Treatment strategies for “stable” CAD patients: COURAGE, OAT, SWISSI II, VIAMI in perspective Pierfrancesco Agostoni, MD Antwerp Cardiovascular Institute Middelheim Department of Interventional Cardiology

Clinical Outcomes Utilizing Revascularization And Aggressive DruG Evaluation

To determine whether PCI plus optimal medical therapy (OMT) reduces the risk of death or nonfatal MI in symptomatic patients with stable CAD, as compared with OMT alone. Patients with stable angina (CCS I-III or initial CCS IV medically stabilized) ALL underwent coronary angiography and where then randomized to PCI + OMT vs. OMT alone Primary Outcome Death or Nonfatal MI

1, 2, or 3 vessel disease (> 80% visual stenosis of proximal coronary segment)1, 2, or 3 vessel disease (> 80% visual stenosis of 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 therapy Complicated post-MI course Complicated post-MI course Revascularization within 6 months Revascularization within 6 months Ejection fraction <30% Ejection fraction <30% Cardiogenic shock/severe heart failure Cardiogenic 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 Criteria Exclusion 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…

But… if we look at quality of life…

Is this a “transient” reduction??

and effectively performed

Occluded Artery Trial

To evaluate outcomes of percutaneous coronary intervention (PCI) versus medical therapy among stable, high-risk, asymptomatic patients with persistent total occlusion of the infarct-related artery post-myocardial infarction (MI). Patients presenting late post-MI ALL underwent angiography from >24 hours to 28 days post-MI and were randomized to PCI of the IRA + optimal medical therapy or conservative medical therapy Primary Outcome Death / Nonfatal MI / NYHA IV HF

Inclusion Criteria Exclusion Criteria total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow 0 or 1)total occlusion of the infarct-related artery with poor or absent antegrade flow (TIMI flow 0 or 1) increased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with a large risk region, or bothincreased risk, defined as ejection fraction <50%, proximal occlusion of a major epicardial vessel with a large risk region, or both NYHA class III-IV heart failure or caridogenic shock NYHA class III-IV heart failure or caridogenic shock serum creatinine concentration >2.5 mg/dl serum creatinine concentration >2.5 mg/dl significant LM or 3-V coronary artery disease significant LM or 3-V coronary artery disease angina at rest angina at rest severe ischemia on stress testing severe ischemia on stress testing

ST depression >2 mm No completion of stage 1 Reversible perfusion defects in 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…

Medication at discharge Published only on online supplement!!

The SWiss Interventional Study on Silent Ischemia Type II

To determine long-term outcome of asymptomatic subjects with silent ST-segment depression during exercise ECG and silent myocardial ischemia documented by an imaging technique To compare the effects of PCI alone with anti- ischemic medical therapy on outcome, each combined with secondary preventive advice, aspirin and statin therapy Primary Outcome Cardiac death / Nonfatal MI / symptom-driven PCI or CABG

documented, first MI (STEMI or NSTEMI) within the preceding 3 monthsdocumented, first MI (STEMI or NSTEMI) within the preceding 3 months maximal symptom-limited exercise test without chest pain, but with significant ST depressionmaximal symptom-limited exercise test without chest pain, but with significant ST depression silent ischemia confirmed by stress imagingsilent ischemia confirmed by stress imaging 1- to 2-vessel coronary artery disease (CAD) at coronary angiography (performed in ALL patients) suitable for PCI1- to 2-vessel coronary artery disease (CAD) at coronary angiography (performed in ALL patients) suitable for PCI Inclusion Criteria Exclusion Criteria malignancy malignancy symptomatic ischemia symptomatic ischemia 3V disease 3V disease no written informed consent no written informed consent

Enrolled to Screened ratio ~ 19% May 1991 – February centers

PCI group27 (28%) MED group67 (64%) Event-free survival Time from randomization (years) Log-rank: p < Absolute event reduction: 6.3% per year (95% CI, 3.7%-8.9%; P < 0.001) Adjusted hazard ratio: 0.33 (95% CI, ; P < 0.001) At a mean f.u. time of 10 years… Primary composite end point

PCI group MED group Cardiac death Non- fatal MI PCI CABG At a mean f.u. time of 10 years… Single end points

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

SWISSIOATCOURAGE Study populationSilent ischemia following first MI within 3 months Total occlusion after MI within 1 month Stable angina CommentPatients highly selected for viable myocardium Most patients without viable myocardium Enrolled to screened ratio 19%Not reported6% Exclusion criteriaNone based on EFEF >50%LVEF <30% CAD1- or 2-vessel (49%/51%) 82% 1-vessel30% 3-vessel Target of therapyAnti-ischemicTarget-lesion PCI Aggressive medical therapy Target-lesions PCI Aggressive medical therapy Mean f.u. length10.2 years3 years4.6 years Complete follow-up96%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 after Acute Myocardial Infarction VIAMI

To demonstrate that, in MI patients after thrombolysis or with late presentation, stenting of the infarct-related coronary artery will significantly reduce the risk of ischemia in patients with viability in the infarct-area (determined by dobutamine echo) To confirm that patients without viability have a low risk of recurrent ischemic events Primary Outcome Death / Recurrent MI / Unstable angina

Age yrAge 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 echocardiographyUneventful before dobutamine echocardiography Inclusion Criteria Exclusion 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) Low-dose dobutamine echo (48-72 h) Low-dose dobutamine echo (48-72 h) viability no viability viability no viability randomisation registry randomisation registry Infarct-related artery conservative Infarct-related artery conservative stenting (+abciximab) ischemia-guided stenting (+abciximab) ischemia-guided (angio only in strategy (angio only in strategy these patients) these patients) No angiographic exclusion criteria

Invasive Conservative Non-viable Invasive Conservative Non-viable (n=106) (n=110) (n=75) (n=106) (n=110) (n=75) Age (y) Male (%) Prior MI (%) Anterior MI (%) Thrombolysis (%) T. random – Angio (days) Protocol PCI (%) CABG (%) No revascularisation (%)

InvasiveConservative InvasiveConservative (n=106)(n=110) p-value (n=106)(n=110) p-value Prim. Endpoint (%) Death (%)1.90.9ns Death (%)1.90.9ns Recurrent MI (%)1.92.7ns Recurrent MI (%)1.92.7ns Unstable Angina (%) Unstable Angina (%) Elective revasc. (%)017.3< 0.01 All revascularisations (%) < 0.01 At 6 months follow up… Non-Viable- Non-Viable- viableConservative (n=75)(n=110) (n=75)(n=110) Ischemic events (%) RR 65% (UA or Recurrent MI)P < 0.05

Patients with viability in the infarct-area significantly benefit from a strategy of early (in-hospital) stentingPatients with viability in the infarct-area significantly benefit from a strategy of early (in-hospital) stenting of the infarct-related coronary artery (+abciximab). This strategy results in a clear reduction of ischemic events and a long-term uneventful clinical course Patients without viability have a low incidence ofPatients without viability have a low incidence of recurrent ischemic events Viability testing should become a standard toolViability testing should become a standard tool in the clinical evaluation of patients in the early phase after thrombolysis and in STEMI-patients without reperfusion therapy In patients with viability revascularisation should be considered before hospital dischargeIn patients with viability revascularisation should be considered before hospital discharge

(Personal) Conclusions NEVER forget optimal medical therapy!NEVER 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 ischemia/viability… but only if high risk (example: post-MI… other subgroups: diabetics? post-CABG?)…If the patient is asymptomatic… let’s search for ischemia/viability… but only if high risk (example: post-MI… other subgroups: diabetics? post-CABG?)… Avoid stress tests as “screening” in asymptomatic low-risk patients…Avoid stress tests as “screening” in asymptomatic low-risk patients… A lesion-based approach (“FFR” and “pullback FFR”), although invasive, has the potential to be more accurate than a patient- based approach (non-invasive stress tests)…A lesion-based approach (“FFR” and “pullback FFR”), although invasive, has the potential to be more accurate than a patient- based approach (non-invasive stress tests)…

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