Treatment strategies for Treatment strategies for “stable” CAD patients:“stable” CAD patients:

COURAGE, OAT, SWISSI II, COURAGE, OAT, SWISSI II, VIAMI in perspectiveVIAMI in perspective

Pierfrancesco Agostoni, MDPierfrancesco Agostoni, MD

Antwerp Cardiovascular Institute Antwerp Cardiovascular Institute MiddelheimMiddelheim

Department of Interventional CardiologyDepartment of Interventional Cardiology

CClinical linical OOutcomes utcomes UUtilizingtilizingRRevascularization Andevascularization And

AAggressive Druggressive DruGG EEvaluationvaluation

To determine whether To determine whether PCI plus optimal medical PCI plus optimal medical therapytherapy (OMT) reduces the risk of death or nonfatal (OMT) reduces the risk of death or nonfatal

MI in symptomatic patients with stable CAD, as MI in symptomatic patients with stable CAD, as compared with compared with OMT aloneOMT alone. .

Patients with stable angina (CCS I-III or initial CCS Patients with stable angina (CCS I-III or initial CCS IV medically stabilized) IV medically stabilized) ALLALL underwent coronary underwent coronary

angiography and where then randomized toangiography and where then randomized toPCI + OMTPCI + OMT vs. vs. OMTOMT alone alone

Primary OutcomePrimary OutcomeDeath or Nonfatal MIDeath or Nonfatal MI

• 1, 2, or 3 vessel disease (> 80% visual stenosis of 1, 2, or 3 vessel disease (> 80% visual stenosis of proximal coronary segment)proximal coronary segment)

• Anatomy suitable for PCI (not better specified…)Anatomy suitable for PCI (not better specified…)• CCS Class I-III anginaCCS Class I-III angina• Objective evidence of ischemia at baselineObjective evidence of ischemia at baseline• ACC/AHA Class I or II indication for PCIACC/AHA Class I or II indication for PCI

• Uncontrolled unstable angina / CCS IV on therapyUncontrolled unstable angina / CCS IV on therapy• Complicated post-MI courseComplicated post-MI course• Revascularization within 6 monthsRevascularization within 6 months• Ejection fraction <30%Ejection fraction <30%• Cardiogenic shock/severe heart failureCardiogenic shock/severe heart failure• Markedly positive stress test (ST changes at 1° stage)Markedly positive stress test (ST changes at 1° stage)• Significant unprotected LM disease Significant unprotected LM disease

Inclusion CriteriaInclusion Criteria

Exclusion CriteriaExclusion Criteria

50 hospitals (USA and Canada)

2,287 patients enrolled between

6/99-1/04

6% of screened

Total: 2276 vessels diseased… thus lesions…Only 1688 (74%) were attempted in the trial…Despite 60% were 2- or 3VD, 60% received

only 1 stent, while only 40% received >1 stent

At a median f.u. time of 4.6 years…At a median f.u. time of 4.6 years…

But… But… if we look at quality of life…if we look at quality of life…

Is this a “transient” reduction??Is this a “transient” reduction??

and effectively

performed

OOccluded ccluded AArtery rtery TTrialrial

To evaluate outcomes of percutaneous coronary To evaluate outcomes of percutaneous coronary intervention (PCI) versus medical therapy among intervention (PCI) versus medical therapy among

stablestable, , high-riskhigh-risk, , asymptomaticasymptomatic patients with patients with persistent total occlusion of the infarct-related artery persistent total occlusion of the infarct-related artery

post-myocardial infarction (MI).post-myocardial infarction (MI).

Patients presenting late post-MI Patients presenting late post-MI ALLALL underwent underwent angiography from >24 hours to 28 days post-MI and angiography from >24 hours to 28 days post-MI and

were randomized to were randomized to PCI of the IRA + optimal PCI of the IRA + optimal medical therapymedical therapy or or conservative medical therapyconservative medical therapy

Primary OutcomePrimary OutcomeDeath / Nonfatal MI / NYHA IV HFDeath / Nonfatal MI / NYHA IV HF

Inclusion CriteriaInclusion Criteria

Exclusion CriteriaExclusion Criteria

• total occlusion of the infarct-related artery with poor total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow 0 or 1)or absent antegrade flow (TIMI flow 0 or 1)

• increased risk, defined as ejection fraction <50%, increased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with proximal occlusion of a major epicardial vessel with a large risk region, or botha large risk region, or both

• NYHA class III-IV heart failure or caridogenic shockNYHA class III-IV heart failure or caridogenic shock• serum creatinine concentration >2.5 mg/dlserum creatinine concentration >2.5 mg/dl• significant LM or 3-V coronary artery diseasesignificant LM or 3-V coronary artery disease• angina at restangina at rest• severe ischemia on stress testingsevere ischemia on stress testing

ST depression >2 mm

No completion of stage 1

Reversible perfusion defectsin multiple territories

Decreased wall motion in >2 segments on echo

Enrolled to screened ratio?

• Additional PCI in non-IRA vessels: 6-7%Additional PCI in non-IRA vessels: 6-7%• Crossover to PCI in medical therapy group: 6%Crossover to PCI in medical therapy group: 6%

At a mean f.u. time of 3 years…At a mean f.u. time of 3 years…

Medication at discharge

Published only on online supplement!!

The The SWSWiss iss IInterventional nterventional SStudy tudy on on SSilent ilent IIschemia Type II schemia Type II

To determine long-term outcome of asymptomatic To determine long-term outcome of asymptomatic subjects with silent ST-segment depression during subjects with silent ST-segment depression during exercise ECG exercise ECG andand silent myocardial ischemia silent myocardial ischemia documented by an imaging techniquedocumented by an imaging technique

To compare the effects of To compare the effects of PCI alonePCI alone with with anti-anti-ischemicischemic medical therapy on outcome, each medical therapy on outcome, each combined with secondary preventive advice, combined with secondary preventive advice, aspirin and statin therapyaspirin and statin therapy

Primary OutcomePrimary OutcomeCardiac death / Nonfatal MI / Cardiac death / Nonfatal MI /

symptom-driven PCI or CABGsymptom-driven PCI or CABG

• documented, first MI (STEMI or NSTEMI) within the documented, first MI (STEMI or NSTEMI) within the preceding 3 monthspreceding 3 months

• maximal symptom-limited exercise test without chest pain, maximal symptom-limited exercise test without chest pain, but with significant ST depressionbut with significant ST depression

• silent ischemia confirmed by stress imagingsilent ischemia confirmed by stress imaging• 1- to 2-vessel coronary artery disease (CAD) at coronary1- to 2-vessel coronary artery disease (CAD) at coronary

angiography (performed in angiography (performed in ALLALL patients) suitable for PCI patients) suitable for PCI

Inclusion CriteriaInclusion Criteria

Exclusion CriteriaExclusion Criteria• malignancymalignancy• symptomatic ischemiasymptomatic ischemia• 3V disease3V disease• no written informed consentno written informed consent

Enrolled to Screened

ratio~ 19%

May 1991 –February 1997

3 centers

PCI groupPCI group 27 (28%)27 (28%)

MED groupMED group 67 (64%)67 (64%)

Eve

nt-f

ree

surv

ival

Eve

nt-f

ree

surv

ival

Time from randomization (years)Time from randomization (years)

0.00

0.25

0.50

0.75

1.00

0 5 10 15

Log-rank: p < 0.001Log-rank: p < 0.001

Absolute event reduction: 6.3% per year (95% CI, 3.7%-8.9%; P < 0.001)Absolute event reduction: 6.3% per year (95% CI, 3.7%-8.9%; P < 0.001)Adjusted hazard ratio: 0.33 (95% CI, 0.20-0.55; P < 0.001)Adjusted hazard ratio: 0.33 (95% CI, 0.20-0.55; P < 0.001)

At a mean f.u. time of 10 years…At a mean f.u. time of 10 years…Primary composite end pointPrimary composite end point

1

10

16

7

37

23

0

10

20

30

40

50

60

Per

cen

tag

e

PCI group

MED group

Cardiacdeath

Non-fatal MI

PCICABG

At a mean f.u. time of 10 years…At a mean f.u. time of 10 years…Single end pointsSingle end points

Change in LVEF over time:PCI group: + 1.7%MED group: - 10.9%

SWISSI OAT COURAGEStudy population Silent ischemia

following first MI within 3 months

Total occlusion after MI within 1

month

Stable angina

Comment Patients highly selected for viable

myocardium

Most patients without viable myocardium

Enrolled to screened ratio

19% Not reported 6%

Exclusion criteria None based on EF EF >50% LVEF <30%

CAD 1- or 2-vessel (49%/51%)

82% 1-vessel 30% 3-vessel

Target of therapy Anti-ischemic Target-lesion PCIAggressive

medical therapy

Target-lesions PCI

Aggressive medical therapy

Mean f.u. length 10.2 years 3 years 4.6 years

Complete follow-up

96% 99% 91%

Cross-over treatments

16% in MED group received

PCI

6% in MED group received PCI

33% in MED group received

PCI

VIAMI study

VIability-guided Angioplasty afterAcute Myocardial Infarction

VIAMI

To demonstrate that, in MI patients after To demonstrate that, in MI patients after

thrombolysis or with late presentation, stenting of thrombolysis or with late presentation, stenting of

the infarct-related coronary artery will significantly the infarct-related coronary artery will significantly

reduce the risk of ischemia in patients with viability reduce the risk of ischemia in patients with viability

in the infarct-area (determined by dobutamine echo)in the infarct-area (determined by dobutamine echo)

To confirm that patients without viability haveTo confirm that patients without viability havea low risk of recurrent ischemic eventsa low risk of recurrent ischemic events

Primary OutcomePrimary OutcomeDeath / Recurrent MI / Death / Recurrent MI /

Unstable anginaUnstable angina

• Age 18 - 80 yrAge 18 - 80 yr• Acute MI treated with thrombolysisAcute MI treated with thrombolysis• (Sub) acute MI without reperfusion therapy(Sub) acute MI without reperfusion therapy• Uneventful before dobutamine echocardiography Uneventful before dobutamine echocardiography

Inclusion CriteriaInclusion Criteria

Exclusion CriteriaExclusion Criteria• Poor echo windowPoor echo window• Primary or rescue PCI for AMIPrimary or rescue PCI for AMI• Contraindications to coronary angiographyContraindications to coronary angiography

Acute myocardial infarction Acute myocardial infarction

(post-thromboysis or late presentation)(post-thromboysis or late presentation)

Low-dose dobutamine echo (48-72 h)Low-dose dobutamine echo (48-72 h)

viability no viabilityviability no viability

randomisation registryrandomisation registry

Infarct-related artery conservativeInfarct-related artery conservative stenting (+abciximab) ischemia-guidedstenting (+abciximab) ischemia-guided ((angio only inangio only in strategy strategy these patientsthese patients))

No angiographicNo angiographicexclusion criteriaexclusion criteria

Invasive Conservative Non-viableInvasive Conservative Non-viable (n=106) (n=110)(n=106) (n=110) (n=75) (n=75)

Age (y)Age (y) 60.8 60.8 59.7 59.7

63.763.7

Male (%)Male (%) 75 75 8080 66 66

Prior MI (%)Prior MI (%) 6 6 4 4 10 10

Anterior MI (%)Anterior MI (%) 31 31 3333 47 47

Thrombolysis (%)Thrombolysis (%) 53 53 4747 48 48

T. random – Angio (days) 2T. random – Angio (days) 2 - - - -

Protocol PCI (%)Protocol PCI (%) 73 73 - - - -

CABG (%)CABG (%) 1111 - - - -

No revascularisation (%)No revascularisation (%) 1616 - - - -

InvasiveInvasive ConservativeConservative (n=106)(n=106) (n=110)(n=110) p-valuep-value

Prim. Endpoint (%)Prim. Endpoint (%) 6.66.6 15.515.5 0.040.04 Death (%)Death (%) 1.91.9 0.90.9 nsns Recurrent MI (%)Recurrent MI (%) 1.91.9 2.72.7 nsns Unstable Angina (%)Unstable Angina (%) 2.82.8 11.811.8 0.0120.012

Elective revasc. (%)Elective revasc. (%) 00 17.317.3 < 0.01< 0.01All revascularisations (%)All revascularisations (%) 4.74.7 27.327.3 < 0.01< 0.01

At 6 months follow up…At 6 months follow up…

Non-Non- Viable-Viable-viableviable ConservativeConservative

(n=75)(n=75) (n=110)(n=110) Ischemic events (%)Ischemic events (%) 5.35.3 14.514.5 RR 65%RR 65%(UA or Recurrent MI)(UA or Recurrent MI) P < 0.05P < 0.05

• Patients with viability in the infarct-area significantly benefit Patients with viability in the infarct-area significantly benefit

from a strategy of early (in-hospital) stentingfrom a strategy of early (in-hospital) stenting

of the infarct-related coronary artery (+abciximab).of the infarct-related coronary artery (+abciximab).

This strategy results in a clear reduction of ischemic This strategy results in a clear reduction of ischemic

events and a long-term uneventful clinical courseevents and a long-term uneventful clinical course

• Patients without viability have a low incidence ofPatients without viability have a low incidence of

recurrent ischemic eventsrecurrent ischemic events

• Viability testing should become a standard toolViability testing should become a standard tool

in the clinical evaluation of patients in the earlyin the clinical evaluation of patients in the early

phase after thrombolysis and in STEMI-patients without phase after thrombolysis and in STEMI-patients without

reperfusion therapyreperfusion therapy

• In patients with viability revascularisation should be In patients with viability revascularisation should be

considered considered beforebefore hospital discharge hospital discharge

(Personal) Conclusions(Personal) Conclusions

• NEVERNEVER forget optimal medical therapy! forget optimal medical therapy!

• If the patient is (remains?) symptomatic… let’s treat!If the patient is (remains?) symptomatic… let’s treat!

• If the patient is asymptomatic… let’s search for If the patient is asymptomatic… let’s search for ischemia/viability… but only if high risk (example: post-MI… ischemia/viability… but only if high risk (example: post-MI… other subgroups: diabetics? post-CABG?)…other subgroups: diabetics? post-CABG?)…

• Avoid stress tests as “screening” in asymptomatic low-risk Avoid stress tests as “screening” in asymptomatic low-risk patients…patients…

• A lesion-based approach (“FFR” and “pullback FFR”), although A lesion-based approach (“FFR” and “pullback FFR”), although invasive, has the potential to be more accurate than a patient-invasive, has the potential to be more accurate than a patient-based approach (non-invasive stress tests)…based approach (non-invasive stress tests)…

For further slides on these topics For further slides on these topics please feel free to visit the please feel free to visit the

metcardio.org website:metcardio.org website:

http://www.http://www.metcardiometcardio..orgorg//slidesslides..htmlhtml