Carotid Artery Stenting With and Without Cerebral Protection
To the Editor:
We note with interest the finding from the EVA-3S Trial of carotid stenting that the rate of stroke within 30 days of treatment appeared to be higher in patients who were stented without the use of protection device.1 However, we are surprised that the Safety Committee recommended that all patients should be treated with a protection device, although the difference between treatment with and without protection did not reach statistical significance. Moreover, the report does not state whether there were any differences between the two groups in the indications for stenting, the nature of the stenosis, or difficulty of access. Any of these could have led to the decision to stent without protection and at the same time increase the risk of procedural stroke. In the EVA-3S report, age was significantly different between patients treated with and without cerebral protection (66.0 versus 72.7 years, P=0.013).1 Age has been reported to be a risk factor for carotid stenting2 and this could explain the worse outcome in patients treated without a protection device. There was also a threefold increase in the proportion of patients treated by predilation in the protected group, which might contribute to their better outcome. Only strokes at the time of the procedure would be expected to be prevented by protection devices. In the EVA-3S, only 2 strokes occurred on the day of the procedure without protection, compared with 3 strokes in those treated with cerebral protection. Such a difference could well have arisen by chance. For all these reasons, we believe the recommendation of the EVA-3S Steering Committee was premature. On the other hand, we accept that ethical and research governance considerations may make it difficult to continue a treatment that appears to have a greater risk before the difference reaches statistical significance.
No protection devices were used in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) where the rate of stroke within 30 days of treatment was 10% in patients treated with angioplasty or stenting.3 In the EVA-3S report, the same measure in patients treated with cerebral protection was 10.3%.1 There is therefore no clear evidence that protection reduces the rate of stroke. Thus, we are not convinced that the evidence presented mandates the use of protection devices. Moreover, there are those who argue that protection devices are unnecessary and may increase the risks in some patients.
The protocol for the International Carotid Stenting Study (ICSS or CAVATAS 2) states that when a patient is having stent placement “a cerebral protection system should be used whenever the operator thinks one can be safely deployed.”4 The editorial accompanying the EVA-3S report recommends that ICSS should do an interim analysis of protected versus nonprotected patients.1 The ICSS investigators have subsequently presented confidential data on the outcome of stenting with and without protection devices in ICSS to the Data Monitoring Committee. The Data Monitoring Committee acknowledged the need to keep monitoring this issue in future annual reports, but did not recommend any protocol modifications. At present the ICSS investigators have complete data returns for 78 completed stenting procedures of which 66 (85%) were carried out with some form of cerebral protection. The sample of unprotected procedures is very small1,2⇓ and this fact alone can bias any safety data. To take a theoretical example, in an existing series of 10 procedures with 1 stroke, a single stroke in the next procedure would almost double the apparent rate of complications.
In conclusion, we believe that the data from the EVA-3S Trial should be treated very cautiously because of the small numbers of patients analyzed. We do not believe that the current protocols of the other carotid stenting trials need modification.
Mathur A, Roubin GS, Iyer SS, Piamsonboon C, Liu MW, Gomez CR, Yadav JS, Chastain HD, Fox LM, Dean LS, Vitek JJ. Predictors of stroke complicating carotid artery stenting. Circulation. 1998; 97: 1239–1245.
Featherstone RL, Brown MM Coward LJ, for the ICSS Investigators. International Carotid Stenting Study (ICSS): protocol for a randomised clinical trial comparing carotid stenting with endarterectomy in symptomatic carotid artery stenosis. Cerebrovascular Diseases. 2004; 18: 69–74.