As a 4th year medical student I rotated on the vascular surgery service at a local hospital. One of the vascular surgeons loved music (all music!) and would quiz me on the musicians as each song came on. I usually got them wrong and longed for him to just ask me an anatomy question instead so I could finally get something right. When it came to performing a carotid endarterectomy, however, he only played classical music, his “carotid playlist”. He wanted full concentration and focus for this delicate operation, one that carried a very real risk of myocardial infarction (MI) and/or stroke.
As we evolve in medicine, we are constantly looking for new ways to improve care and minimize risk to patients. This is especially evident in the field of surgery. Over the past 40 years, the practice of surgery has changed significantly, shifting away from big, open operations to minimally invasive operations with lower morbidity. Current surgical residents may never even see an open appendectomy — I have only seen one!
In an effort to minimize the risk associated with carotid endarterectomy, carotid artery stenting was developed as a minimally invasive technique for higher risk patients (due to anatomical difficulties such as prior irradiation or significant medical comorbidities). The first major trial comparing carotid endarterectomy to stenting was the CREST trial by Brott et al. published in 2010 in NEJM. In this week’s issue of NEJM, Brott et al. now report the results after 10 years follow-up.
This trial enrolled 2502 symptomatic and asymptomatic patients with carotid stenosis and randomly assigned them to endarterectomy or stenting with embolic protection (a device that captures and removes emboli). All patients undergoing stenting received dual-antiplatelet therapy while those undergoing endarterectomy received aspirin. Both groups of patents also received the standard of care medical therapy at the time. The primary composite endpoint was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke at the designated follow-up period.
The 2010 publication had 4 years of follow-up and found that while there was a higher periprocedural risk of stroke in the stenting group (4.1% vs. 2.3%, P=0.01) and MI in the endarterectomy group (1.1% vs. 2.3%, P=0.03), there was no significant difference in the primary composite outcome between the two groups at 4 years (7.2% for stenting and 6.8%, for endarterectomy). Now, after 6 more years of follow-up (10 total), there remains no significant difference in the rate of primary composite end point between stenting and endarterectomy (11.8% vs. 9.9%). This remained true when stratified by symptomatic status. There was a significant different in rate of death or ipsilateral stroke at 10 years (11% for vs 7.9% for endarterectomy, p=0.04), however, this was attributed to the higher rate of periprocedural stroke with stenting.
ACT-I, a similar trial comparing endarterectomy to stenting by Rosenfield et al. was also published in this week’s NEJM. This trial, however, only enrolled patients who were asymptomatic. As in CREST, patients received dual anti-platelet therapy in the stenting group, aspirin in the endarterectomy group, and current standard medical therapy. This study was designed as a non-inferiority study and used a primary composite end point of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year. There was no difference in primary composite end point at 1 year (event rate, 3.8% and 3.4%, respectively; P=0.01 for noninferiority). While there was numerically a higher rate of stroke in the stenting group within 30 days of procedure, it did not reach statistical significance (2.9 vs 1.7% p=0.33), in contrast to CREST. At 5-year follow-up, rate of freedom from ipsilateral stroke and overall survival rates did not differ.
What do the results of these two studies tell us? Should all asymptomatic carotid stenosis patients undergo carotid stenting? How do we put this into practice? The accompanying editorial by Spence and Naylor sheds some light on these questions, remarking that the results of these two studies “should dispel any lingering concerns about the durability of stenting. That issue has now surely been resolved.” What has not been resolved, though, is the generalizability of these two studies and how to manage an asymptomatic carotid stenosis patient. To this end they comment, “No one should harbor any illusions that ACT I and CREST have resolved the latter [asymptomatic management] issue.”
Two major limitations vex both of these studies. First, they were both conducted at centers of excellence with the best surgeons and interventionalists performing the procedures. In places where this is not available, periprocedural stroke rates may be higher and thus the risk of intervening may outweigh the benefits. Second, neither study compared stenting and endarterectomy to optimal medical treatment only. Medical treatment for prevention of stroke has greatly improved over the past 20 years and this needs to be taken into account when interpreting these studies. Spence and Naylor conclude, “Outside clinical trials, endarterectomy and stenting should be reserved for patients with symptomatic severe stenosis or for asymptomatic patients who are shown to be at higher risk for stroke with medical therapy than with intervention.”
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Andrea Merrill, MD
Andrea was a 2015-2016 NEJM Group Editorial Fellow. She is currently in the middle of her General Surgery residency at Massachusetts General Hospital and is also conducting research focusing on improvements in breast cancer surgery. She plans to pursue a fellowship in Surgical Oncology at the completion of her residency.