Docstoc

Clopidogrel

Document Sample
Clopidogrel Powered By Docstoc
					Disease in any vascular bed increases the lifetime risk of
            multiple atherothrombotic events

History                     Increased risk of MI                   Increased
                                                                 risk of stroke
MI                                  5-7 X                            3-4 X
                                  greater risk                    greater risk
                               (includes death)                  (includes TIA)
Ischemic Stroke                     2-3 X                              9X
                                 greater risk                     greater risk
                            (includes angina and
                                sudden death)
PAD                                   4X                             2-3 X
                                greater risk                      greater risk
                      (includes only fatal MI and other          (includes TIA)
                       coronary heart disease death)



                  Circulation 1994; 89: 1333-1363; J Cardiovasc Risk 1994; 1:333-339;
                               Arch Neurol 1992; 42:857-863; NEJM 1992; 326: 381-386
CAPRIE trial: Risk reduction in specific subgroups


                                           Stroke subgroup   PAD subgroup         MI subgroup
                                      0
  Risk reduction in event rate (%)




                                      -5

                                     -10        -7.3                                  -7.4

                                     -15

                                     -20

                                     -25                        -23.3
                                                                            Lancet 1996; 348: 1329-1339
                                      CURE study: Results

                           0.14
                                                                                  20%
                           0.12
CV death, nonfatal MI or


                                             Placebo
                           0.10
      stroke (%)



                                                               Clopidogrel
                           0.08

                           0.06

                           0.04                        P<0.001

                           0.02

                           0.00
                                  0      3           6           9           12
                                             Months of follow-up

                                                                       NEJM 2001; 345:495-502
                                CURE Trial: Results (Contd.)


                                               At 24 hours
                          2.5                                           34%
                                       2.1%
CV death, nonfatal MI,
stroke or refractory or




                           2
   severe ischemia




                                                              1.5%
                          1.5

                           1

                          0.5

                           0
                                  Placebo + aspirin    Clopidogrel + aspirin
                                                              NEJM 2001; 345:495-502
                                 Risk reduction (%)




                          -35
                                -30
                                      -25
                                            -20
                                                    -15
                                                          -10
                                                                -5
                                                                     0
                                                                          CV death,
                                                                         nonfatal MI,
                                                                          stroke or




                                                  -14
                                                                          refractory
                                                                          ischemia



                                                                         MI




                                      -23
                                                                            Refractory
                                                                         ischemia during




                          -32
                                                                              initial
                                                                          hospitalisation



                                                                         Revascularisation
                                                          -8




                                                                            procedure




                                                                         Stroke
                                                  -14
                                                                                             CURE trial: Results (Contd.)




                                                                         Heart failure
                                            -18




NEJM 2001; 345: 494-502
                                     CURE Trial: Results (Contd.)


                                                                                                                     18%
                       2.5
                                                43%                               8        7.2%
                                2%                                                7
thrombolytic therapy




                                                         % patients requiring
% patients requiring




                                                         GP IIb/IIIa inhibitors
                        2                                                                                     5.9%
                                                                                  6
                       1.5                                                        5
                                            1.1%                                  4
                        1                                                         3
                                                                                  2
                       0.5
                                                                                  1
                        0                                                         0
                             Placebo +   Clopidogrel +                                Placebo + aspirin   Clopidogrel +
                               aspirin      aspirin                                                          aspirin


                                                                                         NEJM 2001; 345:495-502
              PCI-CURE study: Results


Primary outcome (cardiovascular death, myocardial infarction,
             urgent revascularisation) events

Number of days      Placebo      Clopidogrel           Risk
  after PCI         (n=1345)      (n=1313)           Reduction
      <2              3.0%           2.4%                20%
      <7              4.4%           3.0%                31%
      < 14            5.4%           3.7%                33%
      < 30            6.4%           4.5%                30%

                                            Lancet 2001; 358: 527-533
                                 PCI-CURE study: Results

                 0.15                             Placebo
                                                                         31%
CV death or MI




                 0.10
                                                        Clopidogrel         A= median time from
                                                                            randomisation to
                                                                            percutaneous
                 0.05                                                       coronary intervention.
                                                   p=0.002
                                                                            B = 30 days after
                                                                            median time of PCI.

                 0.00
                        010 40    100         200         300         400
                                        Days of follow-up
                         A B
                                                                      Lancet 2001; 358: 527-533
                                       Clopidogrel v/s Ticlopidine in
                                            Coronary Stenting

                                               Ticlopidine (n=827)       Clopidogrel (n=500)

                          1.8         Dose: Aspirin >325mg + Clopidogrel 300 mg (loading), 75mg (14 days)
                                                                     OR                                     1.6
Event rate, 30 days (%)




                          1.6
                                          Aspirin + Ticlopidine 500 mg (loading), 250 mg bd (14 days)
                          1.4
                          1.2   1.1
                            1                                                                                     0.8
                          0.8                                          0.7
                          0.6                      0.5                                     0.5
                                      0.4                                                        0.4
                          0.4                                                0.2
                          0.2                             0
                            0
                                 Death            Myocardial             Stent         Repeat PTCA or       Any event
                                                  infarction          thrombosis           CABG
                                                  (nonfatal)
                                                                                                 JACC 1999; 34:1891-1894
                                  CLASSICS: Results
Occurrence of composite of major peripheral or bleeding complications, neutropenia, thrombocytopenia or
         early discontinuation due to noncardiac event (skin disorder, GI disorder, allergy, etc)
                                                    P=0.005

                                                P=0.001
   10                       P=0.194
    9
                  9.1
    8
                                                   P=0.043
    7
    6                                     6.3
  %
    5
    4                                                                                     4.6
    3
                                                                  2.9
    2
                N=31/340                N=11/335
    1                                                          N=10/345                N=31/680
    0
          Ticlopidine 250 mg      Clopidogrel 75 mg       Clopidogrel 300/75      Clopidogrel Total
                  bid                    od                     mg od
                                                                          Circulation 2000; 102:624-629
Clopidogrel in patients with prior bypass surgery
               (CAPRIE substudy)
             A
                        10                               9.7%
                         9                                             43%
                         8                               8.1%
   Vascular death (%)

                         7
                         6
                         5
                         4       Aspirin
                         3
                         2                 Clopidogrel
                         1                        p = 0.03
                         0
                             0    6 12 18 24 30 36
N=1480                             Months of Follow-up
                                                         Circulation 2001; 103: 363-368
Clopidogrel in patients with prior bypass surgery
               (CAPRIE substudy)
                                                  B   50
                                                                                                                    46.1%
                                                      45

         rehospitalisation for ischemia or bleeding
                                                                                                                            31%
                                                      40
              Vascular death, MI, stroke or

                                                                                                                    36.7%
                                                      35

                                                      30

                                                      25
                                                               Aspirin
                                                      20

                                                      15                        Clopidogrel

                                                      10
                                                                                                   p = 0.001
                                                       5

                                                       0
                                                           0      6        12      18         24     30        36
                                                                         Months of Follow-up
N=1480                                                                                                    Circulation 2001; 103:363-368
                  Clopidogrel vs. Aspirin
   More effective in ADP-mediated platelet aggregation (stenosed
    arteries or sites of endothelial injury)
   Greater reduction in vascular events, as shown by CAPRIE trial
   Lesser hospitalisations for ischemic events
   10-45% patients may be “aspirin-resistant”
   Many patients may not tolerate aspirin (allergy - aspirin triad, GI
    intolerance, peptic ulcers)
   Lesser drug interactions (none seen with acetazolamide,
    anticonvulsants, beta blockers, diuretics, methotrexate, oral
    hypoglycemics and uricosuric agents)
   Lesser incidence of GI hemorrhage
   No interactions with ACE inhibitors
   No interaction with alcohol, unlike aspirin
               Clopidogrel vs Ticlopidine
   Six times more potent
   Faster onset of action (within 24 hours as compared to 3 days)
   Better tolerability profile
    - Lesser incidence of severe neutropenia (0.04% vs 2.5%) and
    TTP (4 cases per million patients vs. one case per 2000 to 4000
    patients)
    - Routine hematologic monitoring not essential
    - Does not cause increase in cholesterol levels
   Once daily regimen
   Lesser drug interactions (none seen with antipyrine, antacids,
    cimetidine, digoxin or theophylline)
   More economical
      Clopidogrel: Indications & Dosage

 Prevention of vascular events in patients with
  atherosclerosis documented by recent stroke, recent
  MI or established PAD
  75 mg once daily
 Acute coronary syndrome
  300 mg (loading dose) followed by 75 mg once daily
 PTCA (with or without stenting)
  300 mg (loading dose) followed by 75 mg once daily
 Prior bypass surgery
  75 mg once daily

				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:84
posted:3/30/2008
language:English
pages:15