High periprocedural and long-term mortality among Medicare patients who undergo carotid artery stenting (CAS) suggests that the benefits of the treatment seen in randomized controlled trials may not apply to the wider population, according to a large retrospective study published online January 12, 2015, ahead of print in JAMA Neurology. This disconnect may be especially true for patients who are older and carry a high burden of comorbidities.

“These findings raise questions about whether performing CAS is justified if periprocedural risks are too high or if patients do not live long enough to benefit from the main advantage of CAS, which is stroke prevention,” the authors say.

Soko Setoguchi, MD, DrPH, of the Duke Clinical Research Institute (Durham, NC), and colleagues analyzed data on 22,516 Medicare patients (mean age 76.3; 60.5% male; 93.8% white) from the Centers for Medicare & Medicaid Services (CMS) database who underwent CAS with embolic protection between 2005 and 2009.

About half of patients were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis of at least 70%. Overall, patients had a high burden of comorbidities, including ischemic heart disease, heart failure, diabetes, and PAD, and almost one-quarter had undergone CABG during the previous year. In addition, 27.8% were admitted nonelectively for CAS.

The mean numbers of procedures performed over the previous year were 13.9 for the 1,995 operators and 29.8 for the 749 hospitals.

Periprocedural Complications, Competing Risks Elevated

Risks of mortality and stroke or TIA were high, both periprocedurally (within 30 days) and at a mean follow-up of 2 years (table 1). 

Periprocedural mortality and stroke/TIA risks were highest for patients who were:

• Symptomatic
• At least 80 years old
• Treated nonelectively with CAS
• At high surgical risk with symptomatic stenosis of at least 50%

Over follow-up, mortality risk exceeded one-third for patients who were:

• Aged 80 years or older
• Symptomatic
• At high surgical risk with symptomatic carotid stenosis of at least 50%
• Admitted nonelectively

Among asymptomatic patients, mortality after the periprocedural period exceeded one-third only among those at least 80 years old. Among symptomatic patients, all except those younger than age 75 had mortality risks exceeding one-third. In the latter subset, patients at least 80 years old and those admitted nonelectively experienced the highest risks at 46.0% and 40.4%, respectively.

Evidence of Medicare/Randomized Trial Disconnect

Almost 80% of the Medicare patients met the SAPPHIRE trial requirement of symptomatic stenosis of at least 50% or asymptomatic stenosis of at least 80%. Approximately half met at least 1 of SAPPHIRE’s high surgical risk criteria—mainly age over 80 and clinically significant cardiac comorbidities.

On the other hand, about 80% of Medicare patients were treated by physicians who did not meet the SAPPHIRE requirements of low periprocedural complication rates and a minimum number of procedures performed. Compared with the overall cohort, SAPPHIRE-like patients had slightly lower risks of periprocedural mortality or stroke/TIA as well as of stroke/TIA beyond the periprocedural period. Furthermore, only 15.5% of patients underwent CAS at centers similar to those in the CREST trial and only 9.3% were treated by physicians meeting the CREST proficiency requirements.

In an accompanying editorial, Mark J. Alberts, MD, of the University of Texas Southwestern Medical Center (Dallas, TX), observes that the 2-year mortality rate in the current study is considerably higher than that for almost any type of ischemic stroke. “This would obviously negate most, if not all, of the benefits of carotid stenting in at least one-third of treated patients,” he writes. More broadly, the study shows that “treating an artery may not treat the patient—at least not enough to keep him or her alive for more than a few years,” he says.

The high mortality seen in the CMS cohort can probably be explained by “a combination of advanced age and poorly controlled CVD risk factors as well as the inclusion of a sicker group of patients,” Dr. Alberts acknowledges, adding that data on the cause of death—not included in the analysis—could have shed more light.

Might CAS Be More Dangerous in the Elderly?

“However, we should be open to other possibilities,” Dr. Alberts cautions. Stenting a large vessel like the carotid may trigger release of adverse factors that lead to higher rates of CVD events, including death. In fact, that hypothesis is supported by recent studies linking inflammatory biomarkers to higher 5-year mortality in these patients, he adds.

“Perhaps the stenting itself further elevated some markers in a reactive manner, or perhaps those with higher levels of inflammation have worse symptoms,” Dr. Alberts suggests. “These issues deserve further study and may help guide patient selection and treatment.”

According to the authors, the findings also underscore the need to understand the benefits of CAS outside of randomized controlled trials “because few Medicare beneficiaries undergoing CAS… were treated by providers with proficiency levels similar to those of physicians in the SAPPHIRE trial or CREST.” Moreover, they point out, many patients were already at increased mortality risk due older age, symptomatic status, or nonelective indication.

In the end, Dr. Setoguchi and colleagues say, “[t]he decision to perform CAS should be based on overall survival as well as on the risk of complications and their effect on quality of life. The higher risk of periprocedural complications and comorbidity burden must be carefully considered when deciding between carotid stenosis treatments for Medicare beneficiaries. 

“Real-world observational studies comparing CAS, carotid endarterectomy, and medical management are needed to determine the performance of carotid stenosis treatment options for Medicare beneficiaries,” they add.

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Sources:
1. Jalbert JJ, Nguyen LL, Gerhard-Herman MD, et al. Outcomes after carotid stenting in Medicare beneficiaries, 2005 to 2009. JAMA Neurol. 2015;Epub ahead of print.

2. Alberts MJ. Carotid stenting—why treating an artery may not treat the patient [editorial]. JAMA Neurol. 2015;Epub ahead of print.

Disclosures:

• The study was funded by the Agency for Healthcare Research and Quality and the Centers for Medicare and Medicaid Services, both of the US Department of Health and Human Services.
• Dr. Setoguchi reports receiving a research grant from Johnson & Johnson and consulting fees from Sanofi-Aventis.
• Dr. Alberts reports no relevant conflicts of interest.

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