In a presentation titled “So what have I learned from the latest carotid trials?” Michael R Jaff, associate professor of Medicine Harvard Medical School, told delegates at the CX@LINC 2011 symposium that it never ceases to amaze him how physicians do not agree on the interpretation of results even when presented with the highest levels of scientific evidence, i.e., multicentre randomised clinical trials which have met their primary endpoint.
Jaff, who is also medical director, Vascular Center, Massachusetts General Hospital, Boston, Masachussets, USA, told delegates, “After all, CREST is a randomised multicentre trial done under the most stringent criteria with tremendous independent oversight, every step of the way. The predefined primary endpoint was agreed upon not only by the federal government in the USA and its steering committee, but by many national societies who care for patients with vascular disease. Before the first patient was enrolled, a vascular surgeon ran this trial. Ultimately, the primary endpoint was met. How could this be confusing? It should have settled the debate”, he insisted.
At the Leipzig Interventional Course 2011, Leipzig, Germany, Jaff told delegates that the current evidence showed that for a patient with carotid artery disease, carotid endarterectomy, when performed bskilled surgeons with an excellent track record, is an effective option, which may be more effective in older patients. Similarly, carotid artery stenting when performed by skilled interventionists is effective, and may be more effective in younger patients.” He also talked about a third option; medical therapy. “Medical therapy has not been tested specifically in the patients being considered for carotid revascularisation in a rigorous study. Comprehensive medical therapy must still be tested head-to-head with revascularisation, but the impact of medical therapy is likely improving,” he said.
Jaff pointed to the interim safety analysis of the International Carotid Stenting Study (ICSS) comparing carotid artery stenting with endarterectomy in patients with symptomatic carotid stenosis found that risks of any stroke (65 vs 35 events; HR 1·92, 1·27—2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. The ICSS safety analysis was published in The Lancet (March 2010) and investigators wrote in the interpretation that “Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.”
However, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) results, published in May 2010 in NEJM, showed that on the composite primary end point of any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke on follow-up, stenting was associated with a 7.2% rate of these events vs. 6.8% with surgery, a non-significant difference.
So Jaff asked: “Why did CREST not settle the score?” He stated that the reason for this was that surgeons feel that carotid revascularisation is performed in order to prevent stroke. Carotid endarterectomy reduced the stroke risk more than carotid artery stenting did. Also, surgeons saw the excess myocardial infarction rate with carotid endarterectomy as “less of an issue”. On the other hand, Jaff pointed out that interventionists felt that CREST data showed that carotid artery stenting was performed as safely as carotid endarterectomy, and that the excess stroke risk was due to an increase in minor strokes only. They also felt that the myocardial infarction risk associated with carotid endarterectomy was important. Neurologists feel that although outcomes were low, medical therapy is more effective than any form of revascularisation.
The accompanying editorial in The New England Journal of Medicine published in May 2010 stated, “Though it appears that the increased risk of stroke with carotid-artery stenting is offset by an increased risk of myocardial infarction with carotid endarterectomy, stroke has greater long-term health consequences than myocardial infarction.” So, this is the issue, said Jaff. Should myocardial infarction have been included as a component of the primary endpoint. Many physicians believe that the apparent equivalence of carotid artery stenting and carotid endarterectomy in the CREST results might be as a result of equating stroke with myocardial infarction (both of which are in the composite primary end point) even though these may impact a patient’s life in very different ways.
Jaff also touched on the latest carotid artery stenting data available, which shed some light on the issue of operator experience which is critical to the success of either carotid artery stenting or carotid endarterectomy. “The major adverse events rate as shown by CASES PMS (Carotid Artery Stenting With Emboli Protection Surveillance–Post-Marketing Study) vs SAPPHIRE shows that with short formalised training programmes, physicians with significant experience in carotid stenting can achieve similar short- and longer-term results to the highly experienced SAPPHIRE investigators. Published in the Journal of American College of Cardiology, this analysis shows that at one-year, the results of carotid artery stenting with embolic protection carried out by operators of significant experience is equivalent to the results of carotid artery stenting carried out by experienced SAPPHIRE investigators and significantly better than outcomes with carotid endarterectomy.
“Can one actually predict the stroke risk in patients with asymptomatic carotid artery stenosis?” questioned Jaff. He referred to recent research which finds that for asymptomatic carotid disease, high-intensity transient signals (HITS) seen during transcranial Doppler assessment may be a significant marker of future stroke risk. Asymptomatic embolization for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study published in Lancet Neurology in 2010, shows that detection of embolic signals by transcranial doppler may identify groups of patients with asymptomatic carotid stenosis who are at high risk of future stroke. Authors report that this technique might be a useful risk predictor for identifying those patients who might benefit from intervention with carotid endarterectomy.
“I think what we have learned in the recent data is we have two excellent procedures to offer our patients with carotid disease. The debate should not be which one is necessarily better than the other, but rather which one is right for the individual patient now that we have this data,” he concluded.