CAST - RANDOMIZED PLACEBO-CONTROLLED TRIAL OF EARLY ASPIRIN USE IN 20000 PATIENTS WITH ACUTE ISCHEMIC STROKE

Background Aspirin is effective in the treatment of acute myocardial i nfarction and in the long-term prevention of serious vascular events i n survivors of stroke and myocardial infarction. There is, however, no reliable evidence on the effectiveness of early aspirin use in acute ischaemic stroke. Methods The Chinese Acute Stroke Trial (CAST) was a large randomised, placebo-controlled trial of the effects in hospital of aspirin treatment (160 mg/day) started within 48 h of the onset of suspected acute ischaemic stroke and continued in hospital for up to 4 weeks. The primary endpoints were death from any cause during the 4-w eek treatment period and death or dependence at discharge, and the ana lyses were by intention to treat. 21 106 patients with acute ischaemic stroke were enrolled in 413 Chinese hospitals at a mean of 25 h after the onset of symptoms (10 554 aspirin, 10 552 placebo). 87% had a CT scan before randomisation. It was prospectively planned that the resul ts would be analysed in parallel with those of the concurrent Internat ional Stroke Trial (IST) of 20 000 patients with acute stroke from oth er countries. Findings There was a significant 14% (SD 7) proportional reduction in mortality during the scheduled treatment period (343 [3. 3%] deaths among aspirin-allocated patients vs 398 [3.9%] deaths among placebo-allocated patients; 2p=0.04). There were significantly fewer recurrent ischaemic strokes in the aspirin-allocated than in the place bo-allocated group (167 [1.6%] vs 215 [2.1%]; 2p=0.01) but slightly mo re haemorrhagic strokes (115 [1.1%] vs 93 [0.9%]; 2p>0.1). For the com bined in-hospital endpoint of death or non-fatal stroke at 4 weeks, th ere was a 12% (6) proportional risk reduction with aspirin (545 [5.3%] vs 614 [5.9%]; 2p=0.03), an absolute difference of 6.8 (3.2) fewer ca ses per 1000. At discharge, 3153 (30.5%) aspirin-allocated patients an d 3266 (31.6%) placebo-allocated patients were dead or dependent, corr esponding to 11.4 (6.4) fewer per 1000 in favour of aspirin (2p=0.08). Interpretation There are two major trials of aspirin in acute ischaem ic stroke. Taken together, CAST and the similarly large IST show relia bly that aspirin started early in hospital produces a small but defini te net benefit, with about 9 (SD 3) fewer deaths or non-fatal strokes per 1000 in the first few weeks (2p=0.001), and with 13 (5) fewer dead or dependent per 1000 after some weeks or months of followup (2p<0.01 ).