IST AND CAST : SOME ANSWERS BUT MORE QUESTIONS

Stroke is the third most common cause of death in come was looked at as a major end-point. In the IST 6-month outcome figures (Figure 1), there were only the West and the commonest cause of adult disability. Unfortunately, efficacious treatments have 1.3% more people independent in the aspirin group compared with the non-aspirin group. Contrasts can remained elusive until recently. A natural starting point for developing treatments for acute ischaemic be made here with the NINDS rt-PA study where thrombolysis was shown to be associated with a 11– stroke has been to assess successful therapies for another vascular condition, myocardial infarction, 13% improvement in the best clinical outcome with a similar non-significant improvement in mortality. in particular aspirin, heparin and thrombolysis. The question whether aspirin is first, beneficial So it would seem that rt-PA is undeniably more effective. However, in favour of aspirin is the fact and second, safe in the acute stages of stroke has been addressed in two recent megatrials: the Interthat only a small proportion (,10%) of patients presenting with ischaemic stroke would satisfy crinational Stroke Trial (IST) and the Chinese Acute Stroke Trial (CAST). The IST also looked at two teria for the use of thrombolysis, compared with aspirin which could be given to most (.90%). doses of subcutaneous unfractionated heparin; a ‘venous’ dose of 5000 IU b.d. and an ‘arterial’ dose At first glance it would seem that heparin would have no role in the acute treatment of stroke. In the of 12 500 IU b.d. Both trials had around 20 000 patients. IST had a 2×3 factorial design and although IST primary outcome measures (Table 1), the small acute mortality benefit was not reflected at 6 months randomised was not placebo-controlled or blind. CAST was a placebo-controlled and double-blind trial of aspirin alone. Table 1 Summary of the main trial outcomes, % events prevented. (All the data is combined in one table bearing in mind The aspirin results from the two trials were very differences in treatment period and specified outcomes in IST similar (Table 1). When taking the primary outcome and CAST) measures, early death, and later death or dependency, there is a trend toward mortality reduction IST CAST in the acute stages (just statistically significant in CAST), and a small benefit is also seen in the later Asp vs No Hep vs No Asp vs No end-points. However, it is only by combining the trials and the early end-point with early recurrent Primary outcomes non-fatal stroke that a reasonably convincing statDeath early 0.4 0.3 0.54 istical result is obtained. By doing this an absolute 2 weeks (IST) NS NS 2P = 0.04 reduction (AR) in early death and non-fatal stroke 4 weeks (CAST) by 0.9% (2P = 0.001) and late death and dependency Death/Dependence 1.3 0 1.14 by 1.3% (2P = 0.01) is seen. By far the most striking 6 months (IST) NS NS NS result to come from these trials is the reduction in Discharge (CAST) early recurrent ischaemic stroke with aspirin, and Secondary outcomes presumably a large part of the later mortality and dependency benefit was due to this. The acute use Recurrent Ischaemic 1.1 0.9 0.47 Stroke 2P , 0.001 2P , 0.01 2P = 0.01 of aspirin can be recommended on this basis, more so than for the acute treatment of the initial cereHaemorrhagic −0.1 −0.8 −0.21 bral infarction. Stroke NS 2P , 0.00001 NS This conclusion would also apply if a good outAll 0.9 0.2 0.16 2P , 0.001 NS NS