This study, using a large population-based database from recent years, shows that when accounting for symptom status and medical high risk criteria (including concurrent cardiac procedures), carotid stenting has a higher risk of combined stroke or death, as well as death and stroke alone compared to carotid endarterectomy in the general US population. High risk status was associated with worse outcome for CEA compared to non-high risk. Outcomes with CAS, however, were not improved in high risk patients compared to CEA.
CMS reimbursement for CAS for symptomatic high risk patients was based in part on the results of a randomized trial showing similar stroke and death rates but a lower rate of a combined endpoint of stroke, death, or MI with CAS versus CEA9
as well as on a historic control made up of patients undergoing concomitant CEA and CABG.16
Our study suggests that these results are not reflective of current national outcomes. The SAPPHIRE trial showed a stroke or death rate of 5.5% for CAS versus 8.5% for CEA (P =.36) at one year (30-day mortality 1.2% vs. 2.5%, P = .39 and 30-day stroke 3.6% vs. 3.1%, P = .77).9
Subsequent randomized trials in average risk patients have shown conflicting results. They have shown either increased stroke and death with CAS or similar results between the two repair methods but with a failure to meet non-inferiority.16,10-12,17
The recently presented CREST trial showed similar rates of stroke, death, and MI in symptomatic and asymptomatic patients with very low event rates in both the CAS and CEA groups. Stroke was lower with CEA while MI was lower with CAS. While this demonstrates the efficacy of CAS in selected patients treated by experienced physicians and supports the prior literature demonstrating a lower stroke rate with CEA, our study suggests that similar results may not be duplicated nationally.17
As an important note, there were strict criteria for interventionalists participating in CREST. They required prior performance of at least 35 carotid stent cases with a subsequent roll-in phase where 10 CAS were performed under supervision. Only physicians with adequate outcomes were invited to participate in the study.13
Wennberg et al. previously demonstrated that mortality after CEA was substantially higher in Medicare patients compared to patients enrolled in NASCET and ACAS, even if their CEA was performed in the same institutions participating in the trials.18
Our findings suggest that this increased mortality may be due to procedures performed in select high risk patients. Our national analysis suggests that mortality rates with CEA in non-high risk patients compares favorably with NASCET (1.0% vs. 0.6%) and ACAS (0.1% vs. 0.1%) suggesting these results are generalizable.19,20
CEA in high risk patients shows increased mortality and stroke/death compared to average risk, however, CAS outcomes were worse than CEA for both high and average risk patients. It is certainly possible that our high risk criteria may not detect true high risk status in some CAS patients and may also overestimate high risk in CEA patients. The lack of specificity of ICD-9 coding unfortunately means our definition of high risk is overestimated in general. However, CEA in high risk patients was associated with improved outcome compared to CAS in non-high risk patients. While these limitations hinder our ability to draw strong conclusions about the safety of CAS, the strongest conclusion to be drawn is that average risk patients undergoing CEA fare reasonably well.
These data suggest that further careful analysis should be made to be certain that the efficacy demonstrated in randomized trials with carefully selected patients being treated by highly trained physicians is translated into effectiveness with similar results in broad general practice.
Prior analyses using the NIS database as well as the SVS registry did not account for high risk status.21-24
Our analysis demonstrates the disparate outcomes in these groups for carotid revascularization and demonstrates need for this stratification for any future comparisons of these procedures. The NIS database is hampered by a questionable ability to discriminate preoperative stroke from a postoperative complication and the potential to underestimate preoperative symptomatic status. We defined symptom status by ICD-9 coding for prior stroke, TIA, or amarosis fugax, however the proportion is lower than institutional and clinical trials which likely have more accurate clinical assessments. Using the NIS, McPhee et al. found 92.1% of carotid procedures were performed for asymptomatic disease23
while Vogel et al. found a <3% symptomatic proportion using differing algorithm to define symptom status.21
Comparatively, Kang et al. reported a 43% symptomatic rate in nearly 4,000 patients from the National Surgical Quality Improvement Program from 2005-2006.25
However, results from early NSQIP data may not reflect what is occurring nationally.
The ARCHeR trial for high risk patients undergoing CAS showed a 30-day stroke or death rate of 11.6% for symptomatic patients and 5.4% for asymptomatic patients.26
This high event rate in symptomatic patients is similar to the national outcomes that we found in our analysis (14.4% in-hospital stroke or death). We found also, however, that non-high risk patients also had a high combined stroke and death rate at 11.8% whereas asymptomatic patients had significantly lower event rates (1.5% high risk, 1.8% non-high risk), showing that symptom status confers the greatest risk in patients undergoing carotid stenting. Symptomatic patients older than 80 years did particularly poorly with combined stroke and death rates of 14.7% after CAS and 6.7% after CEA. Careful patient selection should be employed when considering carotid procedures in this age group.
There was an increased likelihood of CAS patients to be symptomatic. This is likely attributable to CMS reimbursement requirements as well. Evaluation of patients pre- and post-operatively may be more accurate for CAS given that a detailed neurological evaluation is required by CMS. This may more accurately identify symptomatic patients preoperatively and may detect more minor strokes postoperatively. However, this should not impact the analysis of mortality. Adjustment for symptom status may in fact bias mortality evaluation in favor of stenting.
Our analysis showed that for patients undergoing concurrent carotid repair and CABG/Valve surgery, CAS did not have an increased risk of stroke or death compared to CEA. Concurrent CABG/Valve was performed in 3.9% of carotid revascularization procedures. It is unlikely that those patients undergoing concurrent carotid and cardiac surgery would have differing procedural risk patterns compared to those not undergoing cardiac surgery. CAS is typically performed in a separate setting prior to CABG therefore those dying after CAS would not be detected in this analysis. Additionally, patients with a major CVA after CAS are likely to have CABG deferred therefore there is inherent bias against CEA which may more commonly be performed in the same setting as CABG/Valve. The use of aspirin, plavix, and statins may be more likely in patients undergoing a CABG and blood pressure may be better optimized, however how this impacts CEA versus CAS differentially is unknown. While many publications regarding CEA and CABG exist, information specifically about combined CAS and CABG is scarce and mostly limited to single institution studies.5,16,28
Naylor et al recently systematically reviewed all published studies of staged CAS and CABG and found a 30-day stroke or death rate of 9.1% with an overall mortality of 5.5%.5
Another recent systematic review found a 30-day stroke and death rate of 12.3% and mortality of 7.6% for CAS and CABG.27
This is significantly higher than our current results of 3.2% stroke/death and 1.6% mortality for in-hospital CAS/CABG outcomes. Timaran et al. used the NIS from the years 2000-2004 (prior to CAS specific ICD-9 codes), spanning the time before the current study, to compare CAS and CABG to CEA and CABG. At that time only 3.3% (887) of combined cardiac and carotid procedures were CAS compared to 96.7% CEA. They found an in-hospital stroke and death rate after CAS and CABG of 6.9% and after CEA and CABG of 8.6% but no difference in predictive risk on multivariate analysis.28
Given the substantially higher rates of adverse events in this group of patients, it seems prudent to analyze their outcomes separately. Similarly, improved stratification of outcomes within other high risk subgroups appears warranted.
We adjusted outcomes based upon medical high risk criteria but not for anatomic high risk which is unattainable in the NIS data. Most of these have been shown to increase risk of local complications such as infection and nerve injury but not stroke or death.29,30
Failure to detect anatomic high risk as an indication for CAS is unlikely to affect these results. Contralateral occlusion has been shown to increase risk of CEA in large studies, but little data exists to evaluate the impact on CAS outcomes.31-32
Outcomes improved with time as shown in our multivariate analyses. This was true for the overall group as well as for CAS and CEA independently. With improving technology and increasing practitioner expertise, this is expected for CAS, however it was a surprising finding with CEA. This may indicate that as CAS becomes more widely used, fewer high risk patients are having CEA performed, thus improving the results of CEA over time.
We included PCI and diagnostic cardiac catheterizations in our study as coexisting cardiac procedures. There was a greater number of both performed during the same admission as CAS compared to CEA however, which may indicate that these catheter-based procedures are done prior to or with CAS while they may more likely reflect postoperative cardiac complications after CEA.
The limitations of this study are primarily due to the nature of the database as an administrative dataset some of which are noted above. Additionally, the database is limited to inpatient outcomes only, therefore we cannot identify staged carotid and cardiac procedures if a patient was discharged between procedures. We also cannot extend outcomes to 30-day results as much of the prior literature does limiting accurate comparison. Some stroke events occur after hospital discharge, so this is an important distinction.24
The dataset has no information on severity of stenosis or anatomic risk factors that may predispose a patient to adverse outcomes with either repair method. For preoperative data, we cannot determine severity of prior stroke, laterality, frequency of symptoms, or the temporal relationship of symptoms and surgical repair.