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Three Part Question

In [patients presenting with symptoms suggestive of a CVA [cerebrovascular accident]] does [the administration of aspirin] prior to CT scan improve [outcome]?

Clinical Scenario

A 67 year-old man with a history of angina presents with a sudden onset of left sided weakness in the early evening. You know that the patient will not receive a CT scan until the following day and that if he is having a cerebral infarction he may receive some benefit from administration of aspirin. You wonder if the potential benefit out-weighs a possible increase in the risk of worsening any intracranial haemorrhage.

Search Strategy

Medline 1966 - 4 July 2006 using the OVID interface:
[exp Cerebrovascular Accident/ OR stroke$.mp. OR cerebrovascular accident$.mp.] AND [aspirin.mp. OR exp Aspirin/ OR acetylsalicylic acid.mp. OR ASA.mp.] AND [acute.mp. OR exp Acute Disease/ OR emergen$.mp. OR urgent.mp. OR immediate.mp.] limit to humans and English language.
The Cochrane Database of Systematic Reviews, within the Cochrane Library Issue 3, 2006:
(MeSH Cerebrovascular Accident OR stroke) AND (MeSH Aspirin OR aspirin).
734 papers were found in Medline and 132 in the Cochrane Database of Systematic Reviews. One paper was a combined analysis with relevance to the question. There was also one Cochrane systematic review with relevance to the question.

Search Outcome

One combined analysis paper and one Cochrane Review with relevance to the question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Chen et al, 2000, UK	Combination of 20,000 patients from the Chinese Acute Stroke Trial and 20,000 patients from the International Stroke Trial presenting with acute stroke symptoms.	Prospectively planned meta-analysis of data to assess benefits and risks of aspirin in particular sub-groups of patients including those without a CT scan.	Recurrent ischaemic stroke in all patients	Reduction of 7 per thousand patients.(P<0.0000005)
			Mortality without further stroke	Reduction of 4 per thousand patients (P=0.025)
			Haemorrhagic stroke or haemorrhagic transformation of infarct	Increase of 2 per thousand patients.(P=0.035)
			Benefit/hazard in patients randomized without CT scan	No significant difference in outcome in 9,000 patients compared to patients with CT scan prior to randomization.
			Benefit/hazard in patients inadvertently randomized after shown to have had haemorrhagic stroke	No significant difference in outcome in 773 patients.
			Combined outcome of further stroke or death	Reduction of incidence of 9 per thousand patients.
Sandercock et al, 2003 Scotland, UK	Randomised trials comparing antiplatelet therapy (started within 14 days of the stroke) with control in patients with definite or presumed ischaemic stroke. Total of 9 trials with 41,399 patients.	Review of randomised trials.	Outcome of patients with intracerebral haemorrhage inadvertently randomised to receive aspirin	Significant reduction in odds of poor outcome (OR = 0.68; 95% CI 0.49 to 0.94)

Comment(s)

In many hospitals in the UK, patients who attend with symptoms and signs suggestive of a cerebrovascular event will not undergo an immediate computed tomography scan outside of normal working hours. Several patients therefore have to wait for a long time before the underlying diagnosis is made and appropriate treatment is given. Most of these patients will have had a cerebral infarction, and are likely to benefit from antiplatelet treatment. The concern with giving all patients blind treatment is the risk of causing further bleeding in the event of a cerebral haemorrhage. Most patients from studies reported in the Cochrane review and all patients in the combined analysis were taken from two large randomised trials, the International Stroke Trial and the Chinese Acute Stroke Trial. Although neither of these trials sought to answer the above-mentioned question directly, both trials inadvertantly incorporated these patients as a subgroup. It was shown that aspirin improved the outcome in patients who had not undergone computed tomography and also in patients who were shown to have a haemorrhagic stroke. Although treating patients who present with symptoms of a cerebrovascular event with aspirin increases the risk of intracranial haemorrhage, there is an overall benefit in terms of survival and recurrent stroke rates. Patients shown to have an intracerebral haemorrhage on computed tomography scan were also overall benefited from receiving aspirin. These studies were based on starting aspirin within 48 h of resentation. No data were available on giving aspirin immediately at the time of presentation. As a word of caution, an observational study by Toyoda et al suggested that prior treatment with aspirin may be an independent predictor of haematoma enlargement in patients with intracranial haemorrhage (odds ratio 5.02, 95% confidence interval 1.42 to 17.7). It may therefore be prudent to withhold aspirin treatment if a computed tomography scan is to be carried out within 48 h of presentation.

Clinical Bottom Line

Administration of aspirin is likely to benefit most patients overall, perhaps even those with haemorrhagic strokes. Available data demonstrate a benefit only to patients starting treatment with aspirin within 48 h of admission, and no data suggests increased benefit with earlier administration. If a computed tomography scan is to be carried out within 48 h of presentation, then it would be prudent to withhold antiplatelet treatment until the underlying pathology is shown. Those patients who are likely to improve the most will still benefit from administration of treatment at this point.

References

1. Chen ZM. Sandercock P. Pan HC. Counsell C. Collins R. Liu LS. Xie JX. Warlow C. Peto R. Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the Chinese Acute Stroke Trial and the International Stroke Trial. Stroke 2000;31(6) 1240-9.
2. Sandercock P; Gubitz G; Foley P; Counsell C. Antiplatelet therapy for acute ischaemic stroke. The Cochrane Database of Systematic Reviews 2003 2003; Issue 2 Art No: CD000029.
3. Toyoda K; Okada Y; Minematsu K; Kamouchi M; Fujimoto S; Ibayashi S; Inoue T. Antiplatelet therapy contributes to acute deterioration of intracerebral haemorrhage Neurology 2005; 65(7): 1000-1004