CREST Analysis: Stroke Uncommon After Carotid Procedures, May Be Preventable

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Key Points:
  • Strokes rare after carotid revascularization, but carry serious consequences
  • Major or minor stroke almost triples mortality risk at 4 years
  • Delay in major strokes suggest they may be prevented with better BP control

By Jason Kahn
Thursday, November 29, 2012

Periprocedural strokes are rare in patients undergoing carotid revascularization, occurring at a rate of 3.0%, with less than 1.0% suffering major strokes, according to a subanalysis of the CREST trial published online November 16, 2012, ahead of print in Circulation. Moreover, the delayed timing of severe strokes suggests they may be preventable.

The main Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) randomized 2,502 patients with symptomatic or asymptomatic carotid stenosis to CEA or CAS. Overall, there was no difference between the 2 groups in the estimated 4-year rates of the primary endpoint (composite of periprocedural stroke, MI, or death, or the incidence of ipsilateral stroke ≤ 4 years). However, stenting carried a higher risk of stroke and surgery a higher risk of MI.

In the subanalysis, researchers led by Thomas G. Brott, MD, of the Mayo Clinic (Jacksonville, FL), looked at strokes that occurred among the 2,272 patients who received their assigned treatment within 30 days of randomization. The stroke rate within 30 days of the procedure was 3.0% (n = 69), with a major stroke rate of 0.6% (n = 13), meaning that the majority of strokes (81%) were minor.

Minor Strokes Immediate, Major Ones Delayed

Strokes were also overwhelmingly ischemic (90%), located in the anterior circulation (94%), and ipsilateral to the treated artery (88%). The median time to minor stroke was 0 days, with a median time of 3 days to major stroke.

Strokes were disabling (modified Rankin Scale score > 2 at 30 days) in almost one quarter of patients (23.4%), while mortality among patients with stroke was 14.5% at 1 year. There were 7 intracerebral hemorrhages, 5 of them resulting in death.

There was little evidence of differences in the severity of strokes between the CEA and CAS groups (P > 0.27), and the chance of death following periprocedural stroke was similar for patients in each treatment groupat 1 month, 6 months, and 12 months.

Therefore, the authors noted, while there were more than twice as many strokes among CAS patients as CEA patients (48 vs. 21), the distribution of severity did not seem to differ by treatment strategy.

Regardless of Severity, Stroke Increases Mortality Risk

In a separate intention-to-treat analysis, the estimated 4-year mortality rate in non-stroke patients was 11.6% compared with 21.2% in those who suffered any stroke (adjusted HR 2.78; 95% CI 1.63-4.76). This relative increase is comparable, the researchers note, to the magnitude of the increase in mortality risk among CREST patients who suffered a perioperative MI (HR 3.67; 95% CI 1.71-7.90).

“Overall, stroke, particularly severe stroke, was uncommon after carotid intervention in the CREST trial but was associated with significant morbidity and mortality,” the study authors conclude. “The timing of major stroke after revascularization suggests that major stroke is potentially preventable. Minor stroke occurred most commonly and temporally at the time of CAS suggesting that CAS has potential for further improvement from expected advances in technology, technique, and training.”

According to Christopher J. White, MD, of the Ochsner Heart and Vascular Institute (New Orleans, LA), the encouraging news from the subanalysis is that the frequency of strokes is quite low. “In relative terms, this is not a big frequency issue, but when it happens, it’s important, and the paper makes it clear you cannot ignore minor strokes,” he told TCTMD in a telephone interview. “They have consequences, just as minor MIs have consequences.”

Avoiding a Blowout

He also agreed with the authors that there are implications for prevention. “What they suggest is it’s a hyperperfusion syndrome,” Dr. White said. “You open the artery with stenting or surgery and you get a blowout 3 or 4 days later from high blood pressure. They’re suggesting that blood pressure is not being carefully enough controlled and with better titration of meds, we might prevent these [strokes].”

In addition to “stringent blood pressure control,” the authors suggest “[u]nerring use of antiplatelet medication, statins, and good diabetic management” in order to reduce the risk of major ischemic stroke after carotid revascularization.

Another potential way to prevent strokes in such patients, Dr. White noted, may be with newer cerebral protection devices. “Proximal protection devices are better than filters in terms of [catching] the debris that gets through,” he said. “A lot of us think that one of the great ways to prevent small and minor strokes in carotid stenting patients is by more widespread use of proximal protection, which is probably more effective than what was done in the CREST trial.”

Overall, Dr. White added, the “less filling, tastes great” debate between interventionalists and surgeons over complications after carotid revascularization should cease. “The interventionalists point to more MIs with surgery, and the surgeons point to more strokes with stenting,” he said. “What we really need to be doing is trying to avoid both of these. There’s nothing good about MIs or strokes.”


Hill MD, Brooks W, Mackey A, et al. Stroke after carotid stenting and endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Circulation. 2012;Epub ahead of print.



  • The study was supported by the National Institute of Neurological Disorders and Stroke and supplemental funding from Abbott Vascular Solutions.
  • Dr. Brott reports no relevant conflicts of interest.
  • Dr. White reports serving as a principal investigator for a carotid stenting trial (CABANA), and as steering committee chair for the NCDR CARE registry.


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