Post on 19-Jan-2016
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