Oral antiplatelet therapy for acute ischaemic stroke
Abstract
Background
In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the brain. Such damage gives rise to the symptoms of stroke. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and also reduce the risk of early recurrent ischaemic stroke, thereby reducing the risk of early death and improving long‐term outcomes in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage.
Objectives
To assess the efficacy and safety of immediate oral antiplatelet therapy (that is started as soon as possible and no later than two weeks after stroke onset) in people with acute presumed ischaemic stroke.
Search methods
We searched the Cochrane Stroke Group Trials Register (last searched 16 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2013), MEDLINE (June 1998 to May 2013), and EMBASE (June 1998 to May 2013). In 1998, for a previous version of this review, we searched the register of the Antiplatelet Trialists' Collaboration, MedStrategy and contacted relevant drug companies.
Selection criteria
Randomised trials comparing oral antiplatelet therapy (started within 14 days of the stroke) with control in people with definite or presumed ischaemic stroke.
Data collection and analysis
Two review authors independently applied the inclusion criteria and assessed trial quality. For the included trials, they extracted and cross‐checked the data.
Main results
We included eight trials involving 41,483 participants. No new trials have been added since the last update.Two trials testing aspirin 160 mg to 300 mg once daily, started within 48 hours of onset, contributed 98% of the data. The risk of bias was low. The maximum follow‐up was six months. With treatment, there was a significant decrease in death or dependency at the end of follow‐up (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91 to 0.99). For every 1000 people treated with aspirin, 13 people would avoid death or dependency (number needed to treat 79). Antiplatelet therapy was associated with a small but definite excess of symptomatic intracranial haemorrhages, but this small hazard was significantly outnumbered by the benefit, the reduction in recurrent ischaemic stroke and pulmonary embolus.
Authors' conclusions
Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who cannot swallow) and started within 48 hours of onset of presumed ischaemic stroke, reduced the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications; long‐term outcomes were improved.
PICOs
Plain language summary
Oral antiplatelet therapy for acute ischaemic stroke
Question
We wanted to compare the safety and effectiveness of oral antiplatelet therapy versus placebo or no treatment in people with acute ischaemic stroke to see if oral antiplatelet drugs reduced the number of deaths and improved the long‐term outcomes in survivors.
Background
Most strokes are caused by a sudden blockage of an artery in the brain that is usually due to a blood clot (called an ischaemic stroke). Immediate treatment with antiplatelet drugs such as aspirin may prevent new clots from forming and hence improve recovery after stroke. However, antiplatelet drugs may also cause bleeding in the brain, which could offset any benefits.
Study characteristics
We identified eight studies, up to October 2013, for inclusion in the review. These studies included a total of 41,483 participants. Two of the studies contributed 98% of the data. Four studies tested aspirin, three studies tested ticlopidine and one study tested aspirin plus dipyridamole. The majority of participants in the review were elderly, with a significant proportion over 70 years of age. Males and females were almost equally represented in the trials. There appeared to be some variation in stroke severity among the included trials. The scheduled duration of treatment varied from five days to three months and the scheduled follow‐up period varied from 10 days to six months.
Key results
Aspirin, at a dose of 160 mg to 300 mg daily started within 48 hours of the onset of stroke symptoms, saved lives and reduced the risk of further stroke occurring in the first two weeks. If treatment was started more than 48 hours after onset but within 14 days, the limited evidence from this review and other external data suggests that aspirin is of benefit even starting at this late stage. Aspirin also increased the chances of being alive and independent and improved the chances of making a complete recovery from the stroke. The risk of serious bleeding was very low. Almost all the evidence in this review comes from trials of aspirin. There is no reliable evidence on the effects of the other oral antiplatelet drugs in acute stroke that were assessed in this review (clopidogrel, ticlopidine, cilostazol, satigrel, sarpolgrelate, KBT 3022, iisbogrel).
Quality of the evidence
The quality of the evidence contributing to these results was generally good.
