Secondary prevention after cerebral ischaemia of presumed arterial origin: is aspirin still the touchstone?

Patients who have had a transient ischaemic attack or nondisabling ischaemic stroke of presumed arterial origin have an annual risk of death from all vascular causes, non-fatal stroke, or non-fatal myocardial infarction that ranges between 4% and 11% without treatment. 2 In the secondary prevention of these vascular complications the use of aspirin has been the standard treatment for the past two decades. Discussions about the dose of aspirin have dominated the issue for some time, although there is no convincing evidence for any diVerence in eVectiveness in the dose range of 30-1300 mg/day. 3 A far greater problem is the limited degree of protection oVered by aspirin: the accumulative evidence from trials with aspirin alone and only for cerebrovascular disease of presumed arterial origin as qualifying event indicates that a dose of aspirin of at least 30 mg/day prevents only 13% of serious vascular complications. 2 In this commentary we use the AntiPlatelet Trialists’ (APT) composite outcome event—death from all vascular causes, non-fatal stroke, or non-fatal myocardial infarction—unless otherwise stated. An outcome event that takes the entire vascular burden into account is most relevant from the perspective of a patient. In other words 87% of the major arterial complications are not avoided with aspirin. The question therefore is: Do we have something “stronger”? Until recently the only alternative drug was ticlopidine. A direct comparison with aspirin was made in the Ticlopidine Aspirin Stroke Study (TASS). A total of 3069 patients with transient or non-disabling cerebral ischaemia were randomised between ticlopidine (250 mg twice daily) or aspirin (650 mg twice daily). The occurrence of non-fatal myocardial infarction was not reported in the original document, but data on the APT composite event were reported later. The relative risk reduction (RRR) was a 6% advantage in favour of ticlopidine, but the 95% confidence interval (95%CI) was compatible with no diVerence at all (−7 to 17%). Thus ticlopidine is about as eVective as aspirin. A major disadvantage is, however, that it is definitely more toxic. Diarrhoea and skin rashes were reported in up to 20 and 14%, respectively, and neutropenia in about 1%. In the past 2 years three trials in patients with cerebral ischaemia of presumed arterial origin also tried to find a more eYcacious treatment than aspirin, in diVerent ways.