Aspirin Therapy Should Be First Line:
Probably, But Watch This Space
Our protagonists deal with a thorny problem: what should be first-line therapy in the secondary prevention of stroke? They both agree on the evidence: aspirin works, clopidogrel works slightly better than aspirin when a multiple vascular outcome cluster is considered, and dipyridamole seems to have an additive effect to that of aspirin alone for stroke prevention. Warlow points out that the additive benefits of dipyridamole plus aspirin are based on a single trial (ESPS2) and that the mechanism of this effect is unclear.
Our practice is to use aspirin alone as first-line therapy but to substitute either clopidogrel (broad-spectrum vascular protection) or add dipyridamole (additive benefits for stroke protection) if a second clinical event has occurred. In aspirin-intolerant patients, we would use clopidogrel. These strategies seem to be generally accepted. However, Diener and other clinicians advocate aspirin plus dipyridamole as first-line therapy for secondary stroke prevention. There is no consensus on this issue, and practice may vary from country to country depending on licensing arrangements. Given the modest benefits of clopidogrel over aspirin in CAPRIE and the encouraging results of the CURE trial in patients with myocardial ischemia, we agree with both contributors that the combination of aspirin plus clopidogrel is potentially more attractive than clopidogrel alone.
Clearly, more evidence is required. We await with interest the results of the MATCH trial, comparing aspirin plus clopidogrel with clopidogrel alone. Warlow suggests the “dream trial” that would compare aspirin alone, aspirin plus clopidogrel, and aspirin plus dipyridamole in a 3-arm design. Interestingly, a 2-arm comparison of these combination therapies is being planned. We also await the results of ESPRIT, which will provide further information about the efficacy of aspirin versus aspirin plus dipyridamol.
While further data will clarify matters, we should not forget that protection against vascular events is still only modest, at approximately 20%. With 80% to go, better strategies are clearly needed. Fortunately, there are a number of newer-generation antiplatelet and antithrombotic agents in the pipeline, some of which are already in phase III trial.
The opinions expressed in this editorial are not necessarily those of the editors or of the American Stroke Association.