Anticoagulants versus antiplatelet agents for acute ischaemic stroke

Treatment with anticoagulants offers no net advantages over antiplatelet agents in patients with acute ischaemic stroke. Ischaemic stroke is caused by a blood-clot blocking the blood supply to an area of the brain. Blood-thinning drugs, such as anticoagulants and antiplatelet agents, can potentially prevent arteries from being blocked, or prevent them re-blocking. They can also prevent clots forming in the deep veins in the leg, which can break off and travel to the lungs. However, such drugs can also cause bleeding complications, which might offset any benefits. Antiplatelet agents (mainly aspirin) are associated with long-term benefits and have become standard treatment for acute ischaemic stroke. This review aimed to test whether any anticoagulant regimen offers net advantages over antiplatelet agents, overall, or in specific categories of patients. There was no evidence that anticoagulants are superior to antiplatelet agents (in fact, anticoagulants caused a small increase in the number of deaths at long-term follow-up). However, the combination of low-dose anticoagulant and aspirin seemed to offer benefits over aspirin alone, and the combination should be investigated further.

Authors' conclusions: 

Anticoagulants offered no net advantages over antiplatelet agents in acute ischaemic stroke. The combination of low-dose UFH and aspirin appeared in a subgroup analysis to be associated with net benefits compared with aspirin alone, and this merits further research.

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Background: 

Antiplatelet agents produce a small, but worthwhile benefit in long-term functional outcome and survival, and have become standard treatment for acute ischaemic stroke. Anticoagulants are often used as an alternative treatment, despite evidence that they are ineffective in producing long-term benefits. We wanted to review trials which have directly compared anticoagulants and antiplatelet agents, to assess whether any anticoagulant regimen offers net advantages over antiplatelet agents, overall or in some particular category of patients (e.g. patients with atrial fibrillation).

Objectives: 

To assess: (1) the effectiveness of anticoagulants compared with antiplatelet agents in acute ischaemic stroke, and (2) whether the addition of anticoagulants to antiplatelet agents offers any net advantage over antiplatelet agents alone.

Search strategy: 

We searched the Cochrane Stroke Group Trials Register, the Cochrane Controlled Trials Register, the trials register held by the Antithrombotic Therapy Trialists' Collaboration, MEDLINE (1966 to 2000), and EMBASE (1980 to 2000). All searches were performed during April and May 2001.

Selection criteria: 

Truly unconfounded, randomised-controlled trials comparing anticoagulants with antiplatelet agents, or anticoagulants and antiplatelet agents with antiplatelet agents alone, given within 14 days of onset of presumed or confirmed ischaemic stroke.

Data collection and analysis: 

Both reviewers independently selected trials for inclusion in the review, assessed trial quality and extracted data.

Main results: 

A total of 16,558 patients from four trials contributed to the analyses. The methodological quality was high in all four trials. The anticoagulants tested were unfractionated heparin (UFH) and low molecular-weight heparin. Aspirin was used as control in all trials. Overall, there was no evidence that anticoagulants were superior to aspirin in reducing 'death or dependency' at long-term follow-up (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.98 to 1.15). Compared with aspirin, anticoagulants were associated with a small but significant increase in the number of deaths at the end of follow-up (OR 1.10, 95% CI 1.01 to 1.29), equivalent to 20 more deaths (95% CI 0 to 30) per 1000 patients treated; a significant increased risk of symptomatic intracranial haemorrhage (OR 2.35, 95% CI 1.49 to 3.46); and a non-significant increased risk of 'any recurrent stroke' during treatment (OR 1.20, 95% CI 0.99 to 1.46). These neutral or adverse effects outweighed a small, but significant effect on symptomatic deep vein thrombosis (OR 1.20, 95% CI 0.07 to 0.58), equivalent to 10 fewer (95% CI 0 to 30) DVTs by 14 days per 1000 patients treated with anticoagulants instead of aspirin. Subgroup analysis could not identify any type, dose, or route of administration of anticoagulants associated with net benefit, or any benefit in patients with atrial fibrillation. Overall, the combination of UFH and aspirin did not appear to be associated with a net advantage over aspirin alone. A subgroup analysis showed that, compared with aspirin, the combination of low-dose UFH and aspirin was associated with a marginally significant reduced risk of 'any recurrent stroke' (OR 0.75, 95% CI 0.56 to 1.03) and a marginally significant reduced risk of death at 14 days (OR 0.84, 95% CI 0.69 to 1.01), and with no clear adverse effect on death at end of follow-up (OR 0.98, 95% CI 0.85 to 1.12).

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