Invasive evaluation timing in nstemi (1)

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PCI in NSTEMIPCI in NSTEMI

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Case ---Mr BCase ---Mr B

68 yr old68 yr oldHistory of HTN, hyperlipaedimiaHistory of HTN, hyperlipaedimiaOn regular aspirinOn regular aspirinPresented with acute chest pain to one of Presented with acute chest pain to one of peripheral hospitalsperipheral hospitalsST depression in lateral leadsST depression in lateral leadsBP 141/80 and P 86BP 141/80 and P 86Trop T +Trop T +Cr 1.2Cr 1.2

TIMI risk scoreTIMI risk score

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65 yrs or more65 yrs or more3 or more risk factors3 or more risk factorsPrior coronary stenosis more than 50%Prior coronary stenosis more than 50%ST deviation ST deviation Raised enzymesRaised enzymesUse of aspirin in prior 7 daysUse of aspirin in prior 7 days2 or More angina episode in last 24 2 or More angina episode in last 24 hrs hrs

GRACE risk scoreGRACE risk score

55

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GRACE SCOREGRACE SCORE

77

Case ---Mr BCase ---Mr B

TIMI score: 4---TIMI score: 4---20% risk at 14 days of: all-cause 20% risk at 14 days of: all-cause mortality, new or recurrent MI, or severe mortality, new or recurrent MI, or severe recurrent ischemia.recurrent ischemia.

GRACE score: 144---3% in hospital death or 17% GRACE score: 144---3% in hospital death or 17% IH death or MI.IH death or MI.

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WHAT WHAT SHOULD WE SHOULD WE

DO?DO?

992014 ACC/AHA NSTEMI-ACS guideline

ESC 2015ESC 2015

1010

INVASIVE INVASIVE VS VS

CONSERVATIVECONSERVATIVE1111

TIMI IIIBVANQUISH

MATE

INVASIVE STRATEGY are not SUPERIOR

TRIALS of PRE STENT ERA

RECENT TRIALSRECENT TRIALS

FRISC IIFRISC IIICTUSICTUSRITA 3RITA 3TACTICS TIMI 18TACTICS TIMI 18VINOVINO

RCT FOLLOW UP

Time from randomisation to

angio

GPIIb/IIIa use

Stent in Invasive

arm

FRISC II 60 < 7 days( mean 4 days)

10/10 61

ICTUS 36 24-48 hrs 94/75 88

RITA-3 60 <72 hrs, mean 2 days 9/NR 88

TACTICS-TIMI 6 4-48 hrs( 22 hrs) 94/59 83

VINO 6 First day strategy( 6.2 hrs)

0 50

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META analysisMETA analysisFor the index hospital admission there was no significant overall

difference between the invasive and conservative group with

respect to death, stroke or non-fatal MI

However, an invasive strategy significantly decreased the

composite of death and MI at 6-12 months follow-up, both late

(>2 yrs) death and late MI, and reduced thelong-term rate of re-

hospitalisation.

Procedure- related MI Procedure- related MI was significantly increased in the was significantly increased in the

invasive arm invasive arm

There was There was no difference in mortality at any time whether no difference in mortality at any time whether

angiography was undertaken very early angiography was undertaken very early (<24 hours from (<24 hours from

randomisation - ICTUS, TACTICS-randomisation - ICTUS, TACTICS-TIMI TIMI 18, VINO) or when 18, VINO) or when

undertaken later (>48 hours - RITA-3, FRISC-II).undertaken later (>48 hours - RITA-3, FRISC-II).

CONTD……………..

Trials not involving the routine use of GPIIbIIIa inhibitors (VINO, RITA-

3, FRISC-II) an invasive strategy significantly decreased intermediate (6-

12 months) MI and refractory angina, but not death at any time point, nor

the index admission MI.

CONTD……………..

CONTD…….CONTD…….

Trials with the routine use of GPIs (mainly based on TACTICS-TIMI 18 but Trials with the routine use of GPIs (mainly based on TACTICS-TIMI 18 but

including ICTUS - use of GPIs was 94% in the invasive arms of both trials) an including ICTUS - use of GPIs was 94% in the invasive arms of both trials) an

invasive strategy significantly invasive strategy significantly reduced in-hospital non-fatal MI, the composite of reduced in-hospital non-fatal MI, the composite of

death or non-fatal MI (but not death alone), death or non-fatal MI (but not death alone), suggesting that appropriate use of GPIs suggesting that appropriate use of GPIs

reduces in-hospital MI reduces in-hospital MI when added to an invasive strategy. It also reduced when added to an invasive strategy. It also reduced

rehospitalisation over 6-12 months follow-uprehospitalisation over 6-12 months follow-up

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CONTD…………CONTD…………

In the RITA-3 trial there was no difference between management strategies for In the RITA-3 trial there was no difference between management strategies for

those at lowest risk, but those those at lowest risk, but those at highest risk at highest risk who were managed by an early who were managed by an early

invasive strategy had a significantly reduced risk of death or MIup to 5 years invasive strategy had a significantly reduced risk of death or MIup to 5 years

follow-up.follow-up.

In the FRISC-II trial, an invasive strategy significantly reduced the

composite of death or non-fatal MI in those with either ST depression or

troponin elevation (higher risk), but not in those without (lower risk),

suggesting that the benefit of an invasive strategy was mostly in higher risk

people.

CONTD…….CONTD…….In TACTICS TIMI trial benefit is confined to higher risk In TACTICS TIMI trial benefit is confined to higher risk

patientspatients

Quality of life outcomes are better in early invasive Quality of life outcomes are better in early invasive

group( FRISC II & RITA 3)group( FRISC II & RITA 3)

2121

in the in the ICTUSICTUS trial an early invasive strategy trial an early invasive strategy did not did not confer benefit confer benefit

and there was no evidence that treatment effect was influenced and there was no evidence that treatment effect was influenced

by risk at randomization. Interpretation of the ICTUS trial is by risk at randomization. Interpretation of the ICTUS trial is

influenced by a high rate of early angiography and influenced by a high rate of early angiography and

revascularization in the conservative arm of the trialrevascularization in the conservative arm of the trial

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INVASIVE STRATEGYINVASIVE STRATEGYHOW MUCH EARLY IT HOW MUCH EARLY IT

SHOULD BE?SHOULD BE?

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RCTs ---Timing of invasive evaluationRCTs ---Timing of invasive evaluationIn Pts with NSTEMIIn Pts with NSTEMI

TrialTrial Yr of Yr of enrolmenenrolmentt

No of PtsNo of Pts ScoringScoring Timing Timing (hours)(hours)

11 ISAR-ISAR-COOLCOOL

2000-022000-02 410410 Positive enzyme Positive enzyme or ST depression or ST depression >1mm>1mm

2.4 Vs 862.4 Vs 86

22 ABOARDABOARD 2006-082006-08 352352 TIMI>3TIMI>3 1.2 Vs 21 1.2 Vs 21

33 TIMACSTIMACS 2003-082003-08 30313031 GRACEGRACE 14 Vs 50 14 Vs 50

44 LIPSIA LIPSIA NSTEMINSTEMI

2006-2006-20102010

602602 GRACEGRACE 2 vs 10-2 vs 10-4848

TIMACS trial TIMACS trial 14 hr Vs 52 hr14 hr Vs 52 hr

Early versus Delayed Invasive Early versus Delayed Invasive InterventionIntervention

in Acute Coronary Syndromesin Acute Coronary Syndromes

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TIMACS trial TIMACS trial N Engl J Med 2009;360:2165-N Engl J Med 2009;360:2165-

75.75.3031 ACS patients3031 ACS patients

Early (≤24 hours) Vs delayed intervention (≥36 Early (≤24 hours) Vs delayed intervention (≥36 hours).hours).

Primary outcome: a composite of death, MI, or Primary outcome: a composite of death, MI, or stroke at 6 m. stroke at 6 m.

Secondary outcome: death, MI, or refractory Secondary outcome: death, MI, or refractory ischemia at 6 mischemia at 6 m

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..

TIMACS trial May 2009TIMACS trial May 2009N Engl J Med 2009;360:2165-75N Engl J Med 2009;360:2165-75

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TIMACS trial May 2009TIMACS trial May 2009N Engl J Med 2009;360:2165-75.N Engl J Med 2009;360:2165-75.

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ISAR-COOL trialISAR-COOL trial2.4hr Vs 86hr2.4hr Vs 86hr

JAMA, September 24, 2003—Vol 290, No. 12 JAMA, September 24, 2003—Vol 290, No. 12 15931593

IntracoronaryIntracoronaryStenting With AntithromboticStenting With Antithrombotic

Regimen Cooling-Off trialRegimen Cooling-Off trial

3131

ISAR-COOL trialISAR-COOL trialJAMA, September 24, 2003—Vol 290, No. 12 JAMA, September 24, 2003—Vol 290, No. 12 15931593

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3333


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ABOARD trialABOARD trial1.2hr Vs 21hr1.2hr Vs 21hr

JAMA, September 2, 2009—Vol 302, No. 9 JAMA, September 2, 2009—Vol 302, No. 9 949949

The The AAngioplasty to ngioplasty to BBlunt the Rise oflunt the Rise ofTrTrooponin in ponin in AAcute Coronary Syndromescute Coronary Syndromes

RRandomized for an Immediateandomized for an Immediateor or DDelayed Intervention (ABOARD)elayed Intervention (ABOARD)

TrialTrial

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ABOARD trialABOARD trialJAMA, September 2, 2009—Vol 302, No. 9 JAMA, September 2, 2009—Vol 302, No. 9 949949

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ABOARD trialABOARD trialJAMA, September 2, 2009—Vol 302, No. 9 JAMA, September 2, 2009—Vol 302, No. 9 949949

LLeipzig eipzig IImmediate versus earlymmediate versus early and late and late PPercutaneouercutaneouSS coronary coronary

IInterventionntervention tritriAAl in NSTEMI (LIPSIA-NSTEMI l in NSTEMI (LIPSIA-NSTEMI

Trial)Trial)

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602 patients602 patientsImmediate invasive( <2 hr)Immediate invasive( <2 hr)Early invasive( 10- 48 hr)Early invasive( 10- 48 hr)selectiveselective

Primary OutcomePrimary OutcomePeak CK-MB activityPeak CK-MB activityArea under curve of CK MB releaseArea under curve of CK MB release

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Not Different

Secondary OutcomeSecondary Outcome

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A meta-analysis of randomized trials addressing the optimal timing (early vs. delayed) of coronary

angiography in NSTE-ACS.

(ELISA, ABOARD, ISAR-COOL, TIMACS)

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From the meta-analysis

DRUGS TO BE DRUGS TO BE USEDUSED

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ANTIPLATELET ANTIPLATELET REGIMENREGIMEN

CONTD…………..CONTD…………..

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CONTD……..CONTD……..

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UPSTREAM GPIIb/IIIa – should we UPSTREAM GPIIb/IIIa – should we use?use?

EARLY ACSEARLY ACSACUITY timing trialACUITY timing trial

- NEGATIVE - NEGATIVE TRIALTRIAL

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Anticoagulant StrategyAnticoagulant Strategy

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Contd………….Contd………….

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Bivaluridin is It better?Bivaluridin is It better?ACUITY trialACUITY trial

Three arm UFH/LMWH+ GPIIb/IIIaThree arm UFH/LMWH+ GPIIb/IIIa Bivaluridin+ GPIIb/IIIaBivaluridin+ GPIIb/IIIa BivaluridinBivaluridinIntermediate to high risk patients Intermediate to high risk patients

planned for PCIplanned for PCIPrimary composite ischemic endpoint Primary composite ischemic endpoint

are same but less major bleedingare same but less major bleeding

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CONTD…….CONTD…….

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Is there any problem with Is there any problem with FONDAPARINUXFONDAPARINUX

OASIS-5 trialOASIS-5 trialFondaparinux vs EnoxaparinFondaparinux vs EnoxaparinPrimary composite ischemic end point Primary composite ischemic end point

are similarare similarMajor bleeding less Major bleeding less

Increased catheter Increased catheter thrombosisthrombosis

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Anticoagulant regimen during Anticoagulant regimen during PCIPCI

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PCIPCI

5757

CABGCABG

5858

ESC 2015 what is newESC 2015 what is new

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Take home messageTake home messageUnstable pts should have urgent cath Unstable pts should have urgent cath lab study +/- revascularizationlab study +/- revascularization

High risk pts should ideally have cath High risk pts should ideally have cath study +/- revascularization in 24hrsstudy +/- revascularization in 24hrs

Low - intermediate risk pt should Low - intermediate risk pt should have stress test to document have stress test to document ischaemiaischaemia

Invasive evaluation timing in nstemi (1)

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