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Management of Stable Angina in Multivessel Disease: Reconciling the Results of the Randomized Trials Eric A. Cohen MD, FRCPC Schulich Heart Centre Sunnybrook Health Sciences Centre Toronto ON ACC Rockies March 11, 2014 Mgmt of Multivessel

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Management of Stable Angina in Multivessel Disease:

Reconciling the Results of the Randomized Trials

Eric A. Cohen MD, FRCPC

Schulich Heart Centre Sunnybrook Health Sciences Centre Toronto ON

ACC Rockies March 11, 2014

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Disclosure – Eric Cohen

Relevant to this presentation:

  • Consulting / Advisory Board - Medtronic Vascular

Mgmt of Multivessel Disease

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Disclosure – Eric Cohen

Relevant to this presentation:

  • Consulting / Advisory Board - Medtronic Vascular
  • Volume dependent (i.e. mostly fee for service) interventional

cardiologist

Mgmt of Multivessel Disease

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Management of Stable Angina in Multivessel Disease:

Reconciling the Results of the Randomized Trials

  • Management, not revascularization . . .
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Management of Stable Angina in Multivessel Disease:

Reconciling the Results of the Randomized Trials

  • How relevant is it to distinguish the acuity of

the presentation?

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Management of Stable Angina in Multivessel Disease:

Reconciling the Results of the Randomized Trials

  • Is it angina that matters or is it ischemia?
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rec·on·cile (verb)

  • to find a way of making (two different ideas, facts, etc.) exist or be true at

the same time

  • to cause people or groups to become friendly again after an argument or

disagreement

Mgmt of Multivessel Disease

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Management of Stable Angina in Multivessel Disease:

Reconciling the Results of the Randomized Trials

Reconcile because . . .

  • various trials yield discordant results?
  • the trial results don’t match our pre-conceived notions?
  • the patients in the trials don’t look like those in our day to day

practice?

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Management of Stable Angina in Multivessel Disease:

Reconciling the Results of the Randomized Trials

And in the end . . . I promise to tell you whether surgery is truly better than PCI

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  • 1. Does revascularization matter?

Mgmt of Multivessel Disease

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Meta-Analysis of CABG vs. Medical Therapy: 7 Randomized Trials

Yusuf S et al, Lancet 1994

Mortality

Mgmt of Multivessel Disease

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Extension of Survival (in months) at 10 Years After CABG in Various Subgroups

Relevance today is unclear. There was minimal or no use of effective medical therapy (ASA, statins, beta-blockers, ACE inhibitors).

N=150 N=1300 N=550

Yusuf et al. Lancet. 1994;344:563-570.

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STITCH: CABG + OMT vs. OMT in CAD/CHF Primary Endpoint: All-Cause Mortality (ITT)

HR 0.86 (0.72, 1.04) P = 0.123 Adjusted HR 0.82 (0.68, 0.99) Adjusted P = 0.039

0.46 (218/610) 0.41 (244/602)

Velazquez E et al., NEJM 2011;364:1607-16

As treated

HR 0.70 (0.58, 0.84) P <0.001

Per protocol

HR 0.76 (0.62, 0.92) P = 0.005

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PCI Did Not Reduce Death or MI

Number at Risk

Medical Therapy 1138 1017 959 834 638 408 192 30 PCI 1149 1013 952 833 637 417 200 35 Years 1 2 3 4 5 6 0.0 0.5 0.6 0.7 0.8 0.9 1.0

PCI + OMT Optimal Medical Therapy (OMT)

Hazard ratio: 1.05 95% CI (0.87-1.27) P = 0.62

7

Boden et al NEJM 2007

18.5% 19.0%

2,287 SIHD patients randomized to PCI+OMT vs. OMT

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BARI 2D Study Group. N Engl J Med 2009;360:2503-2512.

BARI 2D

  • 2,368 SIHD patients with diabetes

randomized to revascularization + OMT or OMT alone

  • Primary endpoint: all-cause death
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  • 1. Does revascularization matter?
  • What prevents mortality from stable CAD?
  • PCI vs CABG
  • Large group of pts for which the mode of revascularization does

not seem to matter

  • What prevents mortality from the common cold?
  • decongestant vs cough suppressant

Mgmt of Multivessel Disease

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  • 2. Does the acuity of presentation matter?
  • Data on revascularization vs med Rx more compelling in ACS
  • Very little comparative data on PCI vs CABG in unstable disease
  • More pts are identified and treated in the acute phase, thus

fewer who present in a chronic phase

  • More challenging to do trials involving management of stable

CAD

Mgmt of Multivessel Disease

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  • 3. Are the trial results fundamentally different?

Mgmt of Multivessel Disease

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Hlatky et al, The Lancet 2009;373:1190-1197

10 RCTs 7812 Pts: CABG vs. PCI: No Difference in Death and MI

CABG 3889 3767 3675 3415 3180 2693 1853 1609 1477 PCI 3923 3798 3709 3431 3205 2658 1828 1576 1452

Years of follow-up Mortality (%) CABG PCI

35 30 25 20 15 10 5 1 2 3 4 5 6 7 8

  • No. of patients*

Death or myocardial infarction (%)

CABG 3695 3369 3269 3001 2763 2294 1501 1269 1161 PCI 3725 3419 3310 3023 2797 2267 1491 1253 1150

Years of follow-up

35 30 25 20 15 10 5 1 2 3 4 5 6 7 8

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Revascularization in Diabetic Patients:

Randomized Trials - Diabetic Subgroup

Diabetic - CABG Diabetic - PTCA Non-Diabetic - CABG Non-Diabetic - PTCA

BARI Trial - Main Results

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Revascularization in Diabetic Patients:

Registry Data - Diabetic Subgroup

BARI Trial - Registry vs Randomized; Insulin vs Oral

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CABG vs PCI :Death and Diabetic Status

Number of patients* CABG no diabetes 3263 3169 3089 2877 2677 2267 1592 1380 1274 CABG diabetes 615 587 575 532 498 421 257 225 200 PCI no diabetes 3298 3217 3148 2918 2725 2281 1608 1393 1288 618 574 555 508 475 373 218 179 160

Years of follow-up Mortality (%)

CABG no diabetes CABG diabetes PCI no diabetes PCI diabetes

35 30 25 20 15 10 5 1 2 3 4 5 6 7 8

PCI diabetes

Hlatky et al, The Lancet 2009;373:1190-1197

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Mgmt of Multivessel Disease

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Mgmt of Multivessel Disease

  • In the modern era of stenting and optimum medical therapy,

revascularisation of patients with diabetes and multivessel disease by CABG decreases long-term mortality by about a third compared with PCI using either BMS or DES. CABG should be strongly considered for these patients.

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Fastest growing industries - 2013

Mgmt of Multivessel Disease

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The single fastest growing industry . . .

Decade

PubMed listings 1960’s 1970’s 2 1980’s 254 1990’s 2455 2000’s 9912 2010 - 2014 18635

Mgmt of Multivessel Disease

With “meta-analysis” in the title

In the same time period there were 6565 entries with “clinical trial” in the title

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  • 4. Are my patients similar to the patients in these

trials?

Mgmt of Multivessel Disease

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Indications for CABG vs PCI in stable patients with lesions suitable for both procedures and low predicted surgical mortality

Subset of CAD by anatomy Favours CABG Favours PCI 1VD or 2VD – non proximal LAD IIb C I C 1VD or 2VD – proximal LAD I A IIa B 3VD simple lesions, full functional revascularization achievable with PCI, SYNTAX score ≤ 22 I A IIa B 3VD complex lesions, incomplete revascularizarion achievable with PCI, SYNTAX score > 22 I A III A Left main (isolated or 1VD, ostium/shaft) I A IIa B Left main (isolated or 1VD, bifurcation) I A IIb B Left main + 2VD or 3VD, SYNTAX score ≤ 32 I A IIb B Left main + 2VD or 3VD, SYNTAX score ≥ 33 I A III B ESC guidelines 2010

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  • 4. Are my patients similar to the patients in these

trials?

Mgmt of Multivessel Disease

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“In theory, theory and practice are the same. In practice, they are not.”

Albert Einstein

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Mainly 1 or 2 vessel disease With preserved LVEF Few diabetic patients Highly selected population

Trials of PCI vs CABG: generalizability

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SYNTAX score – randomized vs registry

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Cardiac Cath, PCI and CABG in Ontario Trends in Volumes (FY 1999-2010)

10000 20000 30000 40000 50000 60000 70000 Case Volume Cath PCI CABG

Mgmt of Multivessel Disease

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PCI:CABG Ratio 2000/01 -2010/11

0.5 1 1.5 2 2.5 3 3.5 PCI:CABG

Mgmt of Multivessel Disease

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Overall Ratio = 2.7

0.00 1.00 2.00 3.00 4.00 5.00 6.00 7.00

Hotel

  • Dieu

London Thunder Bay

  • St. Mary's

Peterborough Rouge Valley Trillium Hamilton Southlake Toronto East UHN Kingston Sunnybrook

  • St. Michael's

Ottawa Sudbury Sault Ste Marie

Hospital Overall PCI / CABG Ratio

1.33 1.40 1.79 1.92 2.24 2.14 2.14 2.39 2.79 2.91 3.01 3.24 3.24 3.91 4.75 4.90 6.15

Low Ratio Low

  • Medium Ratio

Medium

  • High Ratio

High Ratio

Groupings of Hospitals by PCI:CABG ratio for VRPO cohort (N=8,972)

Mgmt of Multivessel Disease

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Multivariate Logistic Regression Model for Predicted Probability of Being Treated with PCI Rather than CABG (N=4,285)

Variable Odds Ratio Est Lower 95% CL Upper 95% CL p-value Anatomy (vs 3 vessel) 1 vessel 37.6 28.1 50.2 <.001 2 vessel 5.6 4.5 7.0 <.001 Left main 0.3 0.2 0.4 <.001 Prior CABG 28.7 17.9 45.9 <.001 Indication (vs Elective stable CAD) Unstable angina 0.9 0.7 1.1 0.3 NSTEMI 1.3 1.1 1.7 0.02 Non-emergent STEMI 1.6 1.0 2.4 0.03 Emergent STEMI 7.6 5.1 11.3 <.001 Physician factors (vs. Non-interventionalist) Interventionalist 1.4 1.2 1.7 <.001 Hospital factors (vs Low Ratio Hospitals) Low-Medium ratio hospitals 1.3 1.0 1.7 0.02 Medium-High ratio hospitals 2.0 1.5 2.6 <.001 High Ratio Hospitals 3.7 2.7 4.9 <.001 C-statistic=0.89.*Also adjusted for age/gender, diabetes and previous PCI CL = Confidence limit Mgmt of Multivessel Disease

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Percentage of Revascularized Patients who Received PCI by Hospital PCI:CABG Ratio Category

10 20 30 40 50 60 70 80 90 100

1 vessel 2 or 3 vessel Left main Prior CABG

Percent (%)

Low Low-Medium Medium-High High

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5 Factors Contribute to PCI vs. CABG Decision Making

1. Patient factors 2. Clinical evidence 3. Physician/practice preferences 4. Relationships amongst providers 5. Institutional factors (physical and “cultural”)

Mgmt of Multivessel Disease

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ESC Revascularization Guidelines 2010

Mgmt of Multivessel Disease

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AHA Guidelines Nov 2011

Mgmt of Multivessel Disease

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Class I Recommendation

“Heart Team Approach to Revascularization Decisions”

  • Interventional cardiologist, cardiac surgeon and cardiologist
  • Reviews medical condition & coronary anatomy
  • Determines that PCI and/or CABG are reasonable and feasible.
  • Discusses options with patient before a treatment strategy is

selected

Mgmt of Multivessel Disease

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Sobering?

  • That we can start and end our careers still trying to answer the

same question

Mgmt of Multivessel Disease

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Interactions...

Syntax score AGE Cr Cl EF 3VD LMS F M COPD PVD

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Interactions...

Syntax score AGE Cr Cl EF 3VD LMS F M COPD Diabetes

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FFR-guided SYNTAX Score (FSS) versus Conventional SYNTAX Score (SS) and Clinical Outcome LOW risk 33% MEDIUM risk 33% HIGH risk 33% LOW risk 59 % MEDIUM risk 21% HIGH risk 21% FSS SS

32% of patients moved to a lower-risk group

  • 497 patients of the FFR-arm of FAME I
  • Syntax scored re-calculated by 3 incdependant reviewers
  • 3 tertiles based on SS

www.cardio-aalst.be

FAME, SYNTAX, COURAGE, ... Nam, C.W. et al. JACC 2011

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SYNTAX II

  • 3-vessel-disease, all comers, any SYNTAX score
  • contemporary PCI practice
  • contemporary stent with thinner struts, biodegradable polymer, limus-

based drug

  • use of pressure wire assessment (FFR and iFR) to allow for ischemia-

driven revascularisation

  • intravascular ultrasound (IVUS) guidance to optimise stent deployment
  • treatment of CTO lesions with contemporary techniques
  • all of these differ from PCI practice in the original SYNTAX trial

clinicaltrials.gov (accessed March 9, 2014)

A Trial to Evaluate a New Strategy in the Functional Assessment of 3-vessel Disease Using the SYNTAX II Score in Patients Treated With PCI

Mgmt of Multivessel Disease

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Patient with stable CAD

Forces in play

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Forces in play

Mgmt of Multivessel Disease

Patient with stable CAD

Medical Rx Revascularization

COURAGE BARI-2D STICH CASS, VA COURAGE Nuclear Old silent ischemia studies (ACIP, SWISS) Appropriate Use Criteria Bad press, overutilization Importance of ischemia, viability, complete revasc, CTO’s

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Mgmt of Multivessel Disease

Patient with stable CAD

Medical Rx Revascularization PCI CABG

COURAGE BARI-2D STICH CASS, VA COURAGE Nuclear Old silent ischemia studies (ACIP, SWISS) Appropriate Use Criteria Bad press, overutilization Importance of ischemia, viability, complete revasc, CTO’s

  • Anatomic complexity

and diabetes

  • Completeness of

revascularization

  • LV dysfunction

FAME II BARI (diabetes) FREEDOM SYNTAX

  • Comorbidity, renal disease
  • Combined functional &

anatomic assessment

  • Better stents
  • CTO technology

Hybrid procedures

Forces in play

BARI (no diabetes)

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Mgmt of Multivessel Disease

Patient with stable CAD

Medical Rx Revascularization PCI CABG

COURAGE BARI-2D STICH CASS, VA COURAGE Nuclear Old silent ischemia studies (ACIP, SWISS) Appropriate Use Criteria Bad press, overutilization Importance of ischemia, viability, complete revasc, CTO’s

  • Anatomic complexity

and diabetes

  • Completeness of

revascularization

  • LV dysfunction

FAME II BARI (diabetes) FREEDOM SYNTAX

  • Comorbidity, renal disease
  • Combined functional &

anatomic assessment

  • Better stents
  • CTO technology

Hybrid procedures

Forces in play

BARI (no diabetes)