MATCH

Aspirin 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 (2004)

Managment of ATherothrombosis with Clopidogrel in High-risk patients

Design: Randomised, double-blind, placebo-controlled trial (Dec 2000 – April 2002)

  • 507 centres (stroke units and neurology departments) in 28 countries
P  N = 7599
High risk patients with recent ischemic stroke or TIA and at least one additional vascular risk factor who were already receiving clopidogrel 75mg dailyInclusion:

  • ischemic stroke or transient ischemic attack in the previous 3 months
    • categorised ischemic stroke with the TOAST classification
  • 1 or more of 5 additional risk factors – previous ischemic stroke, previous myocardial infarction, angina pectoris, diabetes mellitus or symptomatic peripheral arterial disease within the previous 3 years

Exclusion:

  • age < 40 yo
  • severe comorbid conditions
  • increased risk of bleeding (clinical evience of severe hepatic insufficiency, current peptic ulceration, history of systemic bleeding or other history of bleeding diathesis or coagulopathy)
  • scheduled for major surgery or vascular surgery
  • contraindications for aspirin or clopidogrel

Patient characteristics – fairly well balanced between treatment arms

  • Mean age ~ 66 yo
  • 37% female
  • Qualifying event – 21% TIA, 79% ischemic stroke
    • TOAST classification:
      • 34% large artery atherosclerosis
      • 53% small vessel occlusion
      • 2-3% cardioembolism
  • 50% 7 days to 1 month from qualifying event
  • 74% none to slight disability (Modified Rankin scale)
  • 26% ischemic stroke history
  • 19% tia history
  • 5% MI history
  • 78% hypertension
  • 68% diabetes
  • 57% hypercholestermia
  • 48% past or current smoker
  • 80% on aspirin at baseline
I Aspirin 75mg daily (+ Clopidogrel 75mg daily)
Duration of treatment + f/u: 18 months
C Placebo daily (+ Clopidogrel 75mg daily)
Duration of treatment + f/u: 18 months
O Primary endpoint: composite of ischemic stroke, myocardial infarction, vascular death (including haemorrhagic death of any origin) or rehospitalization for acute ischemia (including rehospitalization for TIA, angina pectoris or worsening of peripheral arterial disease requiring therapeutic iintervention or urgent revascularization or transient ischemic attack)

Secondary endpoints:

  • individual and various combinations of the primary endpoint
  • any death
  • any stroke

Safety:

  • incidence of life-threatening bleeding (any fatal bleeding event, a drop in hgb of >50g/L, significant hypotension with need for inotropes (haemorrhagic shock), symptomatic intracranial haemorrhage or transfusion of >4 units of RBC or equivalent amount of whole blood) and major bleeding (defined as significant disabling (with persistent sequalae)), intra-ocular bleeding leading to significant loss of vision or transfusion of <3 units of RBC or equivalent amount of whole blood

Analysis: Intention to treat (irrespective of compliance to protocol)
Power: 80% power, N = 7600 – to detect a 14% relative risk reduction
Funding: Sanofi Synthelabo – undertake site monitoring and data management, and provide input into the study by putting employee into the steering committee

Results:

Efficacy:

  • Primary composite endpoint:
    • RRR: 9.5% (CI: -2 to 19.6%)
  • All stroke NSS
  • Ischemic stroke NSS
  • All-cause mortality NSS

Safety:

  • Life-threatening bleeding:
    • ARR: 1.26% (0.64-1.88) p < 0.0001
    • No early increase in life-threatening bleeding and primary intracranial haemorrhage)
    • No report of haemorrhagic transformations of ischemic stroke
  • GI bleeds
    • Life-threatening: 1.4% vs. 0.6%
    • Major: 1.12% vs 0.29%
  • Fatal bleeds: NSS
  • Symptomatic intracranial haemorrhage:
    • ARR: 0.40% (0.04-0.76)
  • Minor bleeding:
    • ARR: 2.16% (1.51-2.81) p < 0.0001
  • symptomatic intracranial haemorrhage was  more frequent in the aspirin group than in patients allocated placebo; however, in both treatment arms, no haemorrhageic transformations of ischemic stroke were reported as life-threatening bleeding (1.4% vs. 0.6% and 1.12% vs. 0.29%

Take-home points:

  • Aspirin ADDED to clopidogrel (not clopidogrel ADDED to aspirin) resulted in signigifantly higher bleeding with no significant efficacy benefit
  • Patient population are “select high-risk patients”