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Update in Coronary Artery Disease

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					        Update in CAD:
“To Stent or not to Stent: is that
      the real question?”
     Gustavo R. Heudebert, MD
     Division of General Internal
              Medicine
               Road Map
Background Information
Medical therapy or revascularization?
Which stent is better/safer?
Matching stents to patients
Long term management of DES
                Case#1
A 55 year old male non diabetic with stable
angina has noticed chest pain with less
exercise but not at rest. No other symptoms.
BP 138/62. BMI of 29. Rest of PE unchanged.
EKG without any new changes.
LDL is 94 mg/dl. No tobacco use. Sedentary.
Would you refer for LHC and possible PCI?
                 Case #2
A 62 year old female with known CAD comes
for a routine follow-up visit. She has T2DM,
HTN, and is a former smoker. She had a PCI
to the LCx (DES) 12 months ago and is doing
well. Her medications include metformin, a
beta blocker, ASA, clopidogrel, and an ACE-I.
What further recommendations do you have
regarding her anti-platelet therapy?
                 Background
Most common cause of death in the US
   Most costly diagnosis
One in five Americans have CAD by age 70
Lifetime risk (at age 40)
   Males: 49%
   Females: 32%
Mortality is falling
                 Background
Clinical presentation
   Acute Coronary Syndrome
   Chronic Stable Angina
   Silent Ischemia
Management
   Medical Management
     Medications, lifestyle modifications
   Revascularization
     PCI and CABG
        Terminology of Angina
Stable angina
   Angina that occurs predictably and reproducibly
   at the same level with exercise and is relieved
   with rest or nitroglycerin.
Unstable angina
   A variety of clinical conditions including the new
   onset of chest pain, rest angina, an accelerating
   pattern of previously stable angina, post-
   myocardial infarction (MI) angina, and angina
   after a revascularization procedure
             Angioplasty Story
First deployed in 1977
   Very high risk of re-stenosis
   Improved with use of aspirin
Stents
   Bare metal: approved by FDA in 1994
      Less re-stenosis
      Further improved by thienopyridines
   Drug Eluting: introduced in 2003
                   DES Story
Polymer coated stent with anti-proliferative
 agents (sirolimus and paclitaxel)
Approved by FDA in 2003 and 2004
   80% of all stents deployed by 2005
Indications
   Stable coronary artery disease
   Lesions up to 32 mm in length
      Untreated native vessels
Ongoing data collection mandated by FDA
                 Definitions
Stent Thrombosis
   “Angiographic vessel occlusion and/or a STEMI
   in the target vessel distribution”
Timing
   Acute: within 24 hours
   Subacute: within 30 days
   Late: 30 days to one year
   Very Late: greater than one year
“Optimal Medical Therapy with or without PCI
    for Stable Coronary Artery Disease”
           NEJM 2007; 356:1003-16.
                  Methods
Sponsored by DVA/VAMC
Patients with stable CAD or stabilized CCS
 Class IV angina
   > 70% epicardial vessel (at least one vessel)
   Objective evidence of ischemia
Excluded
   Persistent Class IV symptoms, EF <30%, poor
   exercise stress test, refractory HR or shock
     Interventions / Outcomes
Random assignment
   PCI Vs. medical therapy
     Antiplatelets, lipid lowering therapy, anti-angina, and
      ACE or ARB
     Most patients received bare metal stents (BMS)
Primary Outcome: death of any cause and
 non fatal AMI
Secondary Outcomes: composite of death,
 AMI, CVA, and hospitalization for UA with
 positive markers
                    Analyses
Expected event rates:
   PCI (16.4%) and medical (21%)
Incorporated dropout and crossover
   2270 patients
Intention to treat
Survival analyses
   Kaplan-Meier, Cox Proportional Hazards
                    Results
2287 enrolled (1149 in PCI; 1138 medical)
   2/3 with multivessel CAD
   95% with objective ischemia
   60% with CCS Class II or II angina
Median follow-up of 4.6 years
   9% lost of follow-up
Revascularization (21% Vs 32%)
Approximately 72% angina free
                  Summary
Optimal medical therapy has similar
 outcomes to PCI based strategy as initial
 management of patients with stable
 coronary artery disease.
Less revascularization with PCI
Unknowns
   DES based PCI
   Prolonged use of anti-platelets
“Safety and Efficacy of Sirolimus- and
 Paclitaxel-Eluting Coronary Stents”


         NEJM 2007;356:998-1008.
                  Methods
Pooled analyses from:
   Four RCT comparing sirolimus DES vs. BMS
   Five RCT comparing paclitaxel DES vs. BMS
Databases provided by manufacturers
Unrestricted
Patient-level analyses
Follow-up: four years
   Acute, subacute, late stent thrombosis
                End Points
Stent thrombosis
Revascularization of target lesion
STEMI and NSTEMI
Mortality: overall, cardiac, and non cardiac
Composite
   Overall mortality or AMI (STEMI and NSTEMI)
   Overall mortality or STEMI
   Cardiac mortality or STEMI
                  Summary
Stent thrombosis higher in DES
   Small increase in absolute risk (0.35 to 0.6%)
   After 12 months
Less target revascularization with DES
Mortality and risk of STEMI/NSTEMI
 comparable
 “Long-Term Outcomes with Drug-Eluting
Stents versus Bare-Metal Stents in Sweden”

          NEJM 2007; 356:1009-1019.
                    Methods
Registry from Sweden (SCAAR)
   January 01, 2003 to December 31, 2004
   All patients receiving stents
      Complete follow-up data available

Twenty six centers
Independent of commercial funding
Longitudinal data (up to 12/31/2005)
   Hospitalizations for AMI and vital status
                   Analyses
Landmark Analysis
   6 months
Propensity Scores
   Patient characteristics
Multivariable model
                 Outcomes
Primary
   Composite of death or myocardial infarction
Secondary:
   Death
   Myocardial infarction
   Revascularization
   Restenosis
                    Results
Total of 19,771 patients
   37,750 stents
   24,215 procedures
   Breakdown:
      6,033 received DES
      13,738 received BMS

Regional variation in DES utilization
   0.6% to 41%
                  Summary
Effectiveness data set
   Unique patient population


Mortality increased in DES group
   One year after deployment
   Persisted in follow-up
“Outcomes and Complications Associated
   With Off-Label and Untested Use of
          Drug-Eluting Stents”

          JAMA 2007;297:1991-2000
                   Methods
Prospective Multicenter Registry
   140 medical centers (community and academic)
   PCI between 1/01/2005 to 6/31/2005
   Clinical outcomes assessed at hospitalization,
    30 days, 6 months, and 12 months
   Follow-up data
     Death, AMI, revascularization (PCI and CABG), and
      stent thrombosis
                  Definitions
Standard
   Discrete de novo lesions (< 30 mm) in native
   vessels of 2.5 to 3.5 cm in diameter
Off-label
   Restenotic lesion, length > 30 mm, vessel
   diameter < 2.5 cm or > 3.5 cm, bypass graft
Untested
   Left main, ostial, bifurcation, or totally occluded
   lesions
                Definitions
Standard clopidogrel
   Three months after sirolimus DES
   Six months after paclitaxel DES
Prolonged clopidogrel
   Beyond above
                    Outcomes
Effectiveness
   Target vessel repeat revascularization
Safety
   Composite of death, AMI, or stent thrombosis
     In-hospital
     30 day follow-up
     One year follow-up
                Summary
Greater risk of complications with off-label
 use of DES

Greater use of complications with untested
 use of DES
“Clopidogrel Use and Long Term Clinical
   Outcomes After DES Implantation”

              JAMA 2007;297:159-168
                  Methods
University base database
   BMS from 01/01/2000 to 07/31/2005
   DES from 4/01/2003 t0 7/31/2005
Baseline demographics, LHC data, medical
 history, and physical examination
Follow-up at 6 months, 12 months, and
 yearly thereafter (98% complete)
   Death and non fatal MI
   Use of aspirin and clopidogrel
                    Methods
Landmark Analyses
   Form of survival analysis
   Intermediate “event” is utilized
      Time: 6 months and 12 months after index PCI
Four groups
   DES with clopidogrel
   DES without clopidogrel
   BMS with clopidogrel
   BMS without clopidogrel
                 Methods
Follow-up of 24 months

Propensity scores for matching
   Demographics, CAD risk factors, h/o CHF/AMI,
   LHC findings, comorbidity index


Cox proportional hazards
Six Month Landmark Analysis
Twelve Month Landmark Analysis
Twelve Month Landmark Analysis
Six Month Landmark Analysis
                Summary
Prolonged therapy with dual anti-platelet
 therapy indicated for DES

Length of duration unknown

Comparable or better outcomes to BMS if
 combining DES with long term clopidogrel
                    Cases
Case #1
   Aggressive management of CAD risk factors
   including an exercise program might be a
   reasonable choice.
Case #2:
   While more data is being collected, use of
   clopidogrel might need to be prolonged
   indefinitely in patients with DES.
    What is the right question?
Should we ever deploy a stent?
   Yes in high risk ACS (BMS Vs. DES) or after
    STEMI with residual ischemia
   Maybe in stable CAD
     Suitable vessel
     Suitable lesion

In a patient with a DES, how should we
 manage it?
   Prolonged dual anti-platelet therapy
         “Other” Implications
Regulatory role of FDA
   When should pharmacologic agents and/or
   devices be approved for use?
Technology Assessment
   Should adoption of technology be regulated?
     By whom?