Controversies in Cardiology: Stable CAD

1
Controversies in CardiologyStable CAD
COURAGE Pro Optimal Medical Therapy vs. PCI

• William E. Boden, MD, FACC, FAHA
• Professor of Medicine Preventive Medicine
• University at Buffalo Schools of Medicine and
  Public Health
• Chief of Cardiology, Buffalo General/Millard
  Fillmore Hospitals, Buffalo, NY
• 23rd Annual ACC Florida Chapter Meeting
  Scientific Session
• Orlando, FL
• August 21, 2009

Disclosure Dr. Boden receives research grants,
speakers bureau honoraria, or is a consultant to
the following companies Abbott,
Glaxo-Smith-Kline, Gilead Scientific, Merck,
Pfizer, Sanofi-Aventis
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Stable Angina
3
Increased Mortality with Medical Management for
UA/NSTEMI PatientsPatients with Significant CAD
on Cath in the SYNERGY Trial
Med Management (MM), Percutaneous Coronary
Intervention (PCI), Coronary Artery Bypass
Grafting (CABG)
Chan M, JACC Cardiovasc Int 2008
4
A Different Story in Stable CADContrasting 1
Year Death/MI Rates ACS, Stable Angina,
Primary Prevention
Death/ MI ()
Unstable angina/non Q wave MI (FRISC II)
Stable angina (SAPAT)
Primary Prevention (WOSCOPS)
ACTION trial (stable CAD)
0
2
4
6
8
10
12
Months of follow up
Wallentin L et al. Lancet 2000356916 Juul-Molle
r S et al. Lancet 199234014211425 Shepherd J
et al. N Engl J Med 199533313011307 Poole-Wilso
n et al ACTION Lancet 2004364849-57.
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What Is The Concern Of Leaving Coronary Stenoses
Alone?

• In Patients with Chronic Angina and Stable CAD
• We know that PCI improves angina and short-term
  exercise capacity, so if we dont fix what we
  see
• Will we expose patients to increased risk of
  death/MI?
• Will angina and quality of life be worse?
• Will residual ischemia be less well treated?
• Will patients feel they did not receive best
  care?
• What about high-risk patients3V CAD ? EF?

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Evidence Prior to COURAGE of Leaving Coronary
Stenoses Alone
RITA-2, 1018 patients (504 PTCA, 514 medical
management)
Death or MI
Death
PNS
PNS
No difference in outcome over median of 7 years
(Henderson, et al. JACC 2003421161)
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Stable CAD PCI vs. Medical Management Pre-COURAGE
Meta-analysis of 11 randomized trials N 2950
Favors PCI
Favors Medical Management
0
1
2
Risk ratio (95 Cl)
Katritsis DG et al. Circulation. 20051112906-12.
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COURAGE Primary EPSurvival Free of Death or MI

• 2,287 Pts. Randomized to PCI OMT vs. OMT
• Intensive, Guideline-Driven Medical Therapy
  Lifestyle Intervention In Both Groups

Optimal Medical Therapy (OMT)
1.0
0.9
0.8
PCI OMT
0.7
Hazard ratio 1.05 95 CI (0.87-1.27) P 0.62
0.6
0.5
0.0
0
1
2
3
4
5
6
7
Years
Source Boden et al. N Engl J Med. 2007
3561503-16.
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Optimal Medical Therapy

• Pharmacologic
• Anti-platelet aspirin clopidogrel (c/w with
  established practice standards)
• Statin simvastatin ezetimibe or
  extended-release niacin
• ACE Inhibitor or ARB lisinopril or losartan
• Beta-blocker long-acting metoprolol (Toprol XL)
• Calcium channel blocker amlodipine
• Nitrate isosorbide 5-mononitrate
• Lifestyle
• Smoking cessation
• Exercise program
• Nutrition counseling
• Weight control

Applied to Both Arms by Protocol and Case-Managed
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Long-Term Improvement in Treatment Targets (Group
Median SE Data)
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Value of Optimal Medical TherapyThe COURAGE
Trial
Compared with Optimal Medical Therapy Alone, PCI
provided no incremental benefit on Death, MI, New
ACS
Death/MI
Death
New ACS
New MI
(Boden, et al. NEJM 20073561503)
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Tertiary Outcomes Cardiac Death/MI/ACS
30
23.5
PCI OMT
Hazard ratio 1.07 CI 95 (0.91, 1.27) P 0.60
22.6
20
OMT
10
0
1
2
3
4
5
6
Years
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COURAGE Enrolled Low-Risk Patients Huh???

• Angina at BL 88
• Angina Duration 26 mo
• Angina Freq. 6 episodes/wk
• Multivessel CAD 70
• LAD disease 68
• Inducible Ischemia 85
• Stress MPI Multiple defects 67
• Death/MI Event Rate 4.3/year

• Diabetes 34
• Dyslipidemia 71
• HTN 67
• Smokers 29
• Prior MI 39
• Prior Revasc 26

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COURAGE Patient Randomized to OMT Alone
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COURAGE Patient Randomized to OMT Alone
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Need for Subsequent Revascularization 7 Years of
F/U
Median 4.6 years of follow-up Median time to
Repeat or 1st Revascularization After 11 mo,
the avg. X-over from OMT to PCI was 2.8/year
over years 1-7
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Freedom from CCS Angina During Follow-up NNT to
Improve Sx
The comparison between the PCI group and the
medical-therapy group was significant at 1 year (
Plt0.001) and 3 years (P0.02) but not at baseline
or 5 years.
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SAQ Mean QOL Scores During Follow-up NNT to
Improve Sx
P lt 0.001 between groups
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COURAGE QOL Editorial Commentary
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Nuclear Substudy (n314)
Hypothesis Reduction in Ischemia will be greater
for Pts. Randomized to PCIOMT than for those
Randomized to OMT as Measured By Changes in
Ischemic Burden by MPS at Baseline 6-18m after
Randomization

• Rest/Stress Myocardial Perfusion SPECT (MPS)
• Pre-Rx
• Following 6-18m Randomized Rx (mean 374 50
  days)

Source Shaw et al. J Nucl Cardiol 2006
Sep13(5)685-98.
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Quantitative Ischemic Myocardium in COURAGE
Nuclear Substudy

• N 314 Patients (PCI OMT 159 OMT Alone 155)
• Ischemic Myocardium Stress TPD-Rest TPD
• lt 5 Minimal (No Ischemia) 51
• 5.0-9.9 Mild 29
• ?10 Moderate-to-Severe 20
• ?5 Change in Ischemic Myocardium Significant

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MPS Ischemia Pre-Rx 6-18 Mos. Following PCI
OMT vs. OMT
OMT (n155)
PCI OMT (n159)
8.1 (6.9-9.4)
8.6
8.2
5.5 (4.7-6.3)
plt0.0001
Mean-0.5 (95 CI-1.6 to 0.6)
Mean-2.7 (95 CI-1.7 to -3.8)
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Unadjusted and Risk-Adjusted Outcomes for
Reduction in Ischemic Myocardium
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Patient Expectations AboutElective PCI for
Stable CAD

• 52 consecutive patients scheduled for first
  elective PCI completed semi-structured
  questionnaire prospectively

Holmboe et al. J Gen Intern Med 200015632.
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Recent Mid-America Heart Institute Patient PCI
Survey

• One million PCI procedures per year
• Majority elective
• Prospective survey of 350 elective PCI patients
  with stable CAD _at_ MAHI between 1/06-10/07
• Focus are pt. perspectives of PCI benefit
  aligned with current evidence?
• John H. Lee, MD et al 2008 AHA Scientific
  Sessions, November 12, 2008

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Patient Perceived Benefitsof Elective PCI
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Alternate Therapies Offered
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Stenosis Severity prior to AMI What Drives Late
Events is CAD Progression in Non-Flow- Limiting
Lesions ? New Plaque Rupture
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PARADIGM Chronic CAD is a Systemic Disease with
Focal Exacerbations and Manifestations
Revascularization Anti-Anginal Rx
Pharmacologic Stabilization ? Vascular Disease
Modification
(Stone, 2007)
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PARADOX Major Cardiac Events Occur in
Non-Target Areas Following Successful PCI
5 year Followup of 1228 Patients Treated with
Bare Metal Stents

• Non-target Lesion
• Event Rates
• 12.4 Year 1
• 37.4 Year 1-5

18.3
12.4
Hazard Rate ()
6.7
7.0
5.6
5.7
2.3
1.5
1.4
1.3
(Cutlip, et al. Circulation 20041101226)
Substantial number of cardiac events could be
prevented if we knew how to identify them
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Schomig Meta-Analysis of Stable CAD (includes 5
AMI/post-MI RCTs) J Am Coll Cardiol
200852894
P lt 0.001 between groups
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Jeremias Meta-Analysis of Revascularization
for Stable CAD on Mortality (includes 8 CABG
and 5 AMI/post-MI RCTs) Am J Med
2009 122, 152-161
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Recent Corrected Meta-Analysis of PCI vs. OMT
on Mortality
Wijeysundera and Ko Circulation CQO 2009 2
123-126
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Why The Evidence Supports OMT as
the Initial Approach to
Stable CAD Management

• For Patients Undergoing Elective Coronary
  Angiography for Chronic Angina
• 13 RCTs in 7,605 patients (including BARI-2D)
  show no difference in death, MI, stroke or other
  hard endpoints between PCI and OMT
• An initial course of OMT preserves the option for
  PCI if medical therapy fails (only 16.5 of
  COURAGE OMT patients crossed over to PCI within
  1 year)
• Over a full 7-year follow-up period, 2/3 of all
  OMT patients never required even a 1st PCI
  procedure

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Where Does COURAGE Give Us Clarity of Management?

• In Patients with Chronic Angina and Stable CAD
• There is better angina relief with PCI over 1-3
  years
• There is better QOL with PCI over 1-2 years
• The subsequent need for revascularization in the
  1st year is lower in PCI than OMT patients
• OMT is a safe viable option for most patients,
  and for those who may not be good candidates for
  PCI (frailty CKD multiple co-morbidities
  treacherous anatomy, etc.)
• OMT as an initial approach preserves PCI as a
  subsequent option for symptom/QOL relief, if
  needed

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Where Do the Results of COURAGE Still Leave
Uncertainty?

• In Patients with Chronic Angina and Stable CAD
• Is OMT as good as PCI OMT in patients with
  impaired LV systolic function (EF lt 40)?
• Do patients with high-grade 3-vessel CAD fare as
  well with OMT vs. PCI OMT, esp. with EF lt 40?
• Does stenosis severity ( 90 vs. 70-80) alter
  PCI vs. OMT outcomes, and does defining coronary
  anatomy in all patients aid clinical
  decision-making?
• Is it important to delineate the presence or
  absence of high-risk inducible ischemia in all
  patients?

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COURAGE Post-Hoc QCA Analysis of CAD EF
G.B.John Mancini, MD University of British
Columbia (AHA 2007)
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Proposed New NHLBI Trial

• ISCHEMIA Trial International Study of
  Comparative Health Effectiveness using Medical
  and Interventional Approaches
• Steering Committee Judy Hochman (PI) David
  Maron, Bill Boden, Gregg Stone, David Williams,
  Bob Harrington

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Stable CAD 10 Ischemia by MPI or similarly
High-Risk Ischemia by Echo
Provisional Consent, phone in patient all will
be registered
Screening log with dynamic sampling for
potentially eligible patients not consented
Arm selection according to site MD
Pre-Cath randomization arm
Post-Cath randomization arm
Alternate pathway
Cath done, site recognizes possible eligibility
Blinded CCTA for high risk stress or MD preference
Cath
Exclude and register LM , normals,
non-revascularizable disease
Exclude LM and normals
Provisional Consent, phone in, register
Require stress test, pt enrolled if ischemia
criteria met
Randomization
Randomization, stratified by intent PCI or CABG
Cath Revasc OMT
OMT
Revasc OMT
OMT
Overall Composite Primary End Point Total
Mortality, Nonfatal MI Composite Secondary End
Point for Each Arm D/MI/Class III-IV HF/ACS Hosp
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The Case for Medical Therapy as the Initial
Choice in Chronic Stable Angina

• Aggressive medical therapy lifestyle
  intervention without initial PCI can be
  implemented safely in the majority of patients
  with stable CAD1/3 of whom may require a
  symptom-driven procedure over 7 years of F/U, but
  2/3 of whom may not require even a first
  revascularization. This approach incurs no
  disadvantage with respect to death, MI, ACS, or
  need for CABG.
• 2. Although routine PCI OMT provides some
  advantages in angina/physical limitation/QOL,
  these differences are numerically small, not
  durable, and achieved only at an unattractive
  cost for chronic disease management.

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A Final Vote of Support for Optimal Medical
Therapy