doi: 10.1161/01.STR.0000157951.72934.0b
(Stroke. 2005;36:707.)
© 2005 American Heart Association, Inc.
Letters to the Editor |
Emerging Therapies: Clopidogrel and Aspirin
NJ Neuroscience Institute at JFK Medical Center, Seton Hall University, Edison, NJ
To the Editor:
We read with interest the commentaries regarding the recently published Management of Atherothrombosis with Clopidogrel in High-Risk Patients (MATCH) trial1 and wish to contribute some additional perspectives. Patient baseline characteristics have been cited as reasons for the neutral results and detrimental outcomes observed.1
The large number of patients with small-vessel qualifying events is one reason cited for treatment failure, and Dr Caplan notes that there were "too few patients with documented large-artery disease in MATCH." On the contrary, the prevalence of lacunar infarctions among participants in MATCH was similar to or less than that of other recent large randomized cerebrovascular trials (53% versus 56% to 67%),2–4 whereas the proportion of patients with large-vessel infarctions was greater (34% versus 12% to 20%).2–4 Additionally, as Dr Caplan himself states, some patients with large-artery disease may have been misdiagnosed as "lacunar" if adequate intracranial artery studies were not performed. Given the preponderance of diabetes in the MATCH study population, intracranial atherosclerosis may well have been underestimated, and thus the total percentage of large-vessel qualifying infarctions may have exceeded the reported 34%.2 Notably, outcome analyses were negative for lacunar and large-vessel subgroups.2
The frequency of hypertension was also greater than that of most previous studies (78% versus 51% to 68%)2,3,5,6 but less than that of a recent trial evaluating ticlopidine against aspirin in black patients (86%).4 In contrast to MATCH, no increase in intracranial hemorrhages was observed in the ticlopidine study.4 There was also no increase in intracranial hemorrhages in the 2 trials that had comparable or greater frequencies of lacunar infarctions as qualifying events (53% versus 56% to 67%).3,4 Drs Amarenco and Donnan argue that the greater rate of severe hemorrhages from clopidogrel/aspirin may have been attributable to the low risk incurred from clopidogrel alone because clopidogrel has been found to cause fewer (mostly gastrointestinal) hemorrhages when compared with aspirin.6 However, the rate of intracranial hemorrhage has not been shown to be significantly different between aspirin and clopidogrel,6 and thus the increase in intracranial hemorrhages in MATCH must be considered cautiously. Further, the severe systemic hemorrhagic complications in MATCH recapitulate the adverse events seen in previous cardiovascular thienopyridine–aspirin combination trials.7,8
In MATCH, the prevalence of diabetes exceeded that of any previous cerebrovascular study (68% versus 15% to 40%),2–6 and as Drs Amarenco and Donnan point out meta-analyses of antiplatelet agents have demonstrated reduced efficacy in diabetic patients with vascular disease.9 However, the data referred to did not specifically pertain to patients with cerebrovascular disease, and in fact patients with carotid disease were grouped separately in that analysis.9 Information regarding the effectiveness of antiplatelet agents in cerebrovascular patients with diabetes is lacking, but to date there is little evidence for diminished efficacy.
Finally, Drs Amarenco and Donnan mention that many patients included in MATCH had experienced recurrent infarctions while on aspirin, and that the MATCH patients did not represent the population for whom many neurologists prescribe aspirin plus clopidogrel. Our experience has been the opposite, in that it is exactly these patients for whom combination treatment with aspirin/clopidogrel is so often prescribed inappropriately.
References
1. Fisher M, Davalos A. Emerging therapies: MATCH and other trials. Stroke. 2004; 35: 2604–2609.
2. Diener H, Bogousslavsky J, Brass L, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht H. Aspirin and clopidogrel compared with clopidogrel alone after recent ischemic stroke or transient ischemic attack in high-risk patients (MATCH): a randomized double-blind placebo-controlled trial. Lancet. 2004; 364: 331–337.[CrossRef][Medline] [Order article via Infotrieve]
3. Mohr J, Thompson J, Lazar R, Levin B, Sacco R, Furie K, Kistler J, Albers G, Pettigrew L, Adams H, Jackson C, Pullicino P. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001; 345: 1444–1451.
4. Gorelick P, Richardson D, Kelly M, Ruland S, Hung E, Harris Y, Kittner S, Leurgans S. Aspirin and ticlopidine for prevention of recurrent stroke in black patients. J Am Med Assoc. 2003; 289: 2947–2957.
5. Diener H, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. ESPS 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996; 143: 1–13.[CrossRef][Medline] [Order article via Infotrieve]
6. CAPRIE Steering Committee. A randomized blinded trial of Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE). Lancet. 1996; 348: 1329–1339.[CrossRef][Medline] [Order article via Infotrieve]
7. The CURE Trial Investigators. Effects of Clopidogrel in Addition to Aspirin in Patients With Acute Coronary Syndromes Without ST-Segment Elevation. N Engl J Med. 2001; 345: 494–502.
8. Steinhubl S, Berger P, Mann J, Fry E, DeLago A, Wilmer C, Topol E. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. J Am Med Assoc. 2002; 288: 2411–2420.
9. Antithrombotic Trialists’ Collaboration. Collaborative Meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients. BMJ. 2002; 324: 71–86.
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