleeding1.0-

0-GUSTO

0.8 1.3 1.8 1.80.3 0.5 0.6 0.6

2.6 3.0g

endpoints

GUSTO SEVERE -LT

TIMI Maj TIMI fatal stroke TIMI Maj + min

2 000 patients2 000 patients >>75 years75 yearsRCTRCT

Italian Elderly

ACS-2 Study2,000 patients 2,000 patients >>75 years75 yearswith ACS treated invasivelywith ACS treated invasively

webweb

ACS 2 y

ClopidogrelClopidogrel Pras grelPras grel

webwebrandomrandom

ClopidogrelClopidogrel300+75 mg300+75 mg

PrasugrelPrasugrel60+5 mg60+5 mg

1212--month month 1212--month month followfollow--upup followfollow--upup

PrimaryPrimary endpointendpointth itth it ff llll t litt lit di ldi l ( )( )MIMI di blidi bli t kt k ddthe composite the composite ofof allall--causecause mortalitymortality, , myocardialmyocardial (re)(re)MIMI, , disablingdisabling strokestroke and and

rere--hospitalizationhospitalization forfor cardiovascularcardiovascular causescauses or severe or severe bleedingbleeding withinwithin 12 12 monthsmonths

PI: S. Savonitto, S. De Servi

PI: S. Savonitto, S. De ServiCoordinating Center: IRCCS Arcispedale S. Maria Nuova, Reggio Emilia

•78 y.o. man with recurrent bladder cancer and indication to re-TURB• July 2011, NSTEACS: PCI + BMS proximal-mid LAD, heavily calcified• October 2011, NSTEACS with anterior ST depression: severe restenosis LAD and, pAntero-apical akinesia; EF 0.45; moderate mitral rigurgitation• Bypass surgery: LIMA-LAD offpump, left toracotomy.

Day 3 post-surgery

Donna di 85 anni senza patologie di rilievo, autosufficiente e attivaI° episodio di angor con pre-sincope. Centro spoke, domenica mattina.

Donna di 85 anni senza patologie di rilievo, autosufficiente e attivaI° episodio di angor con pre-sincope. Centro spoke, domenica mattina

Terapia con nitrato, ASA, Clopidogrel 300 mg.Regressione del dolore, invio a hubg ,

A centro hub: ripresa di dolore

A centro hub: ripresa di dolore, coronarografia immediata

Coronarografia immediata per via radiale destra

Coronaria destrarelativamenterelativamentepiccola, con stenosi 70%

FE 0.55

Minima elevazione TnTelevazione TnT

Coronarografia immediata per via radiale destra

Coronaria destrarelativamente

Stop clopidogrelInizia tirofiban

relativamentepiccola, con stenosi 70% Indicazione a

AMIs-IVA in i it t iFE 0.55

Minima elevazione TnT

minitoracotomia senza CEC+ PCI Cx

elevazione TnTPaziente stabile

Intervento rinviatoIntervento rinviatodi 48 ore per wash-out clopidogrel

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