Let's Talk: Journal Club

Article used: Ferguson, Gary G., et al. "The North American symptomatic carotid endarterectomy trial: surgical results in 1415 patients." Stroke 30.9 (1999): 1751-1758.

DOI: https://doi.org/10.1161/01.STR.30.9.1751

Journal club (for those familiar, and also for those who may not be) is meant to serve as a place for physicians to discuss recent, relevant and important research and the clinical implications it carries.

Now, this paper is not recent, but it is both relevant and important, and carries significant clinical applications.

So what exactly are we discussing? The NASCET trial (The North American Symptomatic Carotid Endarterectomy Trial) was first published in 1999, and enrolled a cohort of 1415 patients.

It aimed to ascertain the incidence of peri-operative stroke/death at 30 days and then 90 days post carotid endarterectomy (CE) (which we'll discuss a bit later on). We'll assess the research question (posited above- the surgical complications post endarterectomy), the methodology and the outcomes (and conclusions drawn) for clinical practice.

Inclusion criteria were as follows: hemispheric transient ischemic attack (TIA), transient monocular blindness, or a nondisabling stroke associated with a stenosis of 30% to 99% in the ipsilateral carotid artery based on linear diameter reduction, and patients who could not give consent or had no pertinent angiographic studies were excluded. Additional exclusion criteria were an intracranial lesion that was more significant than the proximal carotid lesion, were unlikely to survive 5 years because of intercurrent disease, had disabling stroke (Modified Rankin score ≥3), or had symptoms likely attributable to other disease or a prior ipsilateral CE.

Strokes, as outcome events, were classified as disabling or nondisabling at 30 days postoperatively (perioperative stroke rate) and at 3 months, the time of the final assessment of stroke severity in each case, with the use of Modified Rankin disability scores.

Altogether, 1453 patients were randomized to the surgical arm of the study: In total, there were 92 perioperative outcome events, for an overall rate of 6.5%. At 30 days, 15 patients had died (1.1%), equally divided between nonstroke deaths and stroke deaths, and 25 patients had suffered a disabling stroke (1.8%), giving a perioperative rate of disabling stroke and death of 2.9%. There was no statistically significant difference in the rate of disabling stroke and death at 30 days between the moderate stenosis (2.8%) and severe stenosis (3.0%) groups. Between 30 and 90 days, 1 patient with a disabling stroke died, while 8 patients with moderate stenosis and 3 patients with severe stenosis had an improvement in stroke severity from disabling to nondisabling. Thus, at 90 days, 1.1% of the surgical patients with a perioperative outcome had died, while 0.9% had a persisting, disabling stroke, giving an overall rate of persisting, disabling stroke and death in the surgical group of 2.0%. The rate of nondisabling stroke at 90 days was 4.5%.

Risk Factors for 30 day perioperative complications

Kaplan Meier curves for survivability post CE

Importantly: The European Carotid Surgery Trial (ECST), similar in size to NASCET, has reported results with comparable rates of perioperative rates of stroke and death.5 In 1745 patients, the death rate at 30 days was 1.0%, the disabling stroke rate 2.5%, and the nondisabling stroke rate 3.5%, for an overall rate of 7.0%. Comparison of the surgical results from these trials to large case series and community surveys is inappropriate, since such reports include nonrandomized patient selection and lack independent verification and evaluation of perioperative outcome events. In severe, symptomatic carotid stenosis (≥70%), the benefit from CE is very significant and increases dramatically as the stenosis increases up to 95%. In patients with high-moderate stenosis (50% to 69%), the benefit from CE is modest. Benefit will only be achieved in the latter group if there is a maximum disabling stroke and death rate of 2% coupled with selection of patients at highest risk.

Ultimately they concluded: The overall rate of perioperative stroke and death was 6.5%, but the rate of permanently disabling stroke and death was only 2.0%. Other surgical complications were rarely clinically important. Carotid endarterectomy is a durable procedure.

So what did we learn from this trial?

We learnt of the incidence (and nature) of peri-operative complications from CE, and we learnt that in patients with >70%, symptomatic carotid artery stenosis, CE (the surgical procedure to remove plaque within the carotid artery) does have benefit, and can be well tolerated. However, given that strokes post operatively can be debilitating, one must carefully weigh risks vs benefits before advocating for CE.