Fast track — ArticlesAspirin 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
Introduction
Antiplatelet therapy is a proven component of secondary prevention in patients with transient ischaemic attack or ischaemic stroke.1 In the CAPRIE trial,2 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. In post-hoc analyses, the benefit of clopidogrel was shown to be amplified in high-risk subgroups, including patients with a history of previous ischaemic stroke or myocardial infarction,3 those with diabetes,4 those with previous cardiac surgery,5 and those receiving lipid-lowering therapy.6 In patients with a history of previous ischaemic stroke or myocardial infarction before their qualifying event, clopidogrel produced a relative risk reduction of 14·9% versus aspirin for the primary CAPRIE endpoint.
Findings of randomised controlled trials in patients with coronary manifestations of atherothrombosis (CURE, CREDO)7, 8 have shown the sustained benefit of clopidogrel on top of standard treatment including aspirin. These therapeutic benefits were all obtained with an acceptable increase in the risk of major bleeding complications.7, 8 These trials provided the rationale to undertake MATCH (Management of ATherothrombosis with Clopidogrel in High-risk patients), 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. The potential bleeding risk after addition of aspirin to clopidogrel in some stroke populations, such as in small-vessel disease (patients with lacunar stroke), could not be estimated from previous cardiology trials. Here, we report the main findings from the MATCH trial.
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Patients
Between December, 2000, and April, 2002, we enrolled individuals at 507 centres (stroke units and neurology departments) in 28 countries. Patients were eligible for inclusion in the study if they had had an ischaemic stroke or transient ischaemic attack in the previous 3 months and had one or more of five additional risk factors—previous ischaemic stroke, previous myocardial infarction, angina pectoris, diabetes mellitus, or symptomatic peripheral arterial disease—within the previous 3 years.
Results
A total of 7599 patients were randomised: 3802 were allocated placebo and clopidogrel and 3797 aspirin and clopidogrel (figure 1). At 18 months of follow-up, data were available for 7276 patients (96%), including those who died during the study and those alive at the end of the 18-month period of follow-up: 3621 in the aspirin and clopidogrel group and 3655 in the placebo and clopidogrel group. In 13 patients, vital status was not obtained.
Table 1 shows baseline demographics and medical
Discussion
In most patients, a consistent reduction of primary and secondary vascular events was recorded with aspirin added to clopidogrel, although the differences were not significant. The relative risk reduction in favour of aspirin in the intention-to-treat population of 6·4% is in the range that was reported in the CAPRIE trial (8·7%).2 Addition of aspirin to clopidogrel in the MATCH trial resulted in a significantly higher bleeding rate that offset any beneficial effect. No significant increase in
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