Stroke after carotid stenting and endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

Abstract

Background: Stroke occurs more commonly after carotid artery stenting than after carotid endarterectomy. Details regarding stroke type, severity, and characteristics have not been reported previously. We describe the strokes that have occurred in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).

Methods and results: CREST is a randomized, open-allocation, controlled trial with blinded end-point adjudication. Stroke was a component of the primary composite outcome. Patients who received their assigned treatment within 30 days of randomization were included. Stroke was adjudicated by a panel of board-certified vascular neurologists with secondary central review of clinically obtained brain images. Stroke type, laterality, timing, and outcome were reported. A periprocedural stroke occurred among 81 of the 2502 patients randomized and among 69 of the 2272 in the present analysis. Strokes were predominantly minor (81%, n=56), ischemic (90%, n=62), in the anterior circulation (94%, n=65), and ipsilateral to the treated artery (88%, n=61). There were 7 hemorrhages, which occurred 3 to 21 days after the procedure, and 5 were fatal. Major stroke occurred in 13 (0.6%) of the 2272 patients. The estimated 4-year mortality after stroke was 21.1% compared with 11.6% for those without stroke. The adjusted risk of death at 4 years was higher after periprocedural stroke (hazard ratio, 2.78; 95% confidence interval, 1.63-4.76).

Conclusions: Stroke, particularly severe stroke, was uncommon after carotid intervention in CREST, but stroke was associated with significant morbidity and was independently associated with a nearly 3-fold increased future mortality. The delayed timing of major and hemorrhagic stroke after revascularization suggests that these strokes may be preventable.

Trial registration: ClinicalTrials.gov NCT00004732.

Figure 1

Box-and-whisker plots showing the distribution of NIHSS following periprocedural stroke for CEA (red) and CAS (blue) patients. The horizontal axis shows the time period, and provides the number of patients in the CEA and CAS treatment group respectively (i.e. n = 21/48 implies 21 patients in the CEA group and 48 in the CAS group). The bottom of the box is the 25^th percentile, the line in the center the 50^th percentile (median), the top of the box the 75^th percentile, and the top of the whisker the 90^th percentile. In the cases where the median is not shown, it is equal to zero (0) and is plotted with the 25^th percentile (also zero). Data points outside the 90^th percentile are shown as dots. Because there is no NIHSS score for patients who have died, these patients are shown in the gray shaded box at the top of the figure (representing an outcome that is worse than any patient surviving). Note that this display shows the entire distribution of the NIHSS outcomes as a function of time, allowing the reader to see that those patients alive at the PostProc period are doing worse than the patients alive at “1 Mth” (note the lower median and 75^th percentiles); however, at “1 Mth” there were deaths and a small proportion of patients with a very poor outcome. PreProc=Pre-procedure, PostProc=Post-procedure, Mth=Month, and n=number.

Figure 2

Timing of stroke after carotid revascularization.

Figure 3

Ischemic stroke patterns. Representative ischemic stroke cases. First row, 3 patients with scattered emboli in the distribution of the revascularized artery. Second row, 3 patients with cortical infarction in the territory of the revascularized artery. Third row, 4 patients with subcortical infarction.

Figure 4

Mortality after periprocedural stroke (intention-to-treat analysis). Survival curve of mortality by stroke (n=81) or nonstroke (n=2421) status. This analysis includes all 69 periprocedural strokes, 3 strokes that occurred after randomization but before the procedure, and 9 strokes that occurred after the 30-day periprocedural period. Log-rank test P<0.0001. Estimated mortality rate at 4 years was 11.6% (±1.0; 162/2421) in the stroke-free group and 21.2% (±5.2, 15/81) in the stroke group.