Revascularization in Patiens with ACS without ST segment elevation … · 2017-07-13 ·...

Revascularization in Patientswith ACS without ST segment

elevation

Cardiovascular UpdateCardiovascular UpdateRotterdam, June 11Rotterdam, June 11thth, 2012, 2012

AMC Amsterdam Interventional CardiologyAMC Amsterdam Interventional Cardiology

Robbert J de Winter MD PhD FESC

Professor Clinical CardiologyAcademic Medical CenterUniversity of Amsterdam

ACUTE CORONARY SYNDROMEACUTE CORONARY SYNDROME

No ST ElevationNo ST Elevation ST ElevationST Elevation

ACC/AHA guidelines ACC/AHA guidelines UA/NSTEMI 9/00

Acute Coronary SyndromeAcute Coronary Syndrome

Davies MJ Davies MJ

Heart 83:361, 2000Heart 83:361, 2000

Ischemic DiscomfortIschemic DiscomfortPresentationPresentation

Working DxWorking Dx

Hamm Lancet 358:1533,2001Hamm Lancet 358:1533,2001


Unstable AnginaUnstable Angina NQMI QwMIMyocardial InfarctionNQMI QwMI

Myocardial Infarction

NSTEMINSTEMI

No ST ElevationNo ST Elevation ST ElevationST Elevation

Unstable AnginaUnstable Angina NQMINQMI QwQw MIMI

NSTEMINSTEMI

Myocardial InfarctionMyocardial Infarction

ECGECG

BiochemBiochem. .

MarkerMarker

Final DxFinal Dx

Revascularization in STEMI / NSTEMI

♥ When there is a clinical diagnosis of

thrombotic coronary artery occlusion,

immediate angiography and mechanical

reperfusion therapy is recommended


reperfusion therapy is recommended

and has been shown to reduce

mortality

♥ For NSTEMI / UA this is less clear

♥ Revascularization to improve prognosis

♥ Revascularization to relieve symptoms

Revascularization in nSTE-ACS 2012


♥ Revascularization as part of a

comprehensive strategy in nSTE-ACS

Revascularization in nSTE-ACS

Patients with nSTE-ACS represent a very heterogeneous

population:

♥ 45-year old male, positive family history, new onset

chest pain early morning, symmetrical negative T-


waves anterior ECG leads, normal troponin

♥ 80-year old lady with hypertension, diabetes, mitral

regurgitation, paroxysmal atrial fibrillation, LBBB,

progressive chest pain on exertion, presenting with

elevated troponin

Acute coronary syndromes

Non-ST-elevation ACS is often a combination of

hemodynamically significant lesion, plaque

rupture, thrombus formation, coronary spasm

and increased oxygen demand, but with


preserved flow

Medical treatment combination of anti-ischemic,

vaso-dilator, anti-platelet and anti-coagulant

drugs

AMCAMC--UVA Amsterdam Interventional CardiologyUVA Amsterdam Interventional Cardiology

Risk of ischemic events according to the GRACE risk score


Meta-analysis non-STE-ACS

Mehta et al. JAMA 2005;293:2908-17

FRISC II: 5-year mortality

RR 0.95 (95%CI: 0.75-1.21, p=0.693)

0 1 2 3 4 5

Selective invasive

Routine invasive(Minimal 5-Y FU)

RITA-3: 5-year mortality

Selective invasive

OR 0.76 (95%CI: 0.58-1.00, p=0.054)

Routine invasive

(Median 5-Y FU)

ICTUS: 5-year mortality

Routine invasive

HR 1.13 (95%CI: 0.80-1.60, p=0.52)

Selective invasive

Damman P. et al.

(Minimal 5-Y FU)

LongLong--Term Outcome of a Routine versus Term Outcome of a Routine versus Selective Invasive Strategy in Patients with Selective Invasive Strategy in Patients with

nonnon--ST elevation ACS ST elevation ACS

Keith AA Fox, Tim C Clayton, Peter Damman, Keith AA Fox, Tim C Clayton, Peter Damman, Stuart J Pocock, Robbert J de Winter, Jan GP Tijssen, Stuart J Pocock, Robbert J de Winter, Jan GP Tijssen, Stuart J Pocock, Robbert J de Winter, Jan GP Tijssen, Stuart J Pocock, Robbert J de Winter, Jan GP Tijssen,

Bo Lagerqvist, Lars WallentinBo Lagerqvist, Lars Wallentin

FIRFIR collaboration: collaboration: FFRISC RISC IICTUS CTUS RRITAITA

FIR patientFIR patient--pooled databasepooled database

• Core variables:• Demographics• Clinical history• Risk factors for CAD• Baseline ECG characteristics• Baseline laboratory results• Baseline laboratory results• 5-year clinical outcomes

• 5467 patients with nSTE-ACS included

FIRFIR collaboration: collaboration: FFRISC RISC IICTUS CTUS RRITAITA

Timing of first coronary revascularizationTiming of first coronary revascularization

60

80

100C

um

ula

tive p

erc

enta

ge

Selective invasive

Routine invasive

64.1%64.1% 71.8%71.8% 73.3%73.3%

17.6%17.6% 41.6%41.6% 47.8%47.8%

0

20

40

Cum

ula

tive p

erc

enta

ge

0 1 2 3 4 5

Follow-up time (years)

17.6%17.6% 41.6%41.6% 47.8%47.8%

Revasc at 1yr % Routine invasiveRoutine invasive Selective invasiveSelective invasive

ICTUS 7979 5454

FRISC II 7878 4444

RITA-3 5757 2828

Table 2: Outcomes by study and treatment

Combined dataset Hazard ratio p-value

Selective Selective invasive invasive n = 2746n = 2746

Routine Routine invasive invasive n = 2721n = 2721

(95% CI)

MI 338 338 260 260 0.77 0.001

Primary outcomes at 5 yearsPrimary outcomes at 5 years

MI 338 338 12.9%12.9%

260 260 10.0%10.0%

0.77 (0.65 - 0.90)

0.001

CV death 218 218 8.1%8.1%

181 181 6.8%6.8%

0.83 (0.68 - 1.01)

0.068

CV death/MI

475 475 17.9%17.9%

389 389 14.7%14.7%

0.81 (0.71 -0.93)

0.002

Table 2: Outcomes by study and treatment

Combined dataset Hazard ratio p-value

Selective Selective invasiveinvasive

Routine Routine invasiveinvasive

(95% CI)

All-cause 321 321 288 288 0.90 0.19

Outcomes at 5 yearsOutcomes at 5 years

All-cause death

321 321 11.7%11.7%

288 288 10.6%10.6%

0.90 (0.77 -1.05)

0.19

All-cause death/MI

560 560 20.9%20.9%

480 480 18.1%18.1%

0.85 (0.75 - 0.96)

0.008

Cumulative risk of CV death or MICumulative risk of CV death or MI

10

15

20

25C

um

ula

tive p

erc

enta

ge

Selective invasive

Routine invasive 17.9%17.9%

14.7%14.7%

0

5

Cum

ula

tive p

erc

enta

ge

2721 2485 2410 2235 2166 1952RI

2746 2452 2351 2178 2077 1880SI

0 1 2 3 4 5


HR 0.81 95% CI 0.71HR 0.81 95% CI 0.71--0.930.93p = 0.002p = 0.002

Are the results influenced by the baseline risk of Are the results influenced by the baseline risk of

the patients?the patients?

• Univariable and multivariable predictors

of outcome derived (Cox regression).

p<0.01 for inclusion in multivariable

model (Wald test)

• Simplified integer score derived:• Simplified integer score derived:

• Age, diabetes, prior MI, ST depression, hypertension, BMI

Cumulative risk of CV death or MI by risk groupCumulative risk of CV death or MI by risk group

20

30

40

50C

um

ula

tive

pe

rce

nta

ge

Selective invasive

Routine invasive

Intermediate

0

10

20

Cu

mu

lative

pe

rce

nta

ge

2721 2485 2410 2235 2166 1952RI 2746 2452 2351 2178 2077 1880SI

0 1 2 3 4 5


Intermediate

Low

Cumulative risk of CV death or MI by risk groupCumulative risk of CV death or MI by risk group

20

30

40

50C

um

ula

tive

pe

rce

nta

ge

Selective invasive

Routine invasiveHigh

Intermediate

0

10

20

Cu

mu

lative

pe

rce

nta

ge

2721 2485 2410 2235 2166 1952RI

2746 2452 2351 2178 2077 1880SI

0 1 2 3 4 5


Intermediate

Low

Summary

• The routine invasive strategy reduced

cardiovascular death or MI at long-term follow-up

• 3.2% absolute risk reduction in CV death/MI

• 19% relative risk reduction

• No statistically significant reduction in mortality• No statistically significant reduction in mortality

• Risk stratification identifies the patient group with

the greatest absolute benefits

• 11.1% absolute risk reduction in highest risk patients

KAA Fox, TC Clayton, P Damman, SJ Pocock, RJ de Winter, JGP Tijssen,

B Lagerqvist, L Wallentin (FIR collaboration) JACC 2010;55:2435-45

< 72 hrs


< 24 hrs

< 24 hrs


< 72 hrs

An International Randomized Trial of Early

TIMACSTiming of Interventionin patients with Acute Coronary Syndromes

An International Randomized Trial of Early

Versus Delayed Invasive Strategies in

Patients with Non-ST Segment Elevation

Acute Coronary Syndromes

Funded by Canadian Institutes of Health ResearchFunded by Canadian Institutes of Health Research

Additional support from GSK and SanofiAdditional support from GSK and Sanofi--AventisAventis

Preliminary Results

TIMACSTIMACSTIMACSTIMACS Interventions and TimingInterventions and Timing

EarlyEarly

N=1,593N=1,593

DelayedDelayed

N=1,438N=1,438

Coronary Angiography (%)Coronary Angiography (%) 97.697.6 95.595.5

Median time (h Median time (h ±± iqriqr)) 14 (314 (3--21)21) 50 (4150 (41--81)81)

Preliminary Results as of Nov 7, 2008


PCI (%)PCI (%) 59.659.6 55.055.0


CABG (%)CABG (%) 14.714.7 13.613.6

Median time (d Median time (d ±± iqriqr)) 7.7 (4.77.7 (4.7--17.4)17.4) 10.8 (6.710.8 (6.7--19.8)19.8)

iqr=interquartile range

TIMACSTIMACSTIMACSTIMACS

Primary OutcomePrimary OutcomeDeath, MI, or StrokeDeath, MI, or Stroke

Cu

mu

lative

Ha

za

rd

0.0

60

.10

Death/MI/Stroke at 180 days

Early

Delayed

HR 0.85


Days

Cu

mu

lative

Ha

za

rd

0.0

0.0

2

0 30 60 90 120 150 180

No. at Risk

Delayed

Early

1438 1328 1269 1254 1234 1229 1211

1593 1484 1413 1398 1391 1382 1363

HR 0.8595% CI 0.68-1.06

P= 0.15

TIMACSTIMACSTIMACSTIMACS

Secondary OutcomeSecondary OutcomeDeath, MI, or Refractory IschemiaDeath, MI, or Refractory Ischemia

Cum

ula

tive H

azard

0.0

80.1

2

Death/MI/RI at 180 days

Delayed

Early


Days

Cum

ula

tive H

azard

0.0

0.0

4

0 30 60 90 120 150 180

No. at Risk

Delayed

Early

1438 1303 1243 1230 1209 1205 1187

1593 1485 1417 1402 1394 1386 1366

HR 0.7295% CI 0.58-0.79

P=0.002

TIMACSTIMACSTIMACSTIMACSPrePre--specified Subgroupsspecified Subgroups

Overall

Age < 65

>=65

FemaleMale

3031

1293

1736

10521976

9.7

6.5

12.3

9.79.8

0.463

0.540

0.85 ( 0.68 - 1.06 )

0.98 ( 0.64 - 1.52 )

0.83 ( 0.64 - 1.07 )

0.77 ( 0.54 - 1.12 )

0.89 ( 0.68 - 1.18 )

NCharacteristic HR (95% CI) Interaction p-Value

Early%

11.4

6.5

14.8

12.310.9

Delayed%

Male

No ST deviationST deviation

No elevated marker

Elevated marker

GRACE 0-140

GRACE >=141

1976

15231508

668

2363

2070

961

9.8

7.611.7

10.5

9.5

7.7

14.1

0.540

0.722

0.423

0.0097

0.89 ( 0.68 - 1.18 )

0.88 ( 0.62 - 1.26 )

0.81 ( 0.61 - 1.07 )

1.00 ( 0.62 - 1.60 )

0.81 ( 0.63 - 1.04 )

1.14 ( 0.82 - 1.58 )

0.65 ( 0.48 - 0.88 )

0.33 0.5 0.7 1.00 1.52.0 3.0

Early better Delayed better Hazard Ratio (95% CI)

10.9

8.714.3

10.5

11.7

6.7

21.6

TIMACSTIMACSTIMACSTIMACSConclusionsConclusions

1. Overall, we found no significant difference between an early and a delayed invasive strategy for prevention of death, MI or stroke (primary outcome).

2. In the subgroup at highest risk (GRACE score > 140), an early invasive strategy appears to be superior to a


an early invasive strategy appears to be superior to a delayed invasive strategy for prevention of death, MI or stroke.

3. The early invasive strategy had a large impact on reducing the rate of refractory ischemia by 70%.

4. There were no significant differences in major bleeding or other safety concerns between the two strategies.

ABOARD study designABOARD study designABOARD study designABOARD study design

NSTENSTE--ACS ACS 2 of 3 Criteria: Ischemic symptom, ST2 of 3 Criteria: Ischemic symptom, ST--T change, troponin riseT change, troponin rise

with TIMI score with TIMI score >> 33

IVRS RANDOMIZATIONIVRS RANDOMIZATION

Preliminary Results

Immediate cathImmediate cath Next day cathNext day cath

All PCIs on abciximabAll PCIs on abciximab

11--month Followmonth Follow--upup

OutcomesOutcomesOutcomesOutcomes

•• Primary Primary

−− MI: defined as the peak of troponin I during MI: defined as the peak of troponin I during hospitalizationhospitalization

•• SecondarySecondary

Preliminary Results

•• SecondarySecondary

1.1. Death (any), new MI (CKDeath (any), new MI (CK--MB) or urgent MB) or urgent revascularization (PCI or CABG)revascularization (PCI or CABG)

2.2. Death, new MI, urgent revascularization or Death, new MI, urgent revascularization or recurrent ischemia recurrent ischemia

3.3. Individual parametersIndividual parameters

Index ACS eventIndex ACS eventIndex ACS eventIndex ACS event

Entry criteria, (%) Immediate(N=175)

Delayed(N=177)

Ischemic symptom 98.2 97.7

ST-T segment changes 69.7 76.8

Preliminary Results

ST-T segment changes 69.7 76.8

Elevated Troponin I 75.4 72.9

TIMI score, (%)

> 3 95.4 95.5

> 5 22.9 30.5

InIn--hospital medicationshospital medicationsInIn--hospital medicationshospital medications

Immediate(N=175)

Delayed(N=177)

Aspirin, (%) 99.4 100

Clopidogrel, (%) 96.6 98.9

Loading dose, mean ± sd, mg 660 ± 268 663 ± 267

Maintenance dose, mean ± sd, mg 111 ± 40 111 ± 39

Abciximab, (%) 65.1 57.4

Preliminary Results

Abciximab, (%) 65.1 57.4

Unfractionated heparin only, (%) 5.1 3.4

Low Molecular Weight Heparin only, (%) 68.6 67.2

Both UFH and LMWH, (%) 22.9 28.8

Neither UFH nor LMWH, (%) 2.9 0.6

Beta-blocker, (%) 87.4 85.3

Statin, (%) 94.3 95.5

ACE inhibitor or ARB, (%) 84.5 80.2

Time to catheterization (hrs)Time to catheterization (hrs)Time to catheterization (hrs)Time to catheterization (hrs)

IMMEDIATEIMMEDIATE DELAYEDDELAYED

FRISC 2 (1999) 96 408

TRUCS (2000) 48 120

TIMI-18 (2001) 22 79

VINO (2002) 6 1464

Preliminary Results

VINO (2002) 6 1464

RITA 3 (2002) 48 1020

ELISA (2003) 6 50

ISAR-COOL (2003) 3 86

ICTUS (2005) 23 283

TIME-ACS (2008) 14 50

ABOARD (2009)

median (IQR), hr.min1.10

(0.51-2.03)20.48

(17.30-24.36)

InterventionsInterventionsInterventionsInterventions

IMMEDIATEIMMEDIATE DELAYEDDELAYED

Radial access (%) 87.487.4 81.881.8

Culprit artery

Left main trunk, (%) 4.1 7.3

Left anterior descending artery, (%) 48.6 45.0

Circumflex artery, (%) 24.7 29.1

Preliminary Results

Circumflex artery, (%) 24.7 29.1

Right coronary artery, (%) 24.7 25.2

Coronary bypass graft, (%) 2.1 2.0

Percutaneous Coronary Intervention, (%) 80.1 69.5

Stent (at least one), (% of PCI) 94.0 96.2

DES (at least one), (% of PCI) 47.9 55.2

Number of stents/patient, mean±sd 1.2 ± 0.9 1.2 ± 1.0

CABG surgery, (%) 11.0 11.3

Primary EP (peak of troponin I)Primary EP (peak of troponin I)Primary EP (peak of troponin I)Primary EP (peak of troponin I)

0.0

80.1

00.1

20.1

4

Density

Distribution curves of the peaks values of troponin in the immediate and delayed groups

immediate groupdelayed group

Median, IQR

2.1 (0.3-7.1)1.7 (0.3-7.2)

Peak values of troponin I in the 2 groups

p = 0.70

Preliminary Results

0 20 40 60 80 100

0.0

00.0

20.0

40.0

60.0

8

Troponin I (ng/mL)

Density

Composite Ischemic Endpoints at 1 monthComposite Ischemic Endpoints at 1 month

%%

15

20

25

Immediate

Delayed

P=0.31

P=0.94

Preliminary Results

0

5

10

Death / MI / UR Death / MI / UR / RIKey secondary EP

Individual Ischemic Endpoints at 1 monthIndividual Ischemic Endpoints at 1 month

8

10

12

14

16

18

20

ImmediateDelayed

%%

P=0.09

P=0.32

P=0.08

Preliminary Results

0

2

4

6

8

Dea

th

MI

Urg

Rev

asc

Urg

PC

IU

rg C

AB

GR

ec Is

ch

P=0.28

P=0.32

P=0.57

P=0.62

Safety outcomes at 1 monthSafety outcomes at 1 monthSafety outcomes at 1 monthSafety outcomes at 1 month

Immediate Delayed PP

Major bleeding at 1 month, (%)Major bleeding at 1 month, (%) 4.0 6.8 0.250.25

NonNon--CABG related major bleeding, CABG related major bleeding, 2.3 5.1 0.260.26

CABGCABG--related major bleedingrelated major bleeding 1.7 1.7 1.001.00

Preliminary Results

Transfusion Transfusion >> 2 units2 units 3.4 5.6 0.320.32

Transfusion Transfusion >> 5 units5 units 1.1 1.1 1.001.00

Thrombocytopenia at 1 month, (%)Thrombocytopenia at 1 month, (%) 2.9 4.5 0.410.41

NonNon--CABG CABG thrombocytopenia,thrombocytopenia, (%)(%) 2.3 4.0 0.540.54

PostPost--CABG CABG thrombocytopenia,thrombocytopenia, (%)(%) 0.6 0.6 1.001.00

Sites of Major BleedingsSites of Major BleedingsSites of Major BleedingsSites of Major Bleedings

11-- GastroGastro--IntestinalIntestinal 44

22-- PuncturePuncture--relatedrelated 44

33-- HemopericardiumHemopericardium 22

n

Preliminary Results

33-- HemopericardiumHemopericardium 22

44-- IntracranialIntracranial 11

55-- EpistaxisEpistaxis 11

66-- Hematoma (not punctureHematoma (not puncture--related)related) 11

unknownunknown 77

One patient had 2 bleeding events

Subgroup analysis (primary EP)Subgroup analysis (primary EP)Subgroup analysis (primary EP)Subgroup analysis (primary EP)

Median differences and Hodges-Lehmann CI for the primary end point (peak of troponin)

Preliminary Results

Immediate better Delayed better

Hospital stayHospital stayHospital stayHospital stay

ImmediateImmediate

Median, IQR, hrsMedian, IQR, hrs

55( 30; 98)

Preliminary Results

Median, IQR, hrsMedian, IQR, hrs ( 30; 98)

DelayedDelayed

Median, IQR, hrsMedian, IQR, hrs

77( 49; 145)

P<0.001

ConclusionsConclusionsConclusionsConclusions

A « A « primaryprimary PCI PCI strategystrategy » in NSTE» in NSTE--ACS ACS

((comparedcompared withwith a a rapidrapid intervention on the intervention on the nextnext

dayday):):

−− isis feasiblefeasible, but , but doesdoes not not reducereduce the the riskrisk of MI (of MI (primaryprimary

Preliminary Results

−− isis feasiblefeasible, but , but doesdoes not not reducereduce the the riskrisk of MI (of MI (primaryprimary

outcomeoutcome))

−− isis not not associatedassociated withwith significantsignificant differencesdifferences in in otherother

efficacyefficacy or or safetysafety outcomesoutcomes

−− doesdoes not not benefitbenefit to a to a particularparticular subgroupsubgroup of patientsof patients

−− shortensshortens significantlysignificantly hospitalhospital staystay

A Death B Myocardial infarction

C Major bleeding D Recurrent Ischemia

AMCAMC--UVA Amsterdam Interventional CardiologyUVA Amsterdam Interventional CardiologyKatritsis et al. EurHJ 2011;32:32-40

C Major bleeding D Recurrent Ischemia

Medical management vs Revascularization

AMCAMC--UVA Amsterdam Interventional CardiologyUVA Amsterdam Interventional CardiologyChan et al. JACC Int 2008;1:369-78


SYNERGY

AMCAMC--UVA Amsterdam Interventional CardiologyUVA Amsterdam Interventional CardiologyChan et al. JACC Int 2008;1:369-78

Predictors of early invasive management

CRUSADE

AMCAMC--UVA Amsterdam Interventional CardiologyUVA Amsterdam Interventional CardiologyBhat DL et al. JAMA 2004;292:2096

♥ Post hoc analyses SYNERGY / CRUSADE

♥ Patients magaged medically after angiography constitute a particularly high risk group of patients



♥ We need better strategies to improve

outcome in these patients

nSTE-ACS

What’sComing?

"The secret to creativity is knowing how to hide your sources."

ASA ASA + Clopidogrel

ASA + Prasugrel

-22%Ischaemic

Antiplatelet therapy in ACSThe risk of bleeding

-20%

-19%

+60% +38% +32%

Ischaemic events

Bleeding??!!

hsTnT


Mills et al, JAMA 2011Mills et al, JAMA 2011


TwerenboldTwerenbold et al, et al, EurEur H J 2012H J 2012

< 24 hrs

?


< 72 hrs

Prasugrel / TicagrelorRivaroxaban / Vorapaxar

Darapladip

hs-troponinNew DES

Radial approachRadial approach

"The only thing that interferes with my learning is my education."

Conclusion

Repeat allRCTs

"The only thing that interferes with my learning is my education."

25

30

35

40

25000

30000

35000

40000

45000

PCI ‘s / year # PCI Centers

Number of PCI’s procedures and PCI-centers in the Netherlands

28

+ 13.000 procedures


Source: BHN Nederland

0

5

10

15

20

0

5000

10000

15000

20000

25000

2002 2003 2004 2005 2006 2007 2008 2009 2010

14

♥ Invasive strategy after risk stratification

√ most patients

♥ Reduction in death or MI

√ mortality reduction modest

Revascularization in nSTE-ACS 2012

♥ Reduction length of stay

♥ Improvements in pharmacology & stents &

hs-Troponins

√ has not been tested


Thank YouThank You

Gender and revascularization in nSTE-ACS

AMC Amsterdam Interventional CardiologyAMC Amsterdam Interventional CardiologyO’Donoghue et al. JAMA. 2008 Jul 2;300(1):71-80

Prognosis after procedure related MI


Damman et al. Circulation. 2012;125:568-576

Age and revascularization in nSTE-ACS

CV death or MI


Damman et al. Heart 2012;98:207-213


CV death




Myocardial infarction



Revascularization in Patiens with ACS without ST segment elevation … · 2017-07-13 ·...

Documents

Transcript of Revascularization in Patiens with ACS without ST segment elevation … · 2017-07-13 ·...