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Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke (MATCH)
Aim
The aim of the MATCH trial was 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. It 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).
References:
Diener et al. Cerebrovasc Dis. 2004;17(2-3):253-61.
Diener et al. Lancet 2004; 364: 331-337.
Study Objectives and Design
The MATCH trial was designed to determine:
- The efficacy and safety of ASA compared to placebo in high-risk cerebrovascular patients receiving clopidogrel 75mg
References:
Diener HC. WSC Vancouver. June 2004.
Findings – Primary Endpoint
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]).
Primary Endpoint (ITT)
No significant RRR of clopidogrel + ASA compared to clopidogrel alone
Findings – Bleeding risk
Addition of aspirin to clopidogrel in the MATCH trial resulted in a significantly higher bleeding rate that offset any beneficial effect. 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.
The bleeding complications in MATCH were constant over time, which could indicate that for long-term trials, a time margin exists at which risk outweighs benefit.
Number (%) of Patients With Bleeding Events
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Number (%) with event |
Difference (%) between aspirin and placebo (95% Cl) |
P* |
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Aspirin and clopidogrel (n=3759) |
Placebo and clopidogrel (n=3781) |
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Life-threatening bleeding |
96 (3%) |
49 (1%) |
1-26
(0-64 to 1-88) |
<0.0001 |
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Fatal bleeding |
16 (<1%) |
11 (<1%) |
0.13 (–0.14 to 0.40) |
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Non-fatal
bleeding |
81 (2%) |
38 (1%) |
1.15 (0.59 to 1.71) |
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Symptomatic intracranial Haemorrhage |
40 (1%) |
25 (1%) |
0.40 (–0.01 to 0.82) |
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Primary intracranial Haemorrhage |
32 (1%) |
17 (<1%) |
0.40 (0.04 to 0.76) |
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Major bleeding |
73 (2%) |
22 (1%) |
1.36
(0.86 to 1.86) |
<0.0001 |
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Minor bleeding |
120 (3%) |
39 (1%) |
2.16
(1.51 to 2.81) |
<0.0001 |
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* Person's chi² test. All symptomatic (and thus primary) intracranial haemorrhages were life-threatening bleeds.
Bleeding Complications Increased Significantly
Take home message
What are the practical outcomes of the MATCH?
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. However, the risk of life-threatening or major bleeding is increased more than double by the addition of aspirin.
References:
Diener et al. Lancet 2004; 364: 331-337.
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© 2005 Boehringer Ingelheim GmbH, Germany. All rights reserved.
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