GESTIONE DEL PAZIENTE CON NSTEMI -...

GESTIONE DEL PAZIENTE GESTIONE DEL PAZIENTE CON NSTEMICON NSTEMI

Dr.ssa MARIALAURA BUSCEMISC CardiologiaDipartimento Cardio-Toracico-Vascolare

Strategia invasiva precoceo strategia conservativa/invasiva selettiva???

- Sostenitori dell’atteggiamento invasivo

precoce

- Sostenitori dell’atteggiamento invasivo

selettivo

TACTICSTACTICS--TIMI 18 Study DesignTIMI 18 Study Design

2220UA/

NSTEMI

RoutineInvasive

Conservative

PCI/ CABG

Cath/ PCI/ CABG

Medical Rx

Medical Rx

Endpoints

6 mosRandomize

-24 hrs

Chest pain

4- 48 108hrs hrs

Early Tirofiban, ASA, Hep

Angio

Hour0

ETT

+ischemia

BaselineBaselineTroponinTroponin

Cannon CP, et al. N Engl J Med 2001;344:1879–87.

0 1 2 3 4 5 6Time (months)

0

4

8

12

16

20

% P

atie

nts

CONS

INV

O.R 0.7895% CI (0.62, 0.97)

p=0.025

19.4%

15.9%

TACTICS: Primary EndpointTACTICS: Primary EndpointDeath, MI, Rehosp for ACS at Death, MI, Rehosp for ACS at 6 Months6 Months

••↓↓ Death, MI, and Death, MI, and rehosprehosp for an ACS at 6 for an ACS at 6 momo for for invinv strategystrategy

••Benefit in medium and highBenefit in medium and high--risk patientsrisk patients ((TnTTnT ↑↑ of > 0.01 of > 0.01 ngng/mL, /mL, STST--segment deviation, TIMI risk score > 3)segment deviation, TIMI risk score > 3)

••↓↓ Death/MI at 6 Death/MI at 6 momo for older adults with early for older adults with early invinv strategystrategy

••Benefit of early Benefit of early invinv strategy for highstrategy for high--risk women (risk women (↑↑ TnTTnT); low); low--risk risk women tended to have worse outcomes, women tended to have worse outcomes, inclincl ↑↑ risk of risk of major major bleedingbleeding

Cannon CP, et al. N Engl J Med 2001;344:1879–87.

TACTICSTACTICS--TIMI 18 ResultsTIMI 18 Results

Third Randomized Intervention Third Randomized Intervention Treatment of Angina (RITATreatment of Angina (RITA--3)3)

•• 1,810 moderate1,810 moderate--risk ACS patientsrisk ACS patients

•• Early Early invinv (<72 hours) or (<72 hours) or conservconserv (ischemia(ischemia--driven) strategydriven) strategy

•• Exclusions: CKExclusions: CK--MB > 2X ULN @ randomization, new QMB > 2X ULN @ randomization, new Q--waves, MI w/in 1 waves, MI w/in 1 momo, PCI w/in 1 y, any prior CABG, PCI w/in 1 y, any prior CABG

•• ↓↓ Death, MI, & refractory angina for Death, MI, & refractory angina for invinv strategy at 1 ystrategy at 1 y

―― Benefit driven primarily by Benefit driven primarily by ↓↓ in refractory anginain refractory angina

•• ↓↓ Death/MI at 5 y for early Death/MI at 5 y for early invinv armarm

•• No benefit of early No benefit of early invinv strategy in womenstrategy in women

Fox KA, et al. Lancet 2002;360:743–51. Fox KA, et al. Lancet 2005;366:914–20 (5-y results).

RITA-3 (5 Year Follow-up)

Fox KA, et al. Lancet 2005;366:914–20. Reprinted with permission from Elsevier.

DeathDeathOR 0.76 (0.58OR 0.76 (0.58--1.00) P = 0.0541.00) P = 0.054

DeathDeath15.1%15.1%

12.1%12.1%

410UA/

NSTEMI

EarlyInvasive

(med 2,4 h)

Delayed invasive/cooling off(med 86 h)

Aspirin, heparin,

clopidogreland tirofiban

Intracoronary Stenting with Intracoronary Stenting with Antithrombotic Regimen CoolingAntithrombotic Regimen Cooling--off off

Study (ISARStudy (ISAR--COOL)COOL)•• ↓↓ Death/MI at 30 d for Death/MI at 30 d for

early early angioangio group group

•• Diff in outcome Diff in outcome attributed to events that attributed to events that occurred before occurred before cathcath in in the the ““cooling offcooling off”” group, group, which supports rationale which supports rationale for intensive medical for intensive medical rxrx& very early & very early angioangio

Neumann FJ, et al. JAMA 2003;290:1593–9. LD = loading dose.

Invasive versus Invasive versus ConservativConservativTreatment in Unstable coronary Treatment in Unstable coronary

Syndromes (ICTUS)Syndromes (ICTUS)

•• 1,200 high1,200 high--risk ACS patients risk ACS patients

•• Routine Routine invinv vsvs selective selective invinv strategystrategy

•• Meds: aspirin, Meds: aspirin, clopidogrelclopidogrel, LMWH, and lipid, LMWH, and lipid--lowering lowering rxrx; ; abciximababciximab for for revascrevasc patientspatients

•• No No ↓↓ death, MI, and ischemic death, MI, and ischemic rehosprehosp at 1 y and longerat 1 y and longer--term term followfollow--up by routine up by routine invinv strategystrategy

•• MI in early invasiveMI in early invasive

de Winter RJ, et al. N Engl J Med 2005;353:1095–104. Hirsch A, et al. Lancet 2007;369:827–35 (follow-up study). LOE = level of evidence.

TIMACS: Effect of early TIMACS: Effect of early vsvs delayed delayed intervention on death, MI, or strokeintervention on death, MI, or stroke

•• Routine early (angiography Routine early (angiography ≤≤24 h) vs. delayed intervention in 24 h) vs. delayed intervention in

ACS ACS ptspts (3031)(3031)

•• Death, MI, or stroke at 6 months: 9.6% routine early vs. 11.3% Death, MI, or stroke at 6 months: 9.6% routine early vs. 11.3%

delayed (HR: 0.85; p=0.15)delayed (HR: 0.85; p=0.15)

•• Death, MI, or refractory ischemia at 6 months (secondary Death, MI, or refractory ischemia at 6 months (secondary

outcome): 9.5% routine early vs. 12.9% delayed (HR: 0.72; outcome): 9.5% routine early vs. 12.9% delayed (HR: 0.72;

p=0.003) p=0.003)

Mehta SR, et al. NEJM 2009;360:2165–75.

TIMACS: Effect of early TIMACS: Effect of early vsvs delayed delayed intervention on death, MI, or strokeintervention on death, MI, or stroke

RACCOMANDAZIONI PER LA DIAGNOSI E LA STRATIFICAZIONE DEL RISCHIO

Early Risk StratificationEarly Risk Stratification

Patients who present with chest discomfort or Patients who present with chest discomfort or other ischemic symptoms should undergo early other ischemic symptoms should undergo early risk stratification for the risk of cardiovascular risk stratification for the risk of cardiovascular eventsevents (e.g., death or [re]MI) that focuses on (e.g., death or [re]MI) that focuses on history, including history, including anginalanginal symptoms, physical symptoms, physical findings, ECG findings, and biomarkers of findings, ECG findings, and biomarkers of cardiac injury, and results should be considered cardiac injury, and results should be considered in patient management.in patient management.

Use of riskUse of risk--stratification models, such as the stratification models, such as the TIMI or GRACE risk score or PURSUIT risk TIMI or GRACE risk score or PURSUIT risk model, can be usefulmodel, can be useful to assist in decision to assist in decision making with regard to treatment options in making with regard to treatment options in patients with suspected ACS. patients with suspected ACS.

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

ACC/AHA Focus Update of the GL for NSTEMI 2012


• Age ≥ 65 years

• At least 3 risk factors for CAD

• Prior coronary stenosis of ≥ 50%

• ST-segment deviation on ECG presentation

• At least 2 anginal events in prior 24 hours

• Use of aspirin in prior 7 days

• Elevated serum cardiac biomarkers

Variables Used in the TIMI Risk Score

TIMI Risk

Score

All-Cause Mortality, New or Recurrent MI, or Severe Recurrent Ischemia Requiring Urgent

Revascularization Through 14 Days After Randomization %0-1 4.7

2 8.33 13.2

4 19.9

5 26.2

6-7 40.9

TIMI Risk Score

Mortality in hospital and at 6 months according

to the GRACE risk score

Crusade score of in-hospital major bleeding

Risk of major bleeding across the spectrum of

CRUSADE bleeding score

Decision-making algorithm in ACS

Recommendations for invasiveevaluation

and revascularization

Criteria for high risk with indicationfor invasive management

Invasive Recurrent angina/ischemia at rest with low-level activities despite intensive medical therapy

Elevated cardiac biomarkers (TnT or TnI)New/presumably new ST-segment depressionSigns/symptoms of heart failure or new/worsening mitral regurgitationHigh-risk findings from noninvasive testingHemodynamic instabilitySustained ventricular tachycardiaPCI within 6 monthsPrior CABGHigh risk score (e.g., TIMI, GRACE)Reduced left ventricular function (LVEF < 40%)

Conservative Low risk score (e.g., TIMI, GRACE)Patient/physician preference in the absence of high-risk features

Selection of Initial Treatment Strategy: Initial Invasive Versus Conservative Strategy


Initial Conservative Versus InitialInitial Conservative Versus InitialInvasive StrategiesInvasive Strategies

An early invasive strategy* is indicated in An early invasive strategy* is indicated in UA/NSTEMI patients who have refractory UA/NSTEMI patients who have refractory angina or hemodynamic or electrical instability angina or hemodynamic or electrical instability (without serious comorbidities or (without serious comorbidities or contraindications to such procedures).contraindications to such procedures).

An early invasive strategy* is indicated in initially An early invasive strategy* is indicated in initially stabilized UA/NSTEMI patients (without serious stabilized UA/NSTEMI patients (without serious comorbidities or contraindications to such comorbidities or contraindications to such procedures) who have an elevated risk for procedures) who have an elevated risk for clinical events.clinical events.

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

*Diagnostic angiography with intent to perform revascularization.



SCASCA : : NSTEMI NSTEMI –– ANGINA INSTABILEANGINA INSTABILERischio ALTORischio ALTO Rischio MEDIORischio MEDIO--ALTOALTO Rischio BASSO Rischio BASSO

Angina ricorrente / persistente Angina ricorrente / persistente TroponinaTroponina elevata Assenza di doloreelevata Assenza di doloreST sottost >0,5 mm o T profonde negative Alterazioni ST / TST sottost >0,5 mm o T profonde negative Alterazioni ST / T ((sintsint. o silenti) Assenza di alterazioni ST / T. o silenti) Assenza di alterazioni ST / TSintomi di scompenso e/o di instabilitSintomi di scompenso e/o di instabilitàà Diabete Diabete TroponinaTroponina negativa anche a 12 orenegativa anche a 12 ore

emodinamica Gemodinamica GRF < 60 ml/min Assenza di sRF < 60 ml/min Assenza di sintomi di scompensointomi di scompensoTV o FV TV o FV FE < 40%FE < 40%

Angina precoce post IMAAngina precoce post IMAPregressa PTCA (6 mesi) o CABGPregressa PTCA (6 mesi) o CABG

TERAPIA TERAPIA TERAPIA TERAPIATERAPIA TERAPIAO2 / Morfina (se necessari) Nitrati O2 / Morfina (se necessari) Nitrati e.v.e.v. / / osos (Nitrati)(Nitrati)Nitrati e.v. Nitrati e.v. Betabloccanti / Calcioantagonisti Betabloccanti /Betabloccanti / Calcioantagonisti Betabloccanti / CalcioantagonistiCalcioantagonistiBetabloccanti / Calcioantagonisti ASA Betabloccanti / Calcioantagonisti ASA ASAASA

Ace.inibitoriAce.inibitori AceAce--inibitori Aceinibitori Ace--inibitoriinibitoriASA 300 mg. ASA 300 mg. e.ve.vTicagrelorTicagrelor o o plasugrelplasugrel TicagrelorTicagrelor o o plasugrelplasugrel ClopidogrelClopidogrel o o ticagrelorticagrelor

(se noto quadro coronarico, (se noto quadro coronarico, ClopidogrelClopidogrelin particolare nei diabetici) (se gin particolare nei diabetici) (se gli altri non si possono dare) li altri non si possono dare) ClopidogrelClopidogrel (se gli altri non si possono dare) (se gli altri non si possono dare)

Fondaparinux / Fondaparinux / EnoxaparinaEnoxaparina//bivalirudinabivalirudina FondaparinuxFondaparinux / / EnoxaparinaEnoxaparina//bivalirudunabivalirudunaENF / ENF / EnoxaparinaEnoxaparina TirofibanTirofiban / / EptifibatideEptifibatide ((upstreamupstream))TirofibanTirofiban / / EptifibatideEptifibatide ((upstreamupstream) () (AbciximabAbciximab dopo coro ) STRESS Tdopo coro ) STRESS TESTEST((AbciximabAbciximab dopo coro ) dopo coro ) (+) (+) ((--))

CORO URGENTE CORO URGENTE CORO PRECOCE CORO ELETTIVA TERAPICORO PRECOCE CORO ELETTIVA TERAPIA MEDICAA MEDICA+ PTCA / CABG + PTCA / CABG + PTCA / CABG + PTCA / CABG+ PTCA / CABG + PTCA / CABG

L’evoluzione della gestione del NSTEMI ha

migliorato la Prognosi MA

..nel mondo reale:

•La stratificazione del rischio non sempre

guida la terapia

•La disponibilità detta l’uso della

rivascolarizzazione

•Ampio sottoutilizzo di terapie efficaci spt.

nei soggetti a maggior rischio

Problema attuale

CONCLUSIONI

• La più sicura ed efficace strategia é quella individualizzata,

che integra:

- trattamento anti-trombotico ed anti-ischemico

- precoce stratificazione del rischio individuale, finalizzata alla

scelta dell'ulteriore iter piu' idoneo

• Identificare caratteristiche di rischio “patient-related” e altre

riconducibili alla procedura invasiva, sia per quanto riguarda

la patologia coronarica da trattare che per il rischio

procedurale extra-coronarico

• Stratificato il rischio globale del paziente con SCA-noSTEMI,

all’ingresso e in modo continuativo e dinamico, la strategia

gestionale doserà di conseguenza il livello di aggressività

terapeutica.

CONCLUSIONI

Grazie per l’attenzione!

La variabilità di presentazione clinica della sindrome, le peculiarità logistiche e gestionali locali in termini di risorse allocabili e “facilities” interventistiche rendono comunque anacronistico un approccio diagnostico-terapeutico dogmatico. Al momento, la più sicura ed efficace strategia é quella individualizzata, che integra un sollecito trattamento anti-trombotico ed anti-ischemico ad una precoce stratificazione del rischio individuale, finalizzata alla scelta dell'ulteriore iter piu' idoneo, sia per quanto riguarda la scelta dell’ambiente di cura, che il tipo di monitorizzazione clinica, l'eventuale associazione di altri presidi farmacologici anti-piastrinici ed il ricorso alle procedure invasive ed interventistiche (1).Ai fini di una corretta straitificazione del rischio e di una corretta scelta terapeutica, èbene identificare caratteristiche di rischio a) “patient-related” quali l’età, diabete, storia d scompenso, insufficienza renale, pregresso IM, etc; b) quelle caratteristiche riconducibili alla presentazioneclinica (durata dei sintomi, shock, tipo di modificazioni ECG, positività dei marcatori di danno miocardico); c) altre, infine, riconducibili alla procedura invasiva, sia per quanto riguarda la patologia coronarica da trattare (estensione e severità della coronaropatia, malattia del graft venoso, sede e morfologia angiografica della lesione culprit, presenza di calcificazioni o materiale trombotico) che per il rischio procedurale extra-coronarico (ad es di nefropatia indotta dal mezzo di contrasto).Stratificato il rischio globale del paziente con SCA-noST␣, all’ingresso e in modo continuativo e dinamico, la strategia gestionale doserà di conseguenza il livello di aggressività terapeutica. Valori di “risk score” TIMI >2, PURSUIT >14 o GRACE >133, identificano quei pazienti a maggio rischio a breve e medio-termine, da avviare quanto prima al cateterismo, e nel caso, alla rivascolarizzazione. Nel caso dei pazienti a basso rischio, al contrario, una valutazione di ischemia inducibile con l'opportunità di intervenire subito solo in caso di recidiva resta di fatto l’unica ipotesi terapeutica suffragata da una forte ed inequivocabile evidenza scientifica.

Inizial terapeutic measure

Checklist of tratments when an ACS diagnosisappears likely

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