40, 95% CI 0.17 to 0.97, p=0.041), and composite of MACE and all-cause mortality (adjusted HR=0.66, 95% CI 0.55 to 0.78, p<0.001). The risk of all-cause mortality
was not different between clopidogrel and aspirin users (adjusted HR=0.97, 95% CI 0.73 to 1.30, p=0.853; table 2). The benefit of clopidogrel was consistent across eight subgroups of baseline characteristics in stratified analysis for future selleck catalog MACE (figure 2). Table 2 Occurrence of primary and secondary end points and unadjusted and adjusted HRs by clopidogrel vs aspirin Figure 1 Kaplan-Meier curves for major adverse cardiovascular events among clopidogrel and aspirin groups. Figure 2 Stratified analysis for future adjusted risks of major adverse cardiovascular events according to baseline characteristics (clopidogrel vs aspirin). Discussion The ‘breakthrough’ ischaemic cerebrovascular event in a patient on aspirin is a common scenario frequently encountered by clinicians caring for patients with stroke. Strategies for instituting an antithrombotic regimen to prevent future vascular events in such patients vary widely, largely because there is no dedicated clinical trial evidence to guide practitioners. Few patient registries have the scale, relevant antiplatelet information, or long term follow-up assessment capacity to provide insights into this issue. On the basis of the
Taiwan NHIRD, we found, in the event of stroke while on aspirin, switching to clopidogrel is associated with fewer vascular events and fewer recurrent strokes. While these observational data can only be seen as suggestive, the current results may provide clinicians modest evidence-based guidance while they wait for additional data from randomised controlled trials of antithrombotic regimens vs aspirin reinitiation among aspirin treatment failures. Currently, clopidogrel, aspirin and aspirin plus extended-release dipyridamole are recommended as initial first-line options in preventing recurrent stroke.8 Indeed, clinical trials suggest that aspirin plus extended-release dipyridamole has superior efficacy to aspirin monotherapy,14 and clopidogrel
appears to have similar effects on secondary stroke prevention when compared to aspirin plus extended-release dipyridamole.15 While there have been no dedicated head to head Batimastat trials of clopidogrel vs aspirin among patients with ischaemic stroke, based on the aforementioned clinical trial data, one could indirectly infer that clopidogrel may be better than aspirin for secondary stroke prevention in patients with ischaemic stroke overall. Also, greatest platelet inhibitory effect of clopidogrel is found in people with the least inhibition of platelet aggregation by aspirin.16 As such it is conceivable that clopidogrel may confer the greatest benefit for patients with aspirin treatment failure. We found patients receiving aspirin, as compared to clopidogrel, tended to take another antiplatelet agent together and had higher risk of intracranial haemorrhage.