The trial (EVA-3S) was stopped early, after the inclusion of 527 patients, for reasons of both safety and futility. The 30-day risk of any stroke or death was significantly higher after stenting (9.6%) than after endarterectomy (3.9%), resulting in a relative risk of 2.5 (95% CI, 1.2 to 5.1). The 30-day incidence of disabling stroke or death was 1.5% after endarterectomy (95% CI, 0.5 to 4.2) and 3.4% after stenting (95% CI, 1.7 to 6.7); the relative risk was 2.2 (95% CI, 0.7 to 7.2). At six months, the incidence of any stroke or death was 6.1% after endarterectomy and 11.7% after stenting (P=0.02). Cranial nerve injury was more common after endarterectomy than after stenting.
The practice of interventional physicians has expanded in the last few years to include placement of stents—not only in coronary arteries but also in carotid arteries and other vessels. As hospitalists, we must be aware of the latest research in this changing field to provide the best evidence-based advice to our patients.
Currently, the only use of carotid stenting that has been approved by the Food and Drug Administration (FDA) is in symptomatic patients with carotid artery stenosis of 70% or more who are at high surgical risk. This FDA approval is based on the results of the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) study, which included symptomatic patients with carotid artery stenosis exceeding 50% and asymptomatic patients, with stenosis exceeding 80%, who were at high surgical risk mainly due to severe coronary artery disease. The SAPPHIRE study showed that stenting was safer than endarterectomy mainly due to lower risk of myocardial infarction within 30 days after carotid stenting as compared with surgery. There was no significant difference in the rates of stroke or death between stenting and endarterectomy.
Why does the EVA-3S trial reported in NEJM show opposing results? The patients in the trial were different than the ones included in the SAPPHIRE study, and the periprocedural protocol was less strict. The patients in the EVA-3S trial were not at high surgical risk. Further, all patients in the EVA-3S trial had symptomatic carotid artery stenosis, whereas the majority of patients in the SAPPHIRE study were asymptomatic. Use of aspirin and clopidogrel or ticlopidine three days before carotid-artery stenting was only recommended in the EVA-3S trial but was required in the SAPPHIRE trial.
The ongoing Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), funded by the National Institutes of Health, is enrolling patients with an average surgical risk similar to those in the EVA-3S study. The CREST study, which is expected to enroll 2,500 patients, may be able to provide a more definitive answer regarding the best treatment for symptomatic patients with high-grade carotid stenosis with an average surgical risk.
In the meantime, what should we recommend to our patients? For symptomatic patients with carotid artery stenosis of 70% or more, endarterectomy is superior to medical therapy alone. For asymptomatic patients with carotid artery stenosis exceeding 60%, endarterectomy is also superior to medical therapy alone, assuming a risk of perioperative stroke or death of less than 3%. Currently, the only accepted indication for stenting is in symptomatic patients with carotid artery stenosis exceeding 70% and a high surgical risk.
D-Dimer Testing to Risk Stratify VTE Patients
Palareti G, Cosmi B, Legnani C, et al. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med. 2006;355:1780-1789.
D-dimer levels have been used to assist in diagnosing initial episodes of venous thromboembolism (VTE). Although not specific, D-dimer testing is very sensitive for VTE, giving it a high negative predictive value. Further, duplex ultrasound often remains abnormal after VTE, making the distinction between recurrent disease and old disease problematic when symptoms recur.