Medical Discussions

Background

• Carotid enderarterectomy has been found to be beneficial for individuals with severe carotid stenosis
  • The North American Symptomatic Carotid Endarterectomy Trial (NASCET) showed that for patients with severe carotid stenosis defined as a stenosis greater than 70 percent, the number needed to treat in order to save one life over a period of 2 years was six.
• Noninvasive methods of opening a carotid stenosis through stents have been previously studied, but have not been shown to benefit patients.
• This randomized controlled trial was conducted to study whether stenting is not inferior to endarterectomy with regard to the risks of the procedure and its long term efficacy.
• Enrollment began in 2000, but the safety committee recommended it be stopped in September 2005 

Methods

• The study was completed in 20 academic and 10 nonacademic centers in France
  • Each center was required to have one neurologist, one vascular surgeon, and one interventionalist in order to join.
• Inclusion criteria
• • at least 18 years of age or older
  • had a hemispheric or retinal transient ischemic attack or a nondisabling stroke (or retinal infarct) within 120 days of enrollment
  • Stenosis of 60 to 99 percent in the sympotmatic  carotid artery as determined by the NASCET method
    • This was changed in October 2003 because endarterectomy was shown to benefit symptomatic patients with moderate stenosis
    • Stenosis was determined by catheter aniography or by both duplex ultrasound and MRA of the carotid artery
• Exclusion
  • Patinets were excluded if they moderate to severe diability from a stroke, nonathersclerotic carotid disease, severe tandem lesions, previous revascularization of a severe stenosis, h/o of bleeding d/o, uncontrlled HTN or DM, contraindications to heparin or clopidgrel, life expectancy  less than 2years, PCI or surgery within 30 days.
• Patients were randomized by the degree of stenosis defined as >90 or <90 percent.
• Primary endpt. was a composite of any stroke or death occuring within 30 days of treatment
• Secondary endpts.  were myocardial infarction, TIA, cranial nerve injury, major local complications and systemic complications within 30 days after treatment, and composites of any of the following – stroke or death within 30 days after treatment + any stroke from day 31 after treatment to the end of the followup.
• 872 patients needed to be enrolled to have a statistical power of 80 percent to assess whether stenting was not inferior to endarterectomy. 

Results

• 527 pts were ulitmately enrolled.
• There was no significant difference in the baseline characteristics of the two study arms.
• The study found that stenting carried a greater risk than did endarterectomy
  • 30 day incidence  of any stroke or death was 3.9 % (95% CI, 2 to 7.2) after endarterectomy  and 9.6% (95% CI, 6.4 to 14) after stenting, with an absolute risk increase of 5.7.
  • This means that an add’l stroke or death resulted when 17 patients underwent stented rather than endarterectomy.
  • 30 day incidence of disabling stroke or death was 1.5% (95% CI, o.5 to 4.2) after endarterectomy vs 3.4% (96% CI, 1.7 to 6.7)
  • A greater percentage of strokes occured on the day of the procedure in the stenting grp.
• The incidence of stroke or death did not vary based on whether the interventionalist was experienced or was being tutored during or after training
• Patients had stents placed with cerebral protection devices had a lower incidence of stroke, but endarterectomy was safer even after taking this into account.
• Hospital stay was shorter in the stenting group vs endarterectomy grp (3 days vs 4 days p 0.01)
• 30 day incidence of stroke or death in the stent group did not depend on whether patients were on antiplatelet therapy or not. 

Discussion

• The trial was stopped early for reasons of both safety and futility 
• In this study, the 30-day risk of stroke or death was significantly higher in the group that underwent carotid artery stenting.
• The differences are unlikely explained by the selection of sugeons with high level expertise and is most likely the a difference between the the therapeutic options.
• The differences persisted at 6 months, but long term follow up data has yet to be compiled

THE BOTTOM LINE – In patients with symptomatic carotid artery stenosis of 60 percent or more,  carotid artery stenting carries a higher risk of developing a stroke or dying at 30 days and 6 months when compared to carotid endarterectomy. 

In the comments section regarding this article…

Excellent review. I wanted to point out that the primary outcome for the study was long term mortality but that this data is actually buried within the text. The information you listed was from table 3 (which is presented as if it was the primary endpoint) but is actually the postoperative events at 30 days. The primary endpoint is actually 70 (22%) deaths in the revascularization group and 67 (23%) deaths in the no revascularization group at a median of 2.7 years (95% CI p=0.7-1.37). -Mike LoCurcio  

Thanks for the tip.  I’ll change the summary to reflect this.

to read the actual article click here

Background

• Patients with peripheral vascular disease (PVD) have a high prevalence of concomitant coronary artery disease (CAD), which leads to a high incidence of perioperative cardiac complications during vascular surgery.
• This is the first randomized trial to study the effect of coronary artery revascularization before elective vascular surgery
• Previous investigations into the topic have yielded mixed results
  • The cohort study, The Coronary Artery Surgery Study with peripheral vascular disease. followed patients for 3.5 years and showed improved outcomes in the group receiving revascularization as compared to the group receiving conservative therapy.
  • On the other hand, studies using large registries of patients have shown no benefit and potential harm patients by causing complications and delays of the needed vascular surgeries.
• The study was funded by the Cooperative Studies Program of the Department of Veteran Affairs Office of Research and Development.

Methods

• Inclusion criteria- patients scheduled for an elective vascular operation for either an expanded abdominal aortic aneurysm or severe symptoms associated with PVD in the legs.
• Exclusion criteria
  • Need for urgent or emergency surgery
  • Severe coexisting illness
  • Prior revascularization without evidence of recurrent ischemia
  • Left main stenosis 50 percent or greater
  • Left ventricle ejection fraction less than 20 percent
  • Severe aortic stenosis
• Coronary angiography was recommended if the consulting cardiologist deemed the patient at increased risk of perioperative cardiac complications.
  • Risk was determined by a combination of factors including the presence or absence of ischemia in noninvasive stress testing as well as independent risk factors of CAD, such as prior stroke, insulin-dependent diabetes, and renal failure.
• Based on the angiogram, patients received revascularization if the patients had a stenosis of at least 70 percent and could tolerate a revascularization procedure
  • The decision to undergo percutaneos coronary intervention (PCI) versus coronary artery bypass (CABG) was left up to the local investigators
• After randomization, either the cardiac or vascular procedure was expected to be performed within three weeks
  • Patients undergoing a CABG waited three months beore recieving their vascular procedure
  • Patients undergoing PCI waited two weeks for their vascular procedure to be completed due to increase risk of instent thrombosis
• Three days after vascular surgery was performed cardiac enzymes were monitored and ekgs were obtained.  Three months after vascular surgery, LVEF was determined using radionuclide angiography.
• Primary end point: long term mortality
• Secondary end point: myocardial infarction, stroke, limb loss, and dialysis.
• Patients were followed for approximately five years and the study was powered to detect difference in the 3.5 year survival rate of at least 75 percent of the two arms of the study.
• This was an intention to treat analysis

Results

• 5859 patients were initally screened and of these, 510 patients were eventually enrolled
  • Of the 510 patients who underwent randomization, 258 were assigned to a strategy of preoperative coronary artery revascularization and 252 underwent no preoperative revascularization.
• No significant differences in the baseline characteristics.
• Of the 258 in the coronary artery revascularization arm, 240 (93 percent) actually underwent revascularization
  • 41 percent underwent CABG
  • 59 percent underwent PCI
  • Patients undergoing had a higher number of vessels revascularized (3 vs 1.3), higher death rates (2 vs 1.4), and longer stays in the hospital (7 vs 1 day)
  • 87 percent of the patients eventually underwent vascular surgery
    • Vascular surgery occured  a median 48 days after CABG and median 41 days after PCI
• Before vascular surgery, there were more deaths in the coronary-artery revascularization group  than the conservatively managed patients ( 10 deaths vs 1 death)
• There was no mention in the stude regarding the number of perioperative myocardial infarctions during vascular surgery.
• Primary endpt –> at a median of 2.7 years after randomization, mortality was 22 percent in the revascularization grp and 23 percent in the no revascularization grp (relative risk, 0.98; 95 percent CI, 0.70 to 1.37)
• At thirty days, there was not a significant difference in death rates in the two groups (3.1 vs 3.4 percent, p=0.87)
• Secondary endpt –> there was also not a significant difference between the coronary artery revascularization arm versus the conservative management arm in terms of the 
  • the rate of myocardial infarction, either using cardiac enzymes (11.6 vs 14.3 p=0.37) or cardiac enzymes with ECG (8.4 vs 8.4, p=0.99)
  • the rate of stroke (0.4 vs 0.8, p=0.59)
  • the percentage of patients losing of a leg (0.4 vs 0.8, p=0.11)
  • the percentage of patients requirine renal dialysis (0.4 vs 0.4, p=0.97)

Discussion

• The authors of this study conclude that, “Among patients with stable coronary artery disease, coronary artery revascularization before elective major vascular surgery does not improve long term survival”.
• There was no reduction in death, myocardial infarction, or length of stay after vascular surgery in either group.
• This is in line with the current recommendations of the American College of Cardiology, American Heart Association, and American College of Physicians, which only recommend coronary artery revascularization of patients with unstable cardiac symptoms or advances coronary disease that have been proven to have benefit irrespective of future surgery.

THE BOTTOM LINE:  In patients with stable coronary artery disease, preoperative coronary-artery revascularization before non-emergent vascular surgery does not improve the rate of death, decrease the number of postoperative myocardial infarctions or stroke,  decrease the percentage of patients losing a leg, or decrease the need for renal dialysis.