Elsevier

The Lancet

Volume 349, Issue 9066, 7 June 1997, Pages 1641-1649
The Lancet

Articles
CAST: randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke*

https://doi.org/10.1016/S0140-6736(97)04010-5Get rights and content

Summary

Background

Aspirin is effective in the treatment of acute myocardial infarction and in the long-term prevention of serious vascular events in 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-week treatment period and death or dependence at discharge, and the analyses 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 results would be analysed in parallel with those of the concurrent International Stroke Trial (IST) of 20 000 patients with acute stroke from other 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 placebo-allocated group (167 [1·6%] vs 215 [2·1%]; 2p=0·01) but slightly more haemorrhagic strokes (115 [1·1%] vs 93 [0·9%]; 2p>0·1). For the combined in-hospital endpoint of death or non-fatal stroke at 4 weeks, there 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 cases per 1000. At discharge, 3153 (30·5%) aspirin-allocated patients and 3266 (31·6%) placebo-allocated patients were dead or dependent, corresponding 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 ischaemic stroke. Taken together, CAST and the similarly large IST show reliably that aspirin started early in hospital produces a small but definite 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).

Introduction

During the current decade in China there will be about 15 million deaths from stroke, plus much disability.1 Although the proportion of haemorrhagic strokes is somewhat higher than in western populations, ischaemic stroke still accounts for the majority of new cases and deaths in China.2, 3 If a simple and widely practicable treatment for acute ischaemic stroke could be shown reliably to produce even a moderate improvement in outcome, the population benefit could be substantial. Aspirin is effective in the treatment of acute myocardial infarction,4 and a systemic overview in 1994 of all previous trials of long-term antiplatelet therapy among patients with a history of previous myocardial infarction, stroke, or transient ischaemic attack showed that about 40 serious vascular events (myocardial infarction, stroke, or vascular death) are avoided per 1000 patients treated for a few years with aspirin.5 As a result, many patients admitted to hospital with strokes are now being discharged on long-term low-dose aspirin (or other antiplatelet agents), not only in western countries,6 but also in China7 and elsewhere.

There is, however, little evidence on the balance of benefits and risks of antiplatelet therapy started during the initial acute phase of ischaemic stroke.8, 9 Consequently, there is much variation in routine clinical practice.6, 7, 10, 11 The large, randomised, placebo-controlled Chinese Acute Stroke Trial (CAST), and the parallel International Stroke Trial (IST)12 conducted in other countries, were designed to provide reliable evidence about the effects on early mortality and major morbidity of early aspirin treatment in a wide range of patients presenting with definite or suspected ischaemic stroke. Both trials planned to enrol 20 000 patients, thereby yielding a total of 40 000.

Section snippets

Eligibility

Patients admitted to the 413 participating hospitals in China were eligible for CAST if they were judged to be within 48 h of the onset of symptoms of suspected acute ischaemic stroke, and had no clear indications for, or contraindications to, aspirin. Contraindications were specified not by the protocol but by the responsible physician, and were generally based on an expectation of either an increased risk of adverse effects (eg, because there was a recent history of serious gastric bleeding

Characteristics of participants

21 106 patients with entry forms available by April, 1997, were enrolled from 413 Chinese hospitals between November, 1993, and March, 1997 (figure 1). This large size ensured good balance between the aspirin and placebo groups for the main prerandomisation prognostic features that were measured (table 1). The mean ages of the aspirin and placebo groups were 63·2 years (SD 10·4) and 63·1 years (10·3) years; the mean times from onset of symptoms were 24·9 h (14·1) and 25·1 h (14·2); and the mean

Discussion

Before CAST and IST12 (which also randomised about 20 000 acute stroke patients), no reliable evidence was available on the value of early antiplatelet therapy in acute ischaemic stroke, and there was particular concern about the potential risk of intracranial haemorrhage.6, 11 These two large trials in about 40 000 randomised patients, together with the non-fibrinolytic component of the smaller MAST-Italy trial,8 show, however, that immediate treatment of acute ischaemic stroke with

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