Interventional Perspectives on Carotid Stenting – Examining the Trial Data
Table 1: Carotid Artery Stent – Negative Trial Results and Their Meaning
Trial
Leicester Wallstent EVA-3S SPACE ICSS
Result 5/7 CVA
12 versus 4.5% 9.6 versus 3.9% 6.84 versus 6.34% 8.5 versus 5.1
CVA = cerebrovascular accident; EP = embolic protection.
compared with CEA. The SPACE study used a distal protection device in only 27% of the patients; this study was terminated for financial reasons but not because of any safety signal. The published results show no difference in outcomes between the stent and surgery groups. The more recent International Carotid stenting study (ICSS)25
showed inferior
results for symptomatic patients treated with CAS and distal protection compared with those treated with CEA. All of these studies together had a negative impact (see Table 1) on the widespread use of CAS and enrolment in ongoing clinical trials.
It is important to remember that no single trial provides all the answers. Some are designed to provide answers based on theories and assumptions that were prevalent at the time of the study design. Many of these trials had no mandated CAS device training or an adequate roll-in period to make sure the learning curve had peaked by the start of the study and distal protection was not mandated with a uniform device system. Sometimes, the medical therapy was not contemporary; for example, dual antiplatelet agents were not uniformly used.
Training Matters
It is axiomatic that the more procedures we perform, the better we perform them; we do not need randomised studies to prove this point. It is essential that the operator is trained and his or her results vetted by an independent interventional committee before the operator is allowed to enter the roll-in phase prior to randomisation. The operator must have adequate expertise in the device being tested. With that in mind, the requirements for endovascular experience in the three European trials are as follows:
•
SPACE: Minimum of 25 cases, but proctored training allowed for those who had performed only 10 lifetime cases. This did not have to be recent experience or concurrent.
• EVA 3S: At least 12 procedures or at least 30 supra-aortic (sub-clavian) procedures. Tutor-assisted procedures allowed at certain centres not fulfilling the minimum requirements. A significant number of procedures in the trial were the first ever procedures performed by trainees.
•
ICSS: At least 50 stenting procedures, 10 of which had to be carotid stenting. Tutor-assisted procedures allowed for sites with limited experience.
Contrast this with the CREST trial enrolment requirements. An independent interventional committee evaluated each operator’s experience. The results were reviewed and a minimum of 20 carotid stent procedures were required with acceptable stroke and death rates meeting AHA criteria. CREST had an elaborate roll-in programme, with almost 1,400 patients enrolled in the roll-in phase – more than the number of stent patients enrolled in any of the European trials. The roll-in phase shows clearly the role of training
INTERVENTIONAL CARDIOLOGY Meaning
Experience, technology Experience, technology, EP Experience, technology, EP Experience, age Experience, EP
Major stroke versus none
Minor stroke verus none
MI versus none
Figure 8: Carotid Revascularization Endarterectomy versus Stent Trial Short Form 36
Physical component scale Mental component scale
-30 -20 -10 0 10 20
-20 Difference
Impact of periprocedeural events (stroke/MI) on Short Form 36 (SF-36) at one year adjusting age, sex, symptomatic cerebrovascular disease and baseline SF-36 measures – growth curve modelling.
MI = myocardial infarction.
Figure 9: Carotid Revascularization Endarterectomy Versus Stent Trial Quality Short Form 36 Patient Perception of CREST Trial
CAS superior Primary end-point
Stroke + death end-point Stroke end-point
MI end-point Any death Any stroke
Major ipsi stroke
Major non-ipsi end-point Minor ipsi stroke
Minor non-ipsi end-point Cranial nerve palsy
0.01 0.1 1 Hazard ratio (log scale)
CAS = carotid artery stenting; CEA = carotid endarterectomy; MI = myocardial infarction. Figure 10: Primary Outome at Four Years
4 P interaction = 0.020 3 CEA superior 2 1 CAS superior 0 40 50 60 Age (years) CAS = carotid artery stenting; CEA = carotid endarterectomy.
and outcomes when individual outcomes are compared within the specialties, suggesting that cardiologists with early adoption of embolic protection have learned how to troubleshoot far more quickly than non-cardiologists in asymptomatic patients stratified by age. Roffi et al. elegantly highlight the conundrum by stating that tutoring and randomised trials should be considered mutually exclusive.26
No
surgeon would be allowed to enrol in a randomised trial if he or she had performed only 10 endarterectomy procedures.
79 70 80 90 10 CEA superior
-10
0
10
20
Hazard ratio
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