Timing and Selection of Patients for Carotid Revascularization

Of all strokes, one fifth can be attributed to significant stenosis of the internal carotid artery
(ICA). In patients with significant ICA stenosis, both carotid endarterectomy (CEA) and
carotid artery stenting (CAS) are used to prevent strokes and stroke-related mortality.
However, carotid surgery itself imposes an operative risk, which directly limits the intended
benefit of carotid revascularization. This is especially important for asymptomatic patients,
in whom the absolute stroke risk reduction heavily depends on a low operative risks.
Hence, patient selection is vital, as a high operative risk will diminish the preventative effect
of carotid revascularization. In part I of this thesis we discuss global differences in patient
selection for carotid revascularization in chapter 1 and key differences among symptomatic
patients in chapter 2.
Part II of this thesis focusses on specific patient characteristics and operative factors
that might result in a higher operative risk of stroke or death after carotid revascularization.
This is important, as understanding the impact of these factors may aid the selection of
patients for carotid surgery. For instance, both anemia and insulin-dependent diabetes
mellitus (DM) are associated with an increased risk of stroke or death after surgery in
general. However, their relation to outcomes after CEA is less well described. Hence, in
chapter 3 we evaluate the associated risk of anemia on outcomes after CEA and in chapter
4 we evaluate the impact of DM and insulin use. In addition, despite ongoing efforts, racial
disparities in patients undergoing CEA remain, as, in the United States of America, eligible
Black patients are less likely to undergo CEA and have a higher disease burden. However,
the impact of race on outcomes after CEA is conflicting. Therefore, we evaluate the
impact of race on early and long-term outcomes after CEA in chapter 5. While, in chapter
6, we compare factors associated with intraoperative and postoperative strokes between
patients undergoing CEA and CAS. Moreover, based on the results from the SAPPHIRE
and CREST trials, the 14-societis guidelines document on carotid surgery listed a number
of ‘high-risk’ criteria, which would result in an unwarranted high operative risk after CEA,
hence CAS may be the preferred treatment option. Contralateral carotid occlusion is used
as one of these criteria to recommend CAS over CEA. However, the use of CCO as a ’highrisk’
criterion for complications after CEA has been disputed, as outcomes after CEA in
patients with CCO differ greatly between studies,13–15 Thus, in chapter 7, we assess
outcomes after CEA in patients with CCO, to see if indeed their stroke/death rates are
above the guidelines threshold of 3% for asymptomatic and 6% for symptomatic patients.
Moreover, as evidence supporting the hypothesis that patients with CCO experience lower
stroke/death rates after CAS than after CEA is lacking. We discuss our ongoing study,
comparing outcomes among patients with CCO between CEA and CAS, using the pooled
data from the EVA-3S, CREST, SPACE, and ICSS randomized clinical trials in chapter 8.
Besides the challenges in patient selection, choosing the optimal timing of carotid
revascularization after the index stroke in symptomatic patients remains a topic of debate,
which we discuss in part III of this thesis.16 Although the reported high pre-operative stroke
recurrence risks prompted a need for early revascularization, recent studies demonstrated
that early revascularization was associated with a higher operative risk. Unfortunately,
high quality data is lacking, thus we evaluate the differences between early and late
revascularization after the index stroke in perioperative outcomes between CEA and CAS
in chapter 9. While we assess the optimal timing for CEA in symptomatic patients in chapter
10.