MATCH (Management of ATherothrombosis with Clopidogrel in High-risk patients) trial

• in the CAPRIE trial Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease and its benefit was amplified in some high-risk subgroups of patients
  • In the CAPRIE trial, clopidogrel was superior to aspirin in the overall population of patients with recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease, reducing the relative risk for the primary endpoint (ischaemic stroke, myocardial infarction, or vascular death) by 8·7% versus aspirin (p=0·043). For the subgroup of patients with ischaemic stroke as the qualifying event the relative risk reduction was 7·3% and not significant. However, the CAPRIE study was not designed to specifically address this subgroup of patients
• The MATCH (Management of ATherothrombosis with Clopidogrel in High-risk patients) trial aimed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk
  • MATCH aimed to find out whether aspirin added to clopidogrel would further reduce the risk of recurrent ischaemic vascular events in high-risk patients after transient ischaemic attack or ischaemic stroke
• Trial design
  • this was a randomised, double-blind, placebo-controlled trial to compare aspirin (75 mg/day) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day. Duration of treatment and follow-up was 18 months. The primary endpoint was a composite of ischaemic stroke, myocardial infarction, vascular death, or rehospitalisation for acute ischaemia (including rehospitalisation for transient ischaemic attack, angina pectoris, or worsening of peripheral arterial disease). Analysis was by intention to treat, using logrank test and a Cox's proportional-hazards model
• Study results
  • this study revealed that 596 (15.7%) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 (16·7%) in the clopidogrel alone group (relative risk reduction 6.4%, [95% CI –4·6 to 16·3]; absolute risk reduction 1% [–0·6 to 2·7])
  • life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone (96 [2·6%] vs 49 [1·3%]; absolute risk increase 1·3% [95% CI 0·6 to 1·9]).
  • major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality
• Study conclusions:
  • the study authors concluded that adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events
  • it was noted that the risk of life-threatening or major bleeding is increased by the addition of aspirin and the authors concluded that " ...because of benefit to risk considerations, the trial did not show additional clinical value of adding aspirin to clopidogrel in high-risk patients with transient ischaemic attack or ischaemic stroke (1)."

Reference:

1. Lancet. 2004 Jul 24;364(9431):331-7.