Personalising treatment in patients with carotid disease

Abstract

Approximately 10-15% of all ischaemic strokes are caused by atherosclerotic stenosis of the carotid artery. Conventionally, carotid stenosis was treated by surgical removal of the atherosclerotic plaque (carotid endarterectomy). Since the introduction of carotid artery stenting as a less invasive treatment alternative almost 20 years ago, the choice of the optimal treatment for the individual patient with carotid stenosis has remained controversial. This PhD thesis consisted of three individual projects and aimed to enable personalised treatment decisions for individual patients with carotid disease and explore parameters specifically linked to the mechanisms of stroke occurring as a complication of both revascularisation procedures. The first project consisted of a systematic review and meta-analysis with the aim to compare short-term risks and long-term effects on stroke prevention between carotid stenting and endarterectomy in patients with symptomatic or asymptomatic carotid stenosis. To this end, we performed a systematic Cochrane Review of all published randomised trials comparing carotid stenting versus endarterectomy to obtain precise overall estimates of procedural risks and long-term stroke recurrence rates. We found that in patients with symptomatic carotid stenosis, stenting and endarterectomy are equally effective in preventing recurrent stroke in the long-term, while stenting is associated with a higher risk of procedure related stroke or death. In patients with asymptomatic carotid stenosis, there may be a small increase in the risk of procedure related stroke or death associated with stenting. However, more data from randomised trials are needed. Concerning the durability of carotid stenting in the long-term, only limited data are currently available for asymptomatic patients and the existing evidence does not yet allow any firm conclusions. The second project comprised the systematic assessment of the anatomy of all supra-aortic arteries and pre-defined stenosis characteristics in order to investigate the association between vascular anatomy and the occurrence of procedure-related cerebral ischaemia after carotid artery stenting or carotid endarterectomy in patients with symptomatic carotid stenosis. We identified complex vascular anatomy as an important predictor for cerebral ischaemia during stenting, but not during endarterectomy. The third and fourth projects consisted of an individual patient data meta-analysis of four randomised clinical trials comparing carotid artery stenting versus endarterectomy for treatment of symptomatic carotid stenosis. This work resulted in two separate manuscripts. Within the first, we investigated whether the temporal distribution of stroke or death occurring within 30 days of treatment differed between the two procedures. In the second, we investigated if the procedural risks associated with carotid stenting and carotid endarterectomy within the examined trials had decreased over time. Our analysis revealed that the excess occurrence of stroke or death associated with stenting is limited to the day of treatment. In our analysis of temporal trends in procedure related risks, we were able to show that carotid revascularisation procedures became safer over time within the examined trials. This decline in risk was particularly apparent for endarterectomy.