Journal Club

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Journal Club
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Clinical ScenarioA 65 year old gentleman with
CVA 2005, ischemic stroke L parietal lobe with
mild residual weakness of R LE Poorly
differentiated Squamous cell Ca Lung, s/p LLL and
partial resection of L upper lobe 2005 with
positive margins, s/p Chemotherapy with 4 cycles
of Taxotere and Carboplatin Poorly controlled
HTN and who is Obese presents to the clinic for
a follow up visit.History Question of
Medication Non AdherenceNo change in baseline
SOB, lifestylePE Remarkable for High
BPMedications ASA 325 mg, HCTZ 25, Amlodipine
10, Doxazosin 1 mg, Tiatropium and Albuterol
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Clinical Question Is the combination of
Clopidogrel and Aspirin superior to Aspirin alone
in reducing Mortality or in decreasing risk of
Stroke in a 65 yr old obese gentleman s/p
Ischemic stroke and with poorly controlled HTN
and Metabolic syndrome
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Relevant Study for searchAspirin and
clopidogrel compared with clopidogrel alone after
recent ischaemic stroke or transient ischaemic
attack in high-risk patients (MATCH) randomised,
double-blind, placebo-controlled trial.
Hans-Christoph Diener et. al., Lancet. 2004 Jul
24-30364(9431)331-7
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Methods

• Design Randomized double blind placebo
  controlled trial
• Method of randomization Computer generated list
  of treatment numbers
• Unit of randomization Person
• Method of allocation concealment Central
  treatment allocation
• Number randomized 7599
• Exclusions post randomization None
• Number analyzed ASA Clopidogrel 3797,
  Placebo Clopidogrel 3802 by Intention to
  treat
• Masking Double-blind
• Losses to follow up Figure 1 Almost identical
  in both groups, Data available on 96 of patients
  at 18 months

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Participants

• Country 28 countries, 507 centers
• Age gt40 yrs
• Gender 63 Male
• Inclusion Criteria Ischemic Stroke / TIA in
  previous 3 months one of five risk factors
• Exclusion Criteria Severe co-morbid conditions,
  increased risk of bleeding, PUD,
  Contraindications for ASA or Clopidogrel

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Interventions

• Treatment ASA 75 mg Clopidogrel 75 mg
• Control Clopidogrel 75 mg Placebo
• Follow up 18 months
• Follow up visits 1, 3, 6, 12, 18 months, Monthly
  telephone calls

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Outcomes

• Primary Outcome Composite of ischemic stroke,
  MI, Vascular death, rehospitalization for acute
  ischemic event
• Secondary Outcomes Individual and combination of
  each of those forming composite endpoint, Death,
  Any stroke
• Outcome assessment at ? follow up visits, monthly
  phone calls, exact method not reported

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Notes

• Study Period 2000- 2003
• Control group event rate 16.7
• Equivalence of baseline characteristics Table 1
• Subgroup analysis Fig. 3/ Table 3 Prespecified
• Adverse events Monitored and Reported
• Quality of life indicators Not studied
• Funding Sanofi-Synthelabo Research and Bristol
  Myers-Squibb

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Statistical Analysis

• Power calculation based on CAPRIE
• ITT analysis
• First occurrence of event, censoring
• Assessment of potential confounders
• Hypothesis testing based on 2 sided p of 5
• Survival curves compared with Log rank test
• Cox-Proportional Hazards models to calculate RR
• Additional On-Treatment analysis ITT
• Safety/ Adverse events monitored by Steering
  committee/ Data safety monitoring board

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What are the results
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Results

• Primary Outcome
• Table 2, Figure 2
• Secondary Outcomes
• Table 3
• Subgroup analysis
• Figure 3
• Adverse events
• Table 4

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Critical Appraisal
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Are the results valid
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Are they important
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Results Second Look

• Primary Outcome
• ARR 1.0 (-0.6-2.7)
• RRR 6.4 (-4.6-16.3)
• Statistically appropriate, however
• RR 0.94 (0.85-1.04)
• Approx NNT 96 (37- NNH)
• Not as attractive as ARR and RRR
• Similar for Secondary outcomes
• Sub groups Claim of slight favor for combination
  not consistent with data presented
• Adverse events
• ARR (I) 1.26 (0.64-1.88)
• What about RR/RRI as in other tables?
• RR 1.92 (1.37 -2.7) 92 Increase risk of
  fatal bleed
• NNH 80 (56-164)
• Not as attractive as ARR

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Will the results help me in caring for my
patient
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Clinical Question Is the combination of
Clopidogrel and Aspirin superior to Aspirin alone
in reducing Mortality or in decreasing risk of
Stroke in a 65 yr old obese gentleman s/p
Ischemic stroke and with HTN and Metabolic
syndromeAnswerWhat do you think?What about
ASA ER DipyridamoleWhat about the concern for
ACS with ER Dipyridamole
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• Thank You