Management of Atherothrombosis With Clopidogrel in High-Risk Patients - MATCH

Description:

The goal of the MATCH trial was to evaluate aspirin plus clopidogrel compared with clopidogrel alone for the prevention of vascular events and the risk of bleeding in high-risk patients with recent ischemic stroke or transient ischemic attack (TIA) and at least one additional vascular risk factor.

Study Design

Study Design:

Patients Enrolled: 7,599
Mean Follow Up: 18 months
Mean Patient Age: Mean age 66 years
Female: 37

Patient Populations:

Ischemic stroke or TIA in previous three months and had ≥1 of the following risk factors within the previous three years: previous ischemic stroke, previous MI, angina pectoris, diabetes, or symptomatic peripheral arterial disease

Exclusions:

Age <40 years, severe comorbid conditions, increased risk of bleeding, scheduled for major surgery or vascular surgery, and contraindications for aspirin or clopidogrel

Primary Endpoints:

Composite of ischemic stroke, MI, vascular death, or rehospitalization for an acute ischemic event

Secondary Endpoints:

Individual and various combinations of each of the components of the primary endpoint; any death; and any stroke

Drug/Procedures Used:

Patients who were already receiving clopidogrel (75 mg/day) were randomized to treatment with aspirin (75 mg/day) (n=3,797) or placebo (n=3,802).

Principal Findings:

Mean time from index event to randomization was 26.5 days. The majority of patients in the trial had an ischemic stroke as the qualifying event (79%), while the remaining 21% had a TIA. Per the inclusion criteria, 79% had one additional risk factor and 20% had two additional risk factors.

There was no difference in the primary composite endpoint of ischemic stroke, myocardial infarction (MI), vascular death, or rehospitalization for an acute ischemic event (16% in aspirin plus clopidogrel group vs. 17% in clopidogrel alone group, relative risk reduction 6.4%, 95% confidence interval -4.6% to 16.3%, p=0.244). There was also no difference in any of the secondary endpoints, including MI (2% each, p=0.660), ischemic stroke (8% vs. 9%, p=0.353), all-cause mortality (5% each, p=0.992), or any stroke (9% each, p=0.790).

Bleeding events were significantly higher in the aspirin plus clopidogrel group compared with the clopidogrel alone group, including life-threatening bleeding (3% vs. 1%, p<0.0001), major bleeding (2% vs. 1%, p<0.0001), and minor bleeding (3% vs. 1%, p<0.0001). There was no difference in fatal bleeding, although the number of events was small (n=16 vs. n=11).

Interpretation:

Among high-risk patients with recent ischemic stroke or TIA and at least one additional vascular risk factor, treatment with aspirin plus clopidogrel was not associated with a difference in the primary composite endpoint or any of the secondary endpoints at 18-month follow-up compared with clopidogrel alone, with an additional increase in bleeding in the aspirin plus clopidogrel group.

These findings are unlike those of the CURE and CREDO trials, which showed benefit with aspirin and clopidogrel with minimal increases in bleeding in patients with a coronary event. However, the comparison group in those trials was aspirin alone rather than clopidogrel alone. Additionally, the lack of benefit is in line with the subgroup analysis of the CAPRIE trial of patients with an ischemic stroke as a qualifying event, which showed no significant benefit of clopidogrel over aspirin.

References:

Diener HC, Bogousslavsky J, Brass LM, et al. 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. Lancet 2004;364:331-7.

Clinical Topics: Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Statins

Keywords: Stroke, Myocardial Infarction, Ischemic Attack, Transient, Follow-Up Studies, Platelet Aggregation Inhibitors, Peripheral Arterial Disease, Ticlopidine, Risk Factors, Purinergic P2Y Receptor Antagonists, Confidence Intervals, Diabetes Mellitus, Dipyridamole


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