Published online before print October 6, 2005, doi: 10.1161/01.STR.0000185652.46979.f6
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(Stroke. 2005;36:2340-a.)
© 2005 American Heart Association, Inc.
Letters to the Editor |
Transcranial Doppler and Carotid Artery Disease Strokes: More Than Just Risk Stratification
Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
Coventry and Warwickshire County Vascular Unit, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
To the Editor:
Two important studies addressing the role of transcranial Doppler ultrasound (TCD) microemboli detection and stroke prevention have been published recently.1,2 Markus and MacKinnon1 studied 200 patients within 3 months of a focal neurological event. Their study demonstrated that the presence of microembolic signals detected during 1 hour of TCD monitoring was an independent predictor of future stroke and transient ischemic attack (TIA). Two major implications were proposed, first that TCD emboli detection could be useful for risk stratification in patients with carotid stenosis and, second, that the technique could be used to assess the efficacy of antithrombotic therapy. In the recently published Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial,2 dual antiplatelet therapy (aspirin plus clopidogrel) resulted in more effective control of microembolic signals than single antiplatelet therapy (aspirin alone). There was an associated reduction in the subsequent prevalence of TIAs and strokes.
Similar conclusions were drawn by the authors of both studies, in particular those patients with recent symptoms and emboli should be operated on urgently "wherever possible." However, a recent systematic review of the risks of carotid endarterectomy in relation to both the clinical indication for and timing of surgery has shown that urgent carotid surgery carries a much higher risk (19.2%; 95% CI, 10.7 to 27.8) than elective surgery (odds ratio, 3.9; 95% CI, 2.7 to 5.7; P<0.001; 13 studies).3
Immediately after a TIA or stroke, there is a rise in TCD-detected micoembolic signals. Those patients who continue to embolize are at greater risk of an additional neurological event.4 Recurrent or crescendo TIA patients represent a particularly high-risk group. It is possible to stop both emboli and additional symptoms in these patients with TCD-directed IV antiplatelet agents, with the dose being incrementally increased until the micoemboli cease. Consequently, it is possible to influence the timing of surgical intervention, allowing patients to undergo carotid endarterectomy safely on the next elective list,5 avoiding the risks associated with urgent or emergency surgery3 or the risks associated with delay6 in patients whose microemboli persist despite oral antiplatelet therapy.1,2,4
In the study by Markus and MacKinnon,1 the time between index event and assessment was considerably >72 hours in most of the subjects examined. This leads to the conclusion that some reported strokes could have been prevented. We believe that earlier assessment would show a stronger beneficial influence of TCD-directed antithrombotic therapy followed by surgery when necessary. Microemboli are surrogate markers for the risk of future embolic events. The pharmacological efficacy of therapeutic interventions can now be assessed rapidly, noninvasively, and inexpensively. TCD emboli detection appears to offer an important advance enabling the optimal integration of both medical therapy and the timing of surgery, and the technique should be more widely available.
References
1. Markus HS, MacKinnon AM. Asymptomatic embolization detected by Doppler ultrasound predicts stroke risk in symptomatic carotid artery stenosis. Stroke. 2005; 36: 971–975.
2. Markus HS, Droste DW, Kaps M, Larrue V, Lees KR, Siebler M, Ringelstein EB. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using Doppler embolic signal detection. Circulation. 2005; 111: 2233–2240.
3. Bond R, Rerkasem K, Rothwell PM. Systematic review of the risks of carotid endarterectomy in relation to the clinical indication for and timing of surgery. Stroke. 2003; 34: 2290–2301.
4. Slikwa U, Lingau L, Stohlmann WD, Schmidt P, Mull P, Diel RR, Noth J. Prevalence and time course of microembolic signals in patients with acute stroke. Stroke. 1997; 28: 358–363.
5. Lennard NS, Vijayasekar C, Tiivas C, Chan CWM, Higman DJ, Imray CHE. Control of emboli in patients with recurrent or crescendo transient ischaemic attacks using preoperative transcranial Doppler-directed Dextran therapy. Br J Surg. 2003; 90: 166–170.[CrossRef][Medline] [Order article via Infotrieve]
6. Coull A, Lovett J, Rothwell P, on behalf of the Oxford Vascular Study. Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public organization of services. BMJ. 2004; 328: 326–328.
Response:
St. George’s Hospital Medical School, London, UK
St. George’s University of London, London, UK
Like Pattinson and Imray, we agree that Doppler embolic signal detection shows great promise in identifying patients with symptomatic carotid stenosis at high risk of early recurrent stroke. This group of patients may well benefit from more aggressive antiplatelet therapy. It is also possible that the use of the technique, combined with more aggressive antiplatelet therapy to reduce embolization in active embolizers, could allow carotid endarterectomy to be delayed in some patients.
However, based on considerable current evidence, patients with stable symptomatic carotid stenosis should be operated on as soon as possible. It has been clearly shown from analysis from the ECST and NASCET trials that the stroke risk in the first 2 weeks is very high.1 The metaanalysis that the authors quote showed no difference in the odds of stroke and death after early carotid endarterectomy for established stroke compared with late surgery.2 The excess risk was only seen in the smaller group of patients with unstable symptoms, ie, progressing stroke or crescendo transient ischemic attacks (TIAs). Therefore, in the majority of patients with a single ischemic TIA, or stroke with small infarct, current evidence suggests that carotid endarterectomy should be performed as soon as possible. In the more unstable patient with progressing symptoms, crescendo TIAs, or a large infarct, transcranial Doppler may well be useful in guiding treatment to allow stabilization before elective surgery. It may also be useful in guiding treatment in patients with stable symptoms and TIA or minor stroke in the many units worldwide where endarterectomy cannot be performed immediately as a result of logistic and resource issues.
In addition, before recommending its widespread implementation, some caution is required. Ideally, it should be shown in a large clinical study that this approach, when implemented on a widespread clinical scale, does allow stroke to be prevented. This will depend not only on the ability of embolic signals to predict stroke, as we have recently demonstrated, but also on the ability of clinical units to reliably implement the technique, including evaluation for embolic signals in real time. Current research studies, such as the 2 cited by Pattinson and Imray,3,4 have used assessment of the presence of embolic signals at a later date by a single experienced observer on data stored on digital audiotapes.
References
1. Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ; Carotid Endarterectomy Trialists Collaboration. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet. 2004; 363: 915–924.[CrossRef][Medline] [Order article via Infotrieve]
2. Bond R, Rerkasem K, Rothwell PM. Systematic review of the risks of carotid endarterectomy in relation to the clinical indication for and timing of surgery. Stroke. 2003; 34: 2290–2301.
3. Markus HS, MacKinnon AM. Asymptomatic embolization detected by Doppler ultrasound predicts stroke risk in symptomatic carotid artery stenosis. Stroke. 2005; 36: 971–975.
4. Markus HS, Droste DW, Kaps M, Larrue V, Lees KR, Siebler M, Ringelstein EB. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using Doppler embolic signal detection. Circulation. 2005; 111: 2233–2240.
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