• 
• 

Three Part Question

In [a patient presenting with TIA] is [Aspirin or Clopidogrel] better [for secondary prevention of stroke]?

Clinical Scenario

My FY1 who had just seen a patient with a TIA was told by the stroke specialist nurse to prescribe clopidogrel. The FY1 had already given the patient aspirin and asked me whether clopidogrel was better for secondary prevention in this group of patients, and also should she give the clopidogrel as well as the aspirin?

Search Strategy

Search using NLH Search 2.0 Medline 1950-Present & EMBASE 1980-Present.
[exp aspirin OR ASA OR acetylsalcylic acid] AND [exp clopidogrel OR plavix OR thienopyridine$] AND [TIA OR exp Transient Ischaemic Attack OR Transient Ischemic Attack OR exp Mini Stroke$ OR Ischaem$ Or Ischem$ OR Stroke OR CVA]ti.ab LIMIT to human

Search Outcome

160 papers identified of which only one directly addressed the question. Other trials compared the efficacy of combinations of anti-platelet drugs such as aspirin and dipyridamole versus clopidogrel (no difference in efficacy) and aspirin plus clopidogrel versus aspirin alone (possibly better at prevention but also possibly higher risk of intra cranial bleed).

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Gent M. November 1996 International	384 centres in USA, Europe, and Australia.6431 patients with recent ischaemic stroke (including retinal and lacunar infarction) likely to be of atherothrombotic origin.	Randomised, blinded trial comparing relative efficacy of clopidogrel and aspirin in reducing the risk of ischaemic stroke, myocardial infarction and vascular death.	Non-fatal ischaemic stroke	Clopidogrel 472 Aspirin 504	None really, well organised trial.
			Fatal schaemic stroke	Clopidogrel 37 Aspirin 42
			Non-fatal primary ICH	Clopidogrel 14 Aspirin 24
			Haemorrhagic death	Clopidogrel 23 Aspirin 27

Comment(s)

Stroke prevention regimes have varied between different trusts I have worked in. The vast majority though are using aspirin as a "first line" after TIA events diagnosed in the ED. The evidence from the well run trial of aspirin versus clopidogrel seems to show a slight impovement in outcome with clopidogrel with a relative risk reduction of 7.3% (95% CI -5.7 to 18.7) of clopidogrel over aspirin in the stroke subgroup and a relative risk reduction of 8.7% (95% CI 0.3 to 16.5) in all groups for all outcomes not just stroke. Current guidelines from The European Stroke Organisation recommend aspirin AND dipyridamole OR clopidogrel for secondary prevention, not advocating the use of aspirin alone for secondary prevention of stroke. NICE releeased a technology appraisal guidance in 2010 on the use of aspirin,dipyridamole and clopidogrel. The appraisal basically recommended clopidogrel or aspiri+dipyridamole for secondary prevention of stroke but also stated that clopidogrel is NOT licensed for use after TIA.

Clinical Bottom Line

From the available evidence clopidogrel may have a slightly better efficacy than aspirin alone in secondary prevention of stroke, although it is not licensed for this use, local guidelines should be followed.

References

1. Gent M A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) Lancet November 1996, vol./is. 348/9038(1329-1339)
2. Hankey GJ,Sudlow CL,Dunbabin DW Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database of Systematic Reviews 2000, vol./is. /2(CD001246)