Clopidogrel and Aspirin: New Data From COMMIT
Abstract & Commentary
By John J. Caronna, MD, Vice-Chairman, Department of Neurology, Cornell University Medical Center, Professor of Clinical Neurology, NewYork Presbyterian Hospital. Dr. Caronna reports no consultant, stockholder, speaker's bureau, research, or other relationship related to this field of study.
Synopsis: In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events in hospital, and should be considered routinely.
Source: Chen ZM, et al. COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group. Addition of Clopidogrel to Aspirin in 45,852 Patients With Acute Myocardial Infarction: Randomized Placebo-Controlled Trial. Lancet. 2005;366:1607-1621.
In 2004, the match trial1 results indicated that in patients with recent ischemic stroke or transient ischemic attack (TIA), the addition of aspirin (ASA) 75mg. daily to clopidogrel 75mg. daily did not reduce the risk of recurrent cerebral ischemic events, but did increase the risk of major bleeding compared with clopidogrel alone. Therefore, many neurologists discontinued the use of clopidogrel in combination with ASA in favor of the use of ASA alone or in combination with extended release dipyridamole.
In COMMIT, 46,000 patients with suspected acute myocardial infarction (MI) at 120 hospitals in China, were randomly allocated to ASA 162mg. daily and clopidogrel 75mg. daily without a loading dose, or to ASA and placebo. Treatment continued until hospital discharge or until day 28, whichever came sooner (mean 15 days in survivors). At the end of treatment, a form was completed concerning compliance with study treatment, use of other therapies, possible side effects of study medication, and major clinical events.
Allocation to ASA plus clopidogrel produced a significant (9%) relative reduction in death, recurrent MI, or stroke compared to ASA alone. There also was a significant (7%) relative reduction in death. These effects on death, recurrent MI, or stroke were consistent across a wide range of patients, and were independent of other treatments being used.
There was no excess risk of fatal, transfused, or cerebral bleeds in the clopidogrel group, either overall or in patients older than 70 years of age, or in those treated with fibrinolytic drugs.
Commentary
The contradictory findings of the COMMIT and MATCH trials are not strictly comparable. COMMIT studied the acute effects of clopidogrel added to ASA in patients admitted within 24 hours of a suspected acute MI. During the critical period of one day to 4 weeks after MI, combination antiplatelet therapy produced a clinical benefit without excess major bleeding or intracranial hemorrhage.
In contrast, MATCH randomized patients several weeks (mean, 26.5 days) after the acute phase of ischemic stroke or TIA. MATCH studied the addition of ASA to clopidogrel treatment and follow-up continued for more than a year. At 18 months, compared with clopidogrel alone, the risk of major bleeding with the addition of ASA outweighed any benefit.
The results of COMMIT indicate only that combination antiplatelet therapy with ASA and clopidogrel has benefit in the critical care setting of acute MI, without an excess risk of serious bleeding complications. The clinical benefit of clopidogrel emerged as early as the first day, even though no loading dose was given in this study. There was no excess risk of serious bleeding complications in this group of hospitalized patients without symptomatic cerebrovascular disease at entry in the study.
For the neurologist, the results of COMMIT suggest that combination therapy might be useful in the acute stroke setting, and that a similar mega trial should be undertaken to study the question.
References
1. Diener HC, 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;364:331-337.
In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events ...You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content