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					     The Guidelines:
How Can They Be Improved?

           Peter Berger MD
     Interventional Cardiologist
 Director, Center for Clinical Studies
           Geisinger Clinic
             Danville, PA
Recommended Aspirin Dose After
PCI
• The updated 2007 ACC/AHA/SCAI PCI
  guidelines recommend:
 – 162 - 325 mg for 1 month after BMS, 3
   months after sirolimus-eluting stents, 6
   months after paclitaxel-eluting stents
 – 75 - 162 mg daily thereafter




             King III SB, et al. J Am Coll Cardiol. 2008;51:172-209.
Aspirin Dose and Vascular Events in
High-Risk Patients

                                                 OR*
  Daily Aspirin Dose         No. of Trials              (%) Odds Ratio
    500–1500 mg                34                  19
    160–325 mg                 19                  26
    75–150 mg                  12                  32
    <75 mg                       3                 13
    Any aspirin                65                  23                                  P = 0.0001

                                                 0          0.5          1.0           1.5     2.0


                                                 Antiplatelet Better           Antiplatelet Worse

                       Antithrombotic Trialists’ Collaboration. BMJ. 2002;324:71-86.
                                                         Reproduced with permission.
Aspirin Dose and Major Bleeding
Post Hoc Analysis Of 192,036
Pts Enrolled In 31 Controlled Trials
          7
          6
                                                        P<0.005
          5
 Bleeding 4
                                                                    2.29
   Rate
    (%)   3
               1.56                     1.54
                                                                         *
          2
          1
          0
              <100 mg             100-200 mg                     >200 mg

                                Aspirin Dose

                 Serebrauny V, et al. Am J Cardiol. 2005;95:1218-1222.
CURE: Aspirin Dose and Outcome
          CV Death, MI, Stroke                                       Major Bleeding
15                                             13.6 5                                           4.9


               10.5                                    4                                              3.7
                        9.5 9.8          9.8                                        3.4
10       8.6                                                     3
                                                       3                                  2.8

%                                                      2
                                                                      1.9
    5
                                                       1

    0                                                  0
        ≤ 100 mg      101-199 mg       ≥ 200 mg               ≤ 100 mg          101-199 mg      ≥ 200 mg
        (N = 5320)     (N = 3109)      (N = 4110)

               ASA/Clopidogrel                      ASA/Placebo
                                    Peters RJ, et al. Circulation. 2003;108:1682-1687.
 CHARISMA
 Aspirin Dose and Efficacy
        10                                                                      N = 15,603
                                                              P = 0.14
         8                  P = 0.07


                                              7.3%                           7.6%
CV Death, 6
 MI, or
                6.7%
 Stroke
   %      4


         2


         0
              < 100mg                        100mg                          > 100mg
              N = 7180                      N = 4961                        N = 3454
                                         Aspirin Dose
                     Steinhubl S, et al. Circulation. 2006;114:2490-2497.
 CHARISMA: Aspirin Dose and Safety
  GUSTO Severe Bleed

      5
      4
 %    3                               P = NS
      2
      1                                         1.5%                              1.8%
                 1.4%
      0
                < 100mg                     100mg                                > 100mg
                                        Aspirin Dose
Clopidogrel-treated pts:
                                     100 mg                    > 100mg                  P value
  CV death/MI/CVA                       6.4                        8.4                    0.010
  GUSTO Severe                          1.5                        2.2                    0.056
  GUSTO Severe/Moderate                 3.5                        4.4                    0.077

                          Steinhubl S, et al. Circulation. 2006;114:2490-2497.
ACC/AHA/SCAI 2005 Guideline
Update for PCI
Class IIb: In patients in whom subacute
thrombosis may be catastrophic or lethal
(unprotected left main, bifurcating left
main, or last patent vessel), platelet
aggregation studies may be considered
and the dose of clopidogrel increased to
150 mg per day if less than 50%
inhibition of platelet aggregation is
demonstrated. (Level of Evidence: C)
Level of Evidence C: Only consensus opinion of experts, case studies, or standard-of-care.

                                Smith S, et al. Circulation. 2006;113:156-175.
Recommended Duration of
Clopidogrel After PCI With a DES
The updated 2007 ACC/AHA/SCAI PCI
 guidelines recommend:
• For all post-PCI stented pts receiving a
  DES, clopidogrel 75 mg daily should be
  given for at least 12 months if pts are
  not at high risk of bleeding.




           King III SB, et al. J Am Coll Cardiol. 2008;51:172-209.
 Cumulative Incidence of Definite ST in
 8146 DES Patients During a 4-Year
 Follow-Up Period
           6
                                                                               5.7%
                                                                               Definite and
           5                                                                   probable ST

           4
Cumulative                                                                     3.3%
incidence, 3                                                                   Definite ST
     %
           2


           1


           0
               1             2                    3                    4

                     Time since PCI in years

                   Wenaweser P, et al. J Am Coll Cardiol. 2008;52:1134-1140.
                                                Reproduced with permission.
  CHARISMA: Documented CV Disease
  Population Secondary Efficacy Results

Endpoints                           Clopidogrel             Placebo              RR           P
                                       +ASA                  + ASA            (95% CI)      value
                                     (n=6062)              (n=6091)
CV Death, MI, Stroke                     420 (6.9)            480 (7.9) 0.88(0.77, 0.998)   0.046
CV Death, MI, Stroke, Hosp           1066 (17.6)          1169 (19.2) 0.91 (0.83, 0.98)      0.02
All-Cause Mortality                      278 (4.6)            306 (5.0) 0.91 (0.78, 1.07)    0.27
Cardiovascular Mortality                 172 (2.8)            191 (3.1) 0.90 (0.74, 1.11)    0.34
Myocardial Infarction                    145 (2.4)            165 (2.7) 0.88 (0.71, 1.10)    0.27
Ischemic Stroke (fatal or not)           145 (2.4)            172 (2.8) 0.85 (0.68, 1.06)    0.14
Stroke (fatal or not)                    167 (2.8)            200 (3.3) 0.84 (0.68, 1.03)    0.09
Hospitalization                        720 (11.9)           803 (13.2) 0.89 (0.81, 0.99)     0.03




                           Wang TH, et al. Eur Heart J. 2007; 28:2200-2207.
CHARISMA: Documented CV Disease
Population Safety Results

Safety Outcome - N (%)        Clopidogrel            Placebo              RR         P
                                 + ASA                + ASA            (95% CI)      value
                               (n=6062)             (n=6091)

GUSTO Severe Bleeding             95 (1.6)            84 (1.4)            1.14         0.39
                                                                      (0.85, 1.52)

  Fatal                           19 (0.3)            13 (0.2)            1.47         0.28
                                                                      (0.73, 2.97)
  Primary ICH                     19 (0.3)            21 (0.3)            0.87         0.65
                                                                      (0.47, 1.60)
GUSTO Moderate Bleeding         128 (2.1)            79 (1.3)             1.63       <0.001
                                                                      (1.23, 2.15)




                   Wang TH, et al. Eur Heart J. 2007; 28:2200-2207.
Summary

• Given these unknowns:
  – True duration of risk for DES thrombosis
  – Optimal duration of clopidogrel to reduce
    that risk
• And that:
  – > 12,000 pt CHARISMA subset suggests
   benefit > 1 yr of clopidogrel


  I would not discontinue clopidogrel in
               high risk pts
Summary

• Many areas of uncertainty remain
• The guidelines try to be evidence based
• Controversy remains

				
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