Clinical and Angiographic Risk Factors for Stroke and Death within 30 Days after Carotid Endarterectomy and Stent-Protected Angioplasty: a Subanalysis of the SPACE Study

Stingele R, Berger J, Alfke K, et al., SPACE Investigators.
Lancet Neurol 2008;7:216–22

Background: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors.

Methods: We analyzed data from 1196 patients randomized to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischemic or hemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028.

Findings: Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p = 0.001) but not in the CEA group (p = 0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups.

Interpretation: Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

Comment

Although SPACE has proven the noninferiority of CAS compared to CEA, the results at least lowered the enthusiasm that CAS will once replace CEA. It is difficult to compare composite stroke/death rates between different studies and complication rates are generally lower when reported by surgeons than by neurologists [1]. However, in SPACE both treatment modalities had ipsilateral stroke or death rates beyond the acceptable limits of the AHA/AHS [2, 3]. These associations recommend CEA if composite complication rates are lower than 3% in asymptomatic patients, lower than 5% in patients with transient ischemic atttack, and lower than 7% in patients with stroke as qualifying event, respectively. Latter event rates were 8.3% and 7.0% in the CAS and 6.6% and 8.3% in the CEA arm of SPACE.

Both, vascular surgeons and neuroradiologists attempt to make their treatments safer. While vascular surgeons have done so for many years, neuroradiologists are still at the beginning. This analysis of SPACE subgroups is one step among many steps that still have to be done. It convincingly shows that in the CAS arm younger patients have distinctly lower stroke and death complications than older patients. By contrast, in the CEA arm complication rates are equal in all age groups. Other modifying factors like stent design, size of the cell-free area [4], use of protection devices, etc. are currently investigated and will hopefully help to make stent-protected angioplasty more beneficial.

References

1. Rothwell PM, Slattery J, Warlow CP. A systematic review of the risks of stroke and death due to endarterectomy for symptomatic carotid stenosis. Stroke 1996;27:260–5.
2. Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy. Circulation 1998;97:501–9.
3. Goldstein LB, Adams R, Alberts MJ, et al. Stroke 2006;37:1583–633.
4. Bosiers M, de Doanto G, Deloose K, et al. Does free cell area influence the outcome in carotid artery stenting? Eur J Vasc Endovasc Surg 2007;33:135–41.

(Submitted May 26, 2008)

Horst Urbach, Bonn, Germany