In the base case analysis, CEA was the dominant option for the treatment of symptomatic carotid stenosis in a hypothetical cohort suitable for either CEA or CAS. CEA maximizes health benefits and cost savings. Deterministic sensitivity analyses showed that the assumptions regarding long-term stroke rates and mortality influence the suitability of CEA as the cost-effective option. With lower thresholds for cost-effectiveness, the probability that CEA is treatment of choice increases from 59% to 68%.
The recent follow-up data from EVA-3S, SPACE and SAPPHIRE fail to demonstrate a detectable difference in the annual rates of stroke or death. None of these studies shows non-inferiority on a yearly time scale. This analysis incorporated weighted averages (by trial size) for stroke or death beyond 30 days. These weighted averages do show a higher long-term risk following CAS. Aspects of clinical uncertainty surrounding the long-term performance of CEA and CAS are addressed by the probabilistic sensitivity analysis which randomly samples long-term probabilities.
To our knowledge, this is the first cost-effective analysis of CEA and CAS in symptomatic subjects incorporating meta-analyses for 30-day peri-procedural events along with weighted estimates of long-term events (6
). Although the meta-analysis used for the base case analysis included both those at high risk and standard risk for CEA, a majority of the subjects represented a standard risk cohort. Surgical risk must be considered when applying these cost-effectiveness findings to a general population. Thus, if long-term stroke rates following CEA in high risk individuals are greatly increased, CAS may be an acceptable alternative.
MI was included as a health state in the model because it poses a major public health burden. If 30-day major and minor stroke risks are comparable, differences in the 30-day likelihood of MI could potentially make one procedure preferable over the other. However, our cost-effectiveness model is robust to a wide range of 30-day probabilities of MI.
The identification of death and major stroke rates as contributing factors to the cost-effectiveness analysis in our model is consistent with a previous study (13
). Advantages to our model include incorporating outcomes from a meta-analysis with MI, major stroke and minor stroke as adverse events, the use of nationally based cost data, and consideration of both 30-day per-procedural and long-term events.
There are several limitations to this analysis. This study is a secondary data analysis that considers event probabilities for the base case analysis in a symptomatic cohort. Revascularization for asymptomatic subjects should have lower 30-day rates of adverse events which may limit the generalization of these results to an asymptomatic population. Follow-up in our model is limited to a timeframe of 2 to 4 years (6
). Finally, the current model only considered major outcomes including death, major stroke, minor stroke and peri-procedural MI.
SPACE reported greater restenosis following CAS at 2 years, though restenosis rates following CAS may be artificially high (6
). Residual stenosis after CAS may be subject to overestimation if traditional ultrasound criteria are used (3
). Also, there is no consensus for the treatment of post-CAS restenosis (16
). Because of the possibility of overestimation and no data regarding defined treatment, restenosis was not included in our model, per se, unless it led to an event. Therefore, including restenosis as a health state would not change the results of our analysis. Treatment for restenosis, however, could increase CAS-associated costs relative to the costs of CEA. This increased CAS cost would not change the base case conclusions from cost-effectiveness analysis; CEA would still remain the least costly option and produce the most QALYs.
Although considerable uncertainty exists in the lifetime cost-effectiveness of CAS compared with CEA, our estimates suggest with nearly 60% probability that CAS may not be a cost-effective alternative. Given the uncertainty about the effectiveness and cost-effectiveness of CAS compared to CEA, CAS should remain limited to randomized trials or select populations of patients with carotid stenosis. Such trials will clarify the risks and benefits of CAS. This model provides a framework for the interpretation of ongoing trials that highlight the long-term benefits of carotid artery revascularization for secondary prevention of stroke.