A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial. A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion. Potential use of a low-molecular-weight heparin to prevent restenosis in patients with extensive wall damage following peripheral angioplasty. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
The EVEREST Trial was designed to determine whether the surgical technique influences the durability and complications of carotid endarterectomy (CEA). The current report focuses on the study design and preliminary results.
                EVEREST is a randomized multicenter trial. A total of 1353 patients with carotid stenosis requiring surgical treatment were randomly assigned to received standard (n = 675) or eversion (n = 678) CEA. Primary end points included carotid occlusion, major stroke, death, and restenosis rate.
                The rate of perioperative major stroke and death (1.3 for each study group) and the incidence of early carotid occlusion (0.6% for eversion vs 0.4% for standard) were similar. No significant differences were found between eversion and standard CEA with respect to incidence of perioperative transient ischemic accident, minor stroke, cranial nerve injuries, neck hematoma, myocardial infarction, or surgical defects as detected with intraoperative quality controls. Clamping time was significantly shorter for eversion CEA compared with patch standard procedures (31.7 +/- 15.9 vs 34.5 +/- 14.4 minutes, p = 0.02). A shunt was inserted in 11% of patients undergoing eversion CEAs and in 16% of patients undergoing standard procedures. Overall 30-day events occurred in 13.3% of the eversion group and in 11.4% of the standard group (p = 0.3). At a mean follow-up of 14.9 months (range, 1 to 38 months), 16 (2.4%) restenoses occurred in the eversion group and 28 (4.1%) occurred in the standard group (odds ratio, 0.56; 95% confidence interval, 0.3 to 1.1; p = 0.08).
                The preliminary results of the EVEREST Trial suggest that eversion CEA is a safe and rapid procedure with low major complication rates. No significant differences in restenosis rates were observed between eversion and standard CEA at the available follow-up. Longer-term results are necessary to assess whether the eversion technique influences the durability of CEA. To compare the clinical outcome and restenosis incidence of patients who underwent carotid endarterectomy with patch closure (CEAP) on one side and carotid eversion endarterectomy (CEE) on the other.
                Although a few investigators have compared the results of CEAP versus CEE, no reports have compared the outcome of CEAP versus CEE in the same patient.
                Eighty-six patients were randomly selected for sequential surgical treatment involving either CEAP/CEE or CEE/CEAP. All patients underwent postoperative duplex ultrasound study and clinical follow-up at 1, 6, and 12 months and every year thereafter. Various factors were analyzed to ascertain any association with restenosis, and Kaplan-Meier analysis was used to estimate the risk of restenosis.
                Demographic and clinical data were similar in the CEAP and CEE groups. The selective shunting rate was statistically higher in the CEAP group. There were no perioperative deaths. Although the incidence of perioperative ipsilateral stroke was not significant, CEAP patients had a rate of combined transient ischemic attacks and strokes that approached statistical significance. The mean follow-up was 40 months. CEAP patients had a significantly higher incidence of restenosis and combined occlusive events and restenoses. Kaplan-Meier analysis showed that CEE had a significantly better cumulative patency rate than CEAP and that freedom from restenoses at 24 and 36 months was 87% and 83% for CEAP and 98% and 98% for CEE, respectively.
                CEE is less likely to cause perioperative neurologic complications and restenoses than CEAP. The significantly higher rate of unilateral recurrence suggests that local factors play a more important role than systemic factors in the occurrence of restenosis. The long-term outcome of primary successful percutaneous transluminal angioplasty (PTA) for patients with peripheral occlusive arterial disease (POAD) is frequently compromised by the development of restenosis, especially when extensive dissections result from the angioplastic procedure. Unfortunately, prevention of the occlusive process by means of drugs such as antithrombotics, anticoagulants, thrombolytics, corticosteroids, lipid reducers, or cytostatics has not been demonstrated convincingly. The authors sought to clarify whether such patients could benefit from the postsurgical administration of low-molecular-weight heparin. A total of 172 POAD patients with extensive dissections after PTA in the pelvic or upper leg regions were randomized for 7-day post-PTA intravenous treatment with either full heparinization or nadroparin calcium followed by adjunctive oral aspirin for 6 months. The primary outcome measure was the degree of stenosis (normal findings; stenosis < 50%, > 50%, > 80%, occlusion) before and after angioplasty, as well as 3 weeks and 3 and 6 months after dilation; secondary efficacy criteria included changes in the Fontaine stage and in the crurobrachial ratio. No significant treatment-related differences were found at the 3 post-PTA follow-up examinations with regard to the degree of stenosis. This was also the case for the subgroup of patients (n = 62) who had undergone angioplasty in the pelvic region. By contrast, when angioplasty was performed in the superficial femoral artery (n = 110), the degree of restenosis was significantly lower (p<0.01) among patients receiving nadroparin calcium compared to those given heparin at week 3, month 3, and month 6. No intergroup differences emerged for secondary outcome measures in the long term or for safety parameters. These preliminary results indicate that patients with extensive dissections after PTA treatment for POAD in the upper leg region might benefit from a reduction in the rate of restenosis by administration of 7-day weight-adjusted nadroparin calcium. Among patients with substantial carotid artery narrowing but no recent neurological symptom (stroke or transient ischaemia), the balance of surgical risks and long-term benefits from carotid endarterectomy (CEA) was unclear.
                During 1993-2003, 3120 asymptomatic patients with substantial carotid narrowing were randomised equally between immediate CEA (half got CEA by 1 month, 88% by 1 year) and indefinite deferral of any CEA (only 4% per year got CEA) and were followed for up to 5 years (mean 3.4 years). Kaplan-Meier analyses of 5-year risks are by allocated treatment.
                The risk of stroke or death within 30 days of CEA was 3.1% (95% CI 2.3-4.1). Comparing all patients allocated immediate CEA versus all allocated deferral, but excluding such perioperative events, the 5-year stroke risks were 3.8% versus 11% (gain 7.2% [95% CI 5.0-9.4], p<0.0001). This gain chiefly involved carotid territory ischaemic strokes (2.7% vs 9.5%; gain 6.8% [4.8-8.8], p<0.0001), of which half were disabling or fatal (1.6% vs 5.3%; gain 3.7% [2.1-5.2], p<0.0001), as were half the perioperative strokes. Combining the perioperative events and the non-perioperative strokes, net 5-year risks were 6.4% versus 11.8% for all strokes (net gain 5.4% [3.0-7.8], p<0.0001), 3.5% versus 6.1% for fatal or disabling strokes (net gain 2.5% [0.8-4.3], p=0.004), and 2.1% versus 4.2% just for fatal strokes (net gain 2.1% [0.6-3.6], p=0.006). Subgroup-specific analyses found no significant heterogeneity in the perioperative hazards or (apart from the importance of cholesterol) in the long-term postoperative benefits. These benefits were separately significant for males and females; for those with about 70%, 80%, and 90% carotid artery narrowing on ultrasound; and for those younger than 65 and 65-74 years of age (though not for older patients, half of whom die within 5 years from unrelated causes). Full compliance with allocation to immediate CEA or deferral would, in expectation, have produced slightly bigger differences in the numbers operated on, and hence in the net 5-year benefits. The 10-year benefits are not yet known.
                In asymptomatic patients younger than 75 years of age with carotid diameter reduction about 70% or more on ultrasound (many of whom were on aspirin, antihypertensive, and, in recent years, statin therapy), immediate CEA halved the net 5-year stroke risk from about 12% to about 6% (including the 3% perioperative hazard). Half this 5-year benefit involved disabling or fatal strokes. But, outside trials, inappropriate selection of patients or poor surgery could obviate such benefits.
Eversion CEA may be associated with low risk of arterial occlusion and restenosis. However, numbers are too small to definitively assess benefits or harms. Reduced restenosis rates did not appear to be associated with clinical benefit in terms of reduced stroke risk, either perioperatively or later. Until further evidence is available, the choice of the CEA technique should depend on the experience and familiarity of the individual surgeon.