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Carotid Artery Disease Issues in Management Epidemiology of Stroke

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Carotid Artery Disease Issues in Management Epidemiology of Stroke Powered By Docstoc
					                          Carotid Artery Disease
                          Issues in Management


                       Mark A. Creager M.D.
                  Brigham and Women’s Hospital
                      Harvard Medical School




   Epidemiology of Stroke in the United
                 States

   • Prevalence
      • 4.8 million cases
   • Incidence
      • 700,000 new or recurrent strokes each year
   • Morbidity/mortality
      • Third leading cause of death
      • 1 of every 15 deaths (~273,000 deaths)
      • Stroke—a leading cause of long-term disability



American Heart Association. Heart Disease and Stroke Statistics—2006
Update.
                                                                                       2




                          Pathogenesis of Stroke
          Ischemic Stroke (80%)                        Hemorrhagic Stroke (20%)
 Atherothrombotic
 Cerebrovascular                                       Intracerebral
 Disease (20%)              Cryptogenic (30%)          Hemorrhage (70%)




                                 ?
 Lacunar (25%)
 (small vessel disease)   Cardioembolic (20%)          Subarachnoid Hemorrhage (30%)




Albers GW et al. Chest. 1998;119:683S-698S.
Albers GW Personal communication. February 27, 2003.
Rosamond WD et al. Stroke. 1999;30:736-743.
                                                                                       3
                                          Stroke Incidence in Northern
                                        Manhattan Stroke Study (NOMASS)

                                        300
 Age-adjusted Incidence/100,000/year




                                        250

                                        200
                                                                                                                                White
                                        150
                                                                                                                                Hispanic
                                        100                                                                                     Black

                                         50

                                          0
                                                                                 Men                     Women

                                        Sacco RL, et al. Am. J. Epidemiol. 147:260,1998
                                                                                                                                           4




                                                                             Incidence of Atherothrombotic
                                                                                    Brain Infarction

50 year follow-up data from the Framingham Heart Study
                                                                        20
                                                                        18
                                           Annual Incidence/1000/year




                                                                        16
                                                                                        Men
                                                                        14
                                                                                        Women
                                                                        12
                                                                        10
                                                                         8
                                                                         6
                                                                         4
                                                                         2
                                                                         0
                                                                              35-44    45-54   55-64    65-74   75-84   85-94
                                                                                                  Age
Wolf, PA, Kannel WB. Epidemiology of Cerebrovascular Disease,
in Creager et al. Vascular Medicine, 2006                                                                                                  5




                                          Outcomes After Ischemic Stroke

                                       Stroke Recurrence                                           Functional Disability
                                       30 day       3%-10%                                         • 24%-53% of stroke
                                       1 year       5%-14%                                           survivors with complete
                                       5 year      25%-40%                                           or partial dependence
                                       Mortality
                                                                                                   Quality of Life
                                       30 day                                     8%-20%           • 27% decrement in mean
                                       1 year                                    15%-25%             quality of well-being
                                       5 year                                    40%-60%             score at 6 months
                                                                                                   Dementia or Cognitive
                                                                                                     Decline
Sacco RL. Neurology. 1997;49(suppl 4):S39-S44.
                                                                                                   • 34% at 52 months                      6

                                                                                                     poststroke
         Sites of Cervical and Cranial
                Atherosclerosis




                                                           7




  Patterns of Findings According to
           Stroke Location

• Left ICA-MCA
  • Right hemiparesis, hemisensory loss, hemianopia,
    aphasia
• Right ICA-MCA
  • Left hemiparesis, hemisensory loss, hemianopia, left
    neglect, abnormal drawing, abnormal visual-spacial
    abilities
• Left PCA
  • Right hemianopia, alexia without agraphia, right
    hemisensory symptoms
• Right PCA
  • Left hemianopia, left hemisensory symptoms
                                                           8




              Lacunar Infarctions

• Weakness of face, arm, and leg on one
  side of the body
• Sensory symptoms of face, arm, and leg
  on one side of the body
• Weakness and ataxia on one side of the
  body
• Dysarthria and clumsiness of one hand


                                                           9
                      Differential Diagnosis of
                          TIAs and Stroke
    Common Disorders                  Focal Symptoms                    Nonfocal Symptoms
    TIAs                              ++++                              Occasionally
    Seizures                          ++                                ++
    Migraine                          ++++
    Syncope                                                             ++++
    Less Common
    Conditions
    Vestibulopathy                    ++                                ++
    Metabolic                         +                                 +++
    “Tumor Attacks”                   +++                               +
    Multiple Sclerosis                ++++
Caplan, LR. Cerebrovascular Disease: Clinical Presentation. In Creager et al. Vascular Medicine, 2006   10




               Prevalence of ≥50% Carotid Stenosis
                                 The Framingham Study


        10

           8

           6
 %         4

           2

           0

                        Men at 75 yrs           Women at 75 Yrs             Age 50

                                     Fine-Edelstein JS, Neurology. 1994; 44: 1046
                                                                                                        11




               Prevalence of Carotid Artery Disease
                             Cardiovascular Health Study


      Prevalence of extracranial carotid atherosclerosis assessed by
                 ultrasonography in men aged >65 years.

               8
               7
               6
               5
      %        4
               3
               2
               1
               0
                       65-69              70-74             75-79             80-84

                                            50-74%       75-99%
                                                             O’Leary, DH. Stroke 1992:23:1752           12
              Prevalence of Carotid Artery Disease
                                                             Cardiovascular Health Study


Prevalence of extracranial carotid atherosclerosis assessed by
         ultrasonography in women aged >65 years.

                                                  6
                                                  5
                                                  4
 %                                                3
                                                  2
                                                  1
                                                  0
                                                           65-69        70-74         75-79          80-84

                                                                          50-74%    75-99%
                                                                                              O’Leary, DH. Stroke 1992:23:1752
                                                                                                                             13




Risk of an Ipsilateral Stroke at Five Years
                                                                   No Symptoms
     Risk of Ipsilateral Stroke at 5 Years (5%)




                                                                   Symptoms
                                                      30

                                                      25

                                                      20

                                                      15

                                                      10

                                                       5

                                                       0
                                                             0     <50 50-59 60-74 75-94 95-99 100
                                                                   Percent Stenosis on Angiography
     Inzitari, D. et al. N Engl J Med 2000;342:1693-1701
                                                                                                                             14




     Mechanisms of Stroke in Patients with
           Carotid Artery Stenosis




                                                                                                                             15
        Ruptured Carotid Plaque




                                                              16




       Cardiovascular Health Study
Incidence of MI or Stroke According to Carotid IMT
           n = 4476 subjects without cardiovascular disease
           65 years of age or older followed for 6.2 years.




  O'Leary D et al. N Engl J Med 1999;340:14-22
                                                              17




Maximum Carotid Plaque Thickness and
Ten Year Risk of Cardiovascular Events




Rundek, T. et al. Neurology 2008;70:1200-1207
                                                              18
Association between Progressive Carotid Artery
          Disease and Risk for MACE




      Sabeti, S. et al. Stroke 2007;38:2887-2894                                    19




 Diagnostic Tests for Carotid Stenosis and
                  Stroke

• Carotid Stenosis
  • Duplex ultrasonography
  • MR angiography
  • CT angiography
  • Conventional angiography
• Stroke
  • CT
  • MR imaging


                                                                                    20




   Assessment of Carotid Disease by
          Duplex Ultrasound




   Common Carotid Artery        Internal Carotid Artery   External Carotid Artery
                                                                                    21
 Duplex Ultrasound: Calcified Plaque in the
          Internal Carotid Artery




                                         Calcified Plaque




         Right Internal Carotid Artery


                                                            22




          Color Assisted Duplex
            Ultrasonography:
     Internal Carotid Artery Stenosis




                                                            23




Color Assisted Duplex Ultrasonography:
    Internal Carotid Artery Stenosis




                                                            24
Magnetic Resonance Imaging
   of the Carotid Artery




A                                   B

                                                           25




Computed Tomographic Angiogram
    of the Carotid Arteries




       www.medical.philips.com/.../ carotidstenosis2.jpg   26




      Digital Substracton Angiogram:
    Left Internal Carotid Artery Stenosis




                                                           27
            Pharmacologic Therapies to
                 Prevent Stroke

    • Lipid lowering drugs
         • Statins
    • Antihypertensive drugs
    • Platelet inhibitors
         • Aspirin
         • Aspirin + dipyridamole
         • Clopidogrel



                                                                               28




      Relationship between LDL Reduction with
              Statins and Risk of Stroke
• Meta-analysis of 26
trials that included over
90,000, patients.

• Baseline mean LDL
concentration ranged
from 124 to 188 mg/dl and
averaged 149 mg/dl.

• Statins reduced the risk
of all strokes by ~ 21%

• For each 10% LDL-C
reduction, the risk of all
strokes decreased by
15.6%


                             Amarenco, P. et al. Stroke 2004;35:2902-2909
                                                                               29




                     Statins and Risk of Stroke



 •Prospective meta-
 analysis of data from
 90,056 participants in
 14 randomized trials

 •Statins were
 associated with a
 19% reduced risk of
 ischemic stroke




                                     Baigent, C. Lancet. 2005; 366: 1267-78.   30
   SPARCL: High-dose statin treatment
      reduces fatal/nonfatal stroke
            4731 subjects with previous stroke or TIA randomly
               assigned to atorvastatin (80mg/d) or placebo.
            16                                                              NNT = 46
                     16% RRR*                                               patients
                     HR 0.84 (0.71–0.99)           Placebo                  for 5 years
                     P = 0.03
            12
 Fatal/
nonfatal                                                Atorvastatin
            8
 stroke
  (%)

            4


            0
                 0       1         2        3       4         5        6
                             Time since randomization (years)

*Adjusted                            SPARCL Investigators. N Engl J Med. 2006;355:549-59.
                                                                                            31




            Lipid Lowering Therapy for TIA or
                    Ischemic Stroke

                              Treatment with a HMG coenzyme-A reductase
       I IIa IIb III          inhibitor (statin) medication is indicated for
                              patients with ischemic stroke or TIA to achieve
                              LDL cholesterol of less than 100 mg/dl and LDL-
                              C of <70 mg/dL for very-high-risk persons with
                              multiple risk factors.




 AHA/ASA Guidelines for Prevention of Stroke in Patients With Ischemic
 Stroke or Transient Ischemic Attack Circulation 2006;113;409-449


                                                                                            32




             Antihypertensive Therapy and Stroke
                  Reduction in Clinical Trials


        Meta-analysis of Placebo-Controlled Trials in Hypertension




                                            Psaty et al., JAMA., 1997
                                                                                            33
           ACE Inhibition Decreases Stroke in
                 a High Risk Population
       9297 patients with vascular disease or diabetes plus an
       additional risk factor randomized to ramipril or placebo




 1.5% Absolute Reduction

 34% Relative Reduction




 Bosch J. BMJ 2002; 324:699                                                      34




       ACE Inhibition Prevents Recurrent Stroke
                             The Progress Trial



6105 subjects with previous
stroke randomly assigned to
perindopril (n=3051) or
placebo (n=3054)




                            PROGRESS Collaborative Group. Lancet 2001:358; 1033
                                                                              35




        The PRoFESS Study: Telmisartan for
                Recurrent Stroke
                                 Primary Endpoint: Recurrent Stroke

• Multicenter trial involving
20,332 patients with an
ischemic stroke

• Randomized to telmisartan
(80 mg daily) or placebo.

• 8.7%) in the telmisartan
group and 9.2% in the
placebo group had a
subsequent stroke (HR =
0.95; CI, 0.86 to 1.04)

                                Yusuf S et al. N Engl J Med 2008;359:1225-1237
                                                                                 36
                             Antihypertensive Therapy for TIA or
                                      Ischemic Stroke

                             I IIa IIb III
                                               Antihypertensive treatment is recommended for
                                               prevention of recurrent stroke


                             II IIa IIb III
                                    IIb III
                                               The optimal drug regimen remains uncertain;
                                               however, the available data support the use of
                                               diuretics and the combination of diuretics and
                                               an ACEI .

  AHA/ASA Guidelines for Prevention of Stroke in Patients With Ischemic
  Stroke or Transient Ischemic Attack Circulation 2006;113;409-449


                                                                                                    37




                                    Effect of Antiplatelet Therapy
                                    in Patients with TIA or Stroke

                             N = 18 trials         25      Odds Reduction = 22%

                                                   20

                      Patients with                15
                      Stroke, MI or
                     Vascular Death                10
                           (%)
                                                    5

                                                    0
                                                             Control          Antiplatelet
                                                             n = 5870          Therapy
                                                                               n = 5837

                                              Antiplatelet Trialists’ Collaboration. BMJ,1994       38




                                Aspirin & Dypyridamole Decreases
                                         Stroke after TIA
                                   European/Australasian Stroke Prevention in
                                       Reversible Ischaemia Trial (ESPRIT)
2739 patients within 6 months of TIA or minor CVA taking ASA (30–325 mg QD)
randomized to dipyridamole (200 mg twice daily) or placebo. Primary outcome
was vascular death, non-fatal CVA, non-fatal MI, or major bleeding complication
   Events at 3.5 years (%)




                              24

                              18                                        *
                              12
                                                   16%           13%
                               6

                               0

                                              Aspirin   Aspirin-Dypyridamole
                                                                                                    39
                                                        Esprit Study Group, Lancet 2006; 367: 1665–73
                The PRoFESS Study:
    Aspirin and Extended-Release Dipridamole vs
           Clopidogrel for Recurrent Stroke
                                 Primary Endpoint: Recurrent Stroke
•Patients   with an
ischemic stroke
Randomized to 25 mg
of aspirin plus 200 mg
of extended-release
dipyridamole twice
daily or to 75 mg of
clopidogrel daily.

•Recurrent stroke
occurred 9.0%
receiving ASA-ERDP
and in 8.8% receiving
clopidogrel (HR =
1.01; 95% CI 0.92 to
1.11).
                               Sacco R et al. N Engl J Med 2008;359:1238-1251   40




 Aspirin vs. Warfarin on Recurrent Ischemic Stroke
    or Death in Patients with Ischemic Stroke




Mohr, J.P. et al. The Warfarin Aspirin Recurrent Stroke Study
N Engl J Med 2001;345:1444-1451                                                 41




  Antiplatelet Therapy for TIA or Ischemic Stroke


                         For patients with noncardioembolic ischemic
        I IIa IIb III    stroke or TIA, antiplatelet agents rather than oral
                         anticoagulation are recommended to reduce the
                         risk of recurrent stroke and other cardiovascular
                         events.

       I IIa IIb III
                         Aspirin (50 to 325 mg/d), the combination of
                         aspirin and extended release dipyridamole, and
                         clopidogrel are all acceptable options for initial
                         therapy

  AHA/ASA Guidelines for Prevention of Stroke in Patients With Ischemic
  Stroke or Transient Ischemic Attack Circulation 2006;113;409-449

                                                                                42
      Carotid Artery Revascularization
                 Carotid Endarterectomy




                                                                   43




   Carotid Endarterectomy Trials: Symptomatic
                 Carotid Stenosis


     • North American Symptomatic
       Carotid Endarectromy Trial
     • European Carotid Surgery Trial
     • Veterans’ Administration
       Cooperative Studies Program




                                                                   44




       NASCET: Any Ipsilateral Stroke

           1.0
                                           Surgery
           0.9                                              91%

Proportion 0.8                                         RRR = 65%
  Event                                    Medicine
           0.7                                              74%
   Free
           0.6 Surg. 250      206    160        112        52
                 Med. 233     174    118        72         35
           0.5
                 0    6      12     18     24         30
                            Month of Study
        NASCET Collaborators. New Engl. J. Med., 1991
                                                                   45
    Risk of Ipsilateral Ischemic Stroke After CEA
        With Carotid Stenosis of 70% to 99%

          Age Group                     Absolute RR              NNT
          >75 Years                            28.9%             3.47

          65-74 Years                          15.1%             6.62

          ≤65 Years                            9.7%              10.31




        Alamowitch S et al, for the NASCET Group. Lancet. 2001;357:1154-
        1160.                                                                   46




  ECST:Ipsilateral Ischemic Stroke, Disabling
                    or Fatal

                    100                                Surgery
                                                                    98.9%
                                                       No Surgery
                                                                    91.6%
  Event Free 90                   P < 0.0001
     (%)

                     80
                                 5/455 allocated to surgery
                                 27/323 allocated to no surgery

                          0 1          2        3
                             Years of Follow-up
         ECST Trialists. Lancet, 1991
                                                                                47




     Symptomatic Carotid Endarterectomy (CEA):
        Pooled Data From Randomized Trials

                                                         ARR
     Stenosis                         n                 (%)          P Value
          <30%                     1746                 -2.2             .05

     30% to 49%                    1429                 3.2                .6

     50% to 69%                    1549                 4.6              .04

    >70% to 99%                    1095                 16.0            <.001


Rothwell PM et al. Lancet. 2003;361:107-116.
                                                                                48
          Carotid Endartectomy for
        Asymptomatic Carotid Stenosis

 • Asymptomatic Carotid Atherosclerosis
   Study
 • VA Cooperative Study Group
 • Asymptomatic Carotid Surgery Trial




                                                                                                  49




         ACAS: Ipsilateral Stroke or
        PerioperativeDeath or Stroke
                                                   1.0
                                                                           Surgery
                           Proportion Event Free




•Patients with                                                                            94.9%
asymptomatic carotid                               0.9
artery stenosis >60%                                                                      89.0%
                                                                           Medicine
in diameter
                                                         RRR = 53%
                                                   0.8
•1662 patients
randomized to
surgery or no surgery                              0.7

•Median follow-up =                                  0    1      2     3      4       5
2.7 years
                                                              Years of Follow-up

   Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
   JAMA. 1995;273:1421-1428.
                                                                                                  50




               ACST: Any Stroke or Death
 • 3210 patients with >60% stenosis




 MRC Asymptomatic Carotid Surgery Trial Collaborative Group, Lancet, 2004;363:1491
                                                                                                  51
  Medical Intervention for Prevention of Ipsilateral Stroke
  Associated With Asymptomatic Severe Carotid Stenosis
      Average annual stroke (+/-TIA) rates by publication year




Abbott, A. L. Stroke 2009;40:e573-e583
                                                                 52




             Proven Indications for Carotid
                   Endarterectomy

  For symptomatic patients with a surgical
    risk <6%
        • Single or multiple TIAs within a 6 month
          period or crescendo TIAs in the presence of a
          stenosis >70%
        • Mild stroke within a 6 month period in the
          presence of a stenosis >70%

            Ad Hoc Committee, AHA, “Guidelines for
            Carotid Endarterectomy” Circulation,
            1995
                                                                 53




     Acceptable Indications for Carotid
             Endarterectomy
              For asymptomatic patients with a
                surgical risk <3%
                    • The presence of a stenosis >75%,
                      irrespective of contralateral artery
                      status
              For asymptomatic patients with a
                surgical risk 3-5%
                   • The presence of a stenosis >75%, with a
                     contralateral internal carotid artry
                     stenosis >75%
                  Modified from Ad Hoc Committee, AHA,
                  “Guidelines for Carotid Endarterectomy”
                  Circulation, 1995

                                                                 54
                       Carotid Stenting:
                      An Emerging Option




      PRE        POST                                    PRE       POST
         R CAROTID                                         L CAROTID

                                                                                        55




 Stenting and Angioplasty With Protection in Patients at
     High Risk for Endarteractomy (SAPPHIRE) Trial

  • Comparison of patients with carotid stenosis treated
    with carotid stents versus carotid endarterectomy

  • Patients eligible if they were asymptomatic with 80%
    stenosis by ultrasound or symptomatic with >50%
    stenosis and at least one high-risk feature

  • High risk as defined by cardiopulmonary comorbidities,
    prior neck irradiaiton or radical neck surgery,
    restenosis following carotid endarterectomy, age >80
    years

  • 307 patients were enrolled in the trial. 156 had carotid
    stenting, 151 had carotid endarterectomy
                                  Yadav, J. S. et al. N Engl J Med 2004;351:1493-1501
                                                                                        56




      SAPPHIRE: Death, MI, Stroke at 30 days;
     Ipsilateral Stroke or Death 31 Days to 1 year
 •   Asymptomatic patients with 80% stenosis or symptomatic with
     >50% stenosis and at least one high-risk feature
 •   High risk defined by cardiopulmonary comorbidities, prior neck
     irradiation or radical neck surgery, restenosis following CEA, or age
     >80y




                          CAS = 156
                          CEA = 151
                                                 12.2 vs 20.1%,
                                                 p=0.004 for noninferiority




Yadav, J. S. et al. N Engl J Med 2004;351:1493-1501                                     57
    Endarterectomy versus Stenting in Patients with
     Symptomatic Severe Carotid Stenosis (EVA-3S)
    •   Inclusion Criteria: Hemispheric or retinal TIA or a nondisabling stroke
        within 120 days; 60 to 99% ipsilateral carotid artery stenosis
    •   1o Endpoint: Risk of Stroke or Death within 30 Days after Endarterectomy
        or Stenting




   Criticized because of relative inexperience of carotid interventionalists
   as compared with vascular surgeons

 Mas JL et al. N Engl J Med 2006;355:1660-1671
                                                                                                 58




           EVA 3-S: Incidence of Primary Outcome
                     Events at 6 Months




    Mas JL et al. N Engl J Med 2006;355:1660-1671


                                                                                                 59




  Stent-Supported Percutaneous Angioplasty of the
 Carotid Artery versus Endarterectomy (SPACE) Trial
 Patients with symptomatic carotid artery stenosis within 180 days of TIA or moderate stroke
 Primary endpoint: Ipsilateral stroke (ischemic or intracerebral bleed) or death from time of
 randomization to 30 days after the procedure
                                               N = 595
                                               N = 605


                                               CAS = 6—84% vs 6—34% with CEA
                                               (p=0.09 for noninferiority)




•Criticized because a distal protection device was used in only 27% of patients undergoing CAS
Ringleb PA, et al. Lancet. 2006;368:1239-47.                                                     60
     CREST (Carotid Revascularization
    Endarterectomy versus Stent Trial)

• CREST contrasts the relative efficacy of
  carotid endarterectomy (CEA) and carotid
  angioplasty-stent (CAS) in preventing primary
  outcomes of stroke, myocardial infarction, or
  death during a 30-day periprocedural period,
  or ipsilateral stroke over the follow-up period
  extending up to 4 years.




                                                    61




Secondary Prevention for Carotid Artery Disease
           Get with the Guidelines




                         Extracranial Carotid
                         and Vertebral Artery
                               Disease



                          Coming Soon
                                                    62

				
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