Recurrent Carotid Stenosis Research Articles

Carotid Stents: Unleashed, Unproven

Primarily on the basis of data derived from the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial,1 the US Food and Drug Administration (FDA) has approved the use of carotid stents (CASs) in high-risk patients. The SAPPHIRE trial was published and much heralded as a randomized trial demonstrating that CASs were not inferior to carotid endarterectomy (CEA). Yet, the more recent Endarterectomy Versus Angioplasty in Patients with Symptomatic Carotid Stenosis randomized trial of CASs compared with CEA had to be stopped because the stroke rate with stents was so high that it triggered the safety guidelines of the study design.2 How can we explain the striking difference in outcome between these 2 studies, and how did it happen that the FDA was so convinced of the quality and validity of the SAPPHIRE trial that it granted approval for CASs? An examination of the SAPPHIRE trial—its conduct, data collection and analysis, the circumstances of publication, the presentation to the FDA Advisory Panel, and its consequent approval—is the primary focus of this article. This is a case study of the flaws in our system for the evaluation and approval of medical devices that warrant serious reflection on our ability to properly create and act on accurate information and live up to our commitment to evidence-based decision making. Response by Samuelson et al p 1601 As it now stands, existing studies leave us with the unfortunate but not unreasonable conclusion that no scientific basis exists for the use of CASs as approved by the FDA, and in the absence of change, there is every reason to doubt the capability of our current system to protect the public from unnecessary risk in the future. Although this article focuses on just 1 example of how our systems …

Operative Intervention for Carotid Restenosis is Safe and Effective

Carotid stenting has been proposed as an alternative to reoperative carotid endarterectomy (rCEA) for recurrent carotid stenosis. The purpose of this study is to prove the safety, effectiveness and durability of reoperation in long term follow up of 18 years in a community hospital setting. From March 1988 to April 2005 80 patients, 46 men and 34 women (mean age: 64.1 years) underwent a total of 83 operations. Symptomatic recurrent stenosis (>70%) was the indication in 32, asymptomatic high-grade stenosis (>80%) in 49, intimal flap in one and fibromuscular dysplasia (F.M.D), in one. The initial operation was carotid endarterectomy with primary closure in 60 and prosthetic patch in 23. The mean recurrences were at 23.3 months in 33 with myointimal hyperplasia, 105.4 months in 29 with recurrent atherosclerosis, 61.4 months in 19 with both hyperplasia and atherosclerosis, 2 months in one with intimal flap and 8 months in one with F.M.D bands. Reoperation utilized primary closure (3), vein patch (14), prosthetic patch (55), Gore-Tex interposition grafts (7), vein interposition grafts (3) and intraoperative dilation (1). No perioperative strokes or deaths occurred. One patient died from cardiac complications following combined rCEA and coronary artery bypass grafting. Operative morbidity consisted of reversible nerve injury (5), irreversible recurrent laryngeal nerve injury (1) and hematoma requiring evacuation (3). During follow up (3-153 months; mean: 50.9) carotid occlusion resulted in mild ipsilateral stroke in one patient, and one non-hemispheric stroke. There were 26 late deaths due to all causes, one due to CVA. Eight patients required reoperation (mean 53.4 months). Seven of these were hypertensive. Kaplan-Meier analysis of long-term follow up shows relatively high stroke free rates; at 153 months (12.75 years) the hemispheric stroke free rate was 98.67% and the all-stroke free rate was 95.85%. The survival estimate following redo surgery was 69.97% at 5 years and 40.23% at 10 years. We found that individuals on statin therapy (p-value=0.0042), and those on combination of statin and aspirin (p-value=0.0320), had significantly increased interval between primary and secondary operation. Increased age was correlated to a decreased time to redo surgery (p-value=<0.0001). We conclude that reoperation for recurrent carotid stenosis using standard vascular techniques is safe, effective, durable and cost effective. It should continue to be the mainstay of treatment when secondary intervention is required. Statins have a salutary effect on durability of the procedure and should be used when indicated.

Decreased Antioxidant Vitamin Concentration May Be a Risk Factor for Recurrent Carotid Stenosis

Carotid endarterectomy has been found to be associated with a transient increase in systemic oxidative stress, and this has been shown to be a predictor of restenosis. The aim of this study was to determine the incidence of early recurrent stenosis and investigate a possible role of oxidative stress in its development by measuring the concentration of antioxidant vitamins. Patients undergoing carotid endarterectomy between August 2001 and February 2003 were included in the study. A preoperative blood sample was analyzed for antioxidant vitamin concentrations. All patients were followed up by duplex scans 3 and 12 months postoperatively. Ninety-three patients (101 carotid endarterectomies) were recruited. Nine arteries had developed restenosis by 12 months. Those patients who developed recurrent stenosis had significantly lower vitamin C concentrations (19.10 +/- 3.69 vs 30.11 +/- 19.10, P = .02) than those who did not. This study suggests that low antioxidant vitamin levels may predispose to early restenosis after carotid endarterectomy.

Carotid angioplasty and stenting versus redo endarterectomy for recurrent stenosis

Background Carotid angioplasty and stent (CAS) is an alternative to redo carotid endarterectomy (RCEA) for recurrent carotid stenosis (RCS). The purpose of this study was to evaluate the outcomes of CAS in the treatment of RCS. Methods In an 8-year period, all patients presenting for treatment of RCS were followed-up prospectively. Logistic regression analysis was performed to identify variables associated with unfavorable outcomes. Results There were 45 CAS and 46 RCEA procedures performed in 75 patients. One patient in each group suffered a stroke. There were no deaths. The hospital length of stay was significantly shorter for CAS. Secondary recurrence was higher after RCEA (14% vs 6.1%) and failure to take β-blockers was an independent predictor for multiple recurrences. Conclusions CAS is a safe and effective method to treat patients with RCS and may become the procedure of choice for this disease.

Carotid angioplasty and stent placement for restenosis after endarterectomy

Recurrent carotid stenosis following endarterectomy is a common complication, and reoperation may be associated with increased morbidity. The goal of this study was to determine the procedural safety and long-term complication rates of carotid angioplasty and stenting for recurrent stenosis. Of 248 consecutive carotid angioplasty and/or stenting procedures performed at our institution between March 1996 and November 2005, 83 procedures for recurrent stenosis following endarterectomy were performed in 75 patients (mean age 68 years; 43 men, 32 women) without cerebral protection devices. The patients' medical records were retrospectively reviewed for vascular imaging reports and available clinical follow-up. Procedural and long-term complication rates were calculated. Recurrent stenosis was reduced from a mean of 80.6% to no significant stenosis in 82 of 83 procedures. The procedural stroke rate was 3 out of 83 procedures (3.6%). The procedural transient ischemic attack (TIA) rate was 2 out of 83 procedures (2.4%). Mean follow-up was 22.4 months (range 0.1 to 86.7 months) with at least 6 months follow-up for 54 of 83 procedures (65%). There were five TIAs and no strokes on follow-up (new TIAs at 25.5 and 43.4 months; recurrent TIAs at 1, 11.1, and 12 months, all with normal angiograms). The composite 30-day stroke, myocardial infarction, or death rate was 5 of 83 procedures (6.0%). In this series, angioplasty and stenting were effective in relieving stenosis secondary to recurrent carotid disease after endarterectomy, and have low rates of ischemic complications.

Endovascular and surgical management of carotid artery restenosis

The incidence of recurrent carotid stenosis after primary endarterectomy ranges from 10-34%. We presented our four year experience and comparing reoperation versus endovascular treatment. In period from 2001 to 2005, 50 patients, 37 men and 13 women, were treated surgically and endovascular due to restenosis. There were no minor or major stroke, death and myocardial infarction periprocedural and in first 30 days in either group. In endovascular group one patients 3.17% had transient ischemic attack and two patients 11.76% in surgical group. One patient died from myocardial infraction in follow up in surgical group. There were no restenosis > or = 50% in endovascular group, two patients have restenosis > or = 50% in surgical group. Endovascular treatment of carotid artery restenosis represents a safe and efficient way of treatment, connected with minor number of serious complications than redo operation.

Restenosis after carotid endarterectomy

Multiple randomised trials over the last decade for both symptomatic and asymptomatic carotid stenosis have proven the efficacy of carotid endarterectomy (CE) in reducing the risk of stroke. The long-term patency of the carotid artery after CE is an important factor in the success of the operation. The incidence of recurrent carotid stenosis (excluding residual lesions) ranges from 1 to 37% with only 0-8% of patients having restenosis-related symptoms (1). Generally, recurrent carotid stenosis is attributed to myointimal hyperplasia during the early postoperative period (within 3 years) or recurrent atherosclerosis thereafter. The management of recurrent carotid stenosis after CE remains a dilemma. It is generally accepted that operation for significant recurrent carotid stenosis is indicated for symptomatic patients, and several authors also recommend CE for >80% asymptomatic recurrent stenosis. Treatment of recurrent carotid stenosis involves repeat endarterectomy with patch angioplasty, although more recently endovascular techniques have been used.

Systematic Review of Early Recurrent Stenosis After Carotid Angioplasty and Stenting

Carotid angioplasty and stenting (CAS) has emerged as an alternative to endarterectomy (CEA) for the treatment of carotid artery disease. However, the benefit of CAS is determined by the rate of recurrent carotid stenosis. The authors conducted an analysis of peer-reviewed studies that reported the rate of restenosis exceeding 50% after carotid angioplasty and stenting as determined by duplex ultrasound or angiography. They found 34 studies that met the criteria in which 4185 patients were reported and a follow-up of 3814 arteries occurred over a median of 13 months. The cumuiative restenosis rates were about 6%; and 7.5%9 after 1 and 2 years with a stenosis threshold of between 50% and 70%. The rate was 4% after 2 years in studies with a restenosis threshold of more than 70% to 80%. Although restenosis rates after CAS compare well with those reported for CEA, it appears that the rate might be higher than observational studies have suggested. Follow-up on all stented arteries is advised.

Safety and Efficacy of Eversion Carotid Endarterectomy for the Treatment of Recurrent Stenosis: 20-Year Experience

Current options for treating recurrent carotid stenosis (RCS) include standard longitudinal arteriotomy and patch angioplasty with or without carotid endarterectomy (s-PCEA), carotid-carotid bypass, or carotid angioplasty and stent (CAS). Eversion carotid endarterectomy (e-CEA) is an effective procedure for treating primary carotid stenosis, yet it has not been reported for treating RCS. We evaluated the feasibility and outcome of e-CEA for treating of RCS in comparison to s-PCEA. The records of all patients undergoing elective CEA for symptomatic and asymptomatic high-grade RCS from January 1981 to July 2002 were reviewed. Although during the earlier period s-PCEA was performed preferentially, this paradigm changed to e-CEA being the preferred technique for treatment of RCS. During the course of postoperative follow-up when duplex sonography suggested high-grade RCS, the diagnosis was confirmed via arteriography. Data on cranial nerve injury, recurrent stenosis, stroke, and death were prospectively collected into a vascular registry database and analyzed retrospectively, Students' t-test and chi-square analysis were used to compare the group's baseline characteristics and outcomes. Over a 21-year period, 7001 patients underwent primary CEA for symptomatic (n = 2405, 34%) or asymptomatic (n = 4596, 66%) high-grade stenosis via standard (n = 1501, 21%) or eversion (n = 5500, 79%) techniques. Fifteen (25%) patients had 70 to 80% stenosis, 30 (51%) had 81 to 90% stenosis, and 14 (24%) had 91 to 99% stenosis. During this time period, 59 patients presented with symptomatic (n = 18, 31%) or asymptomatic (n = 41, 69%) high-grade RCS and underwent operative repair via s-PCEA (n = 22, 37%) or eversion (n = 37, 63%) techniques. The mean time interval for repeat carotid surgery for RCS was 49 months in the s-PCEA group and 48 months in the e-CEA group. Permanent cranial nerve injuries, stroke, and recurrent restenosis occurred in one (4.5%), one (4.5%), and one (4.5%) of the patients undergoing s-PCEA, respectively. In the e-CEA group, these events occurred in one (27%), none (0%), and one (2.7%) patients, respectively, There were no deaths during the 30-day postoperative period. Eversion CEA is a feasible option for the treatment of many RCSs and can be performed safely with a low rate of cranial nerve injury, recurrent stenosis, stroke, and death.

Invited commentary

Invited commentary

Safety and efficacy of reoperative carotid endarterectomy: A 14-year experience

Reoperative carotid endarterectomy (CEA) is an accepted treatment for recurrent carotid stenosis. With reports of a higher operative morbidity than primary CEA and the advent of carotid stenting, catheter-based therapy has been advocated as the primary treatment for this reportedly "high-risk" subgroup. This study reviews a contemporary experience with reoperative CEA to validate the high-risk categorization of these patients. From 1989 to 2002, 153 consecutive, isolated (excluding CEA/coronary artery bypass graft and carotid bypass operations) reoperative CEA procedures were reviewed. Clinical and demographic variables potentially associated with the end points of perioperative morbidity, long-term durability, and late survival were assessed with multivariate analysis. There were 153 reoperative CEA procedures in 145 patients (56% men, 36% symptomatic) with an average age of 69 +/- 1.3 years. The average time from primary CEA (68% primary closure, 23% prosthetic, 9% vein patch) to reoperative CEA was 6.1 +/- 0.4 years (range, 0.3 to 20.4 years). At reoperation, patch reconstruction was undertaken in 93% of cases. The perioperative stroke rate was 1.9%, with no deaths or cardiac complications. Other complications included cranial nerve injury (1.3%) and hematoma (3.2%). Average follow-up after reoperative CEA was 4.4 +/- 0.3 years (range, 0.1 to 12.7 years), with an overall total stroke-free rate of 96% and a restenosis rate (>50%) by carotid duplex of 9.2%. Among variables assessed for association with restenosis after reoperative CEA, only younger age was found to be significant (66 +/- 2.5 years vs 70 +/- 0.7 years, P < .05). The all-cause long-term mortality rate was 29%. Multivariate analysis of long-term survival identified diabetes mellitus as having a negative impact (hazard ratio, 3.4 +/- 0.3, P < .05) and lipid-lowering agents as having a protective effect (hazard ratio, 0.42 +/- 0.4, P < .05) on survival. Reoperative CEA is a safe and durable procedure, comparable to reported standards for primary CEA, for long-term protection from stroke. These data do not support the contention that patients who require reoperative CEA constitute a "high-risk" subgroup in whom reoperative therapy should be avoided.

Determinants of carotid endarterectomy anatomic durability: Effects of serum lipids and lipid-lowering drugs

Carotid endarterectomy (CEA) remains the gold standard for treatment of carotid stenosis. With inevitable comparisons of catheter-based therapy to all aspects of CEA, this study of a large contemporary series was undertaken to evaluate the determinants of anatomic durability of CEA. During the interval (1989 through 1999), 2,127 primary, isolated CEAs with selective patching (50.2%) were performed in 1,853 patients (61.8% male, 36.1% symptomatic). End points included patient longevity and perioperative morbidity as well as evidence of CEA anatomic durability as defined by duplex evaluation: CEA restenosis (moderate, >50%, or greater recurrent stenosis), which included CEA anatomic failure (severe, >70%, restenosis/carotid occlusion). The incidence of CEA recurrent stenosis was temporally assessed early (<2 years) and late (>2 years) after operation. Clinical and surgical variables potentially associated with the study endpoints were analyzed by univariate and multivariate methods. The perioperative stroke and death rate was 1.4% and the 2-year and 10-year survival was 88.1% and 44.9%, respectively. Anatomic failure after CEA developed in 3.9% at 2 years and in 8.5% at 5 years; only 3.2% of CEA patients underwent reoperation during a mean follow-up of 73.4 months. Early (<2 years) analysis revealed 12.2% restenosis, whereas late (>2 years) results identified 9.8% progression of carotid stenosis and a 5.8% rate of anatomic failure. Multivariate analysis determined elevated creatinine (odds ratio [OR], 1.719, P < .001) and female gender (OR, 1.564; P < .02) correlated with early restenosis. Surgical patch closure and lipid-lowering drugs were protective for both early restenosis, with ORs of 0.543 (P < .0.001) and 0.601 (P < .007) and early anatomic failure ORs of 0.469 (P < .02) and 0.517 (P < .03), respectively. Although only elevated serum cholesterol (OR, 1.009; P < .03) correlated with late anatomic failure, only lipid-lowering drugs were protective for both late freedom from progression of disease (OR, 0.202; P < .0002) or late CEA anatomic failure (OR, 0.128; P < .0003). The association of female gender and elevated cholesterol with recurrent carotid stenosis is confirmed, elevated creatinine is introduced as a risk factor, and surgical patch repair is protective for early CEA recurrent carotid stenosis. The unique findings of the significant, beneficial effects of lipid-lowering drugs on both early and late CEA anatomic durability and patient survival indicate that such therapy should be instituted in most patients after CEA.

Recurrent carotid stenosis after angioplasty and stenting

Recurrent carotid stenosis after angioplasty and stenting

Carotid Artery Pseudoaneurysm after Endovascular Stent Placement: Diagnosis and Follow-up Duplex Ultrasonography

Purpose Carotid artery pseudoaneurysm development after endarterectomy, albeit rare, has been attributed to patch deterioration. We present an unusual case of pseudoaneurysm development 1 year after stent placement for recurrent carotid artery stenosis. Case Report A 64-year-old man had transient hemiparesis develop 1 week after carotid artery endarterectomy (CEA) with patch angioplasty for monocular transient ischemic attack. Carotid angiography reviewed an intimal flap at the distal endarterectomy site, which was successfully treated with carotid stent placement. During a duplex scan 1 year later, he was found to have a symptomatic 2.5-cm pseudoaneurysm at the level of stented carotid bifurcation. This was successfully treated with a combined open and endovascular approach, which consisted of stent-graft placement by means of an open carotid exposure. Completion angiogram showed successful stent-graft exclusion of the pseudoaneurysm. A follow-up duplex scan 6 months later demonstrated diminution of pseudoaneurysm size without endoleak. Conclusion This report highlights the importance of duplex ultrasound surveillance in patients with CEA or carotid stenting, because it can accurately detect recurrent stenosis or carotid pseudoaneurysm. Moreover, a combined open and endovascular therapy using stent graft successfully treated the carotid pseudoaneurysm in our patient.

Recurrent Carotid Artery Stenosis Following Endarterectomy: Natural History and Risk Factors

ObjectivesTo establish the incidence of restenosis (RES) following carotid endarterectomy (CEA) and evaluate clinical and technical factors related to its development. DesignProspective non-randomised cohort study. Patients and methodsTwo hundred and twenty-four patients with 243 CEA between May 1998 and December 2002, were subjected to clinical and haemodynamic follow-up, median follow-up 23 months (1–56). There was selective use of a shunt (17.3%) and patch (61.7%). RES (≥50%) and severe restenosis, ≥70%, (sRES) were defined as peak systolic velocities of ≥150 and ≥300cm/s (or ≥250cm/s with diastolic velocity >100cm/s), respectively. Rates of RES, symptom development and mortality were analysed using Kaplan–Meier curves. Cox's regression model (hazards ratio/95% CI) was used to evaluate prognostic factors. ResultsWe detected 13 sRES (5.3%) (median time 6.1 months) and 30 (12.3%) moderate stenosis (mRES) (median time 3.7 months). Cumulative freedom from sRES at 23 months was 94.2%. Five sRES detected in the first 45 days after the procedure were deemed to be residual restenosis (rRES). Five (38.4%) sRES were symptomatic, 15.3% progressed to occlusion. Patient survival was 98.0 and 96.4% at 12 and 24 months, respectively. Independent risk factors for sRES: female sex (HR: 3.3, 95% CI 1.1–10 p=0.04) and diabetes (HR: 4.5, 95% CI 1.4–13.9 p=0.008). ConclusionsCarotid restenosis appears early, is usually low-grade and mostly asymptomatic. Although few stenoses progress to occlusion, women and diabetic patients were at highest risk.

Factors Affecting Recurrent Carotid Stenosis

Recurrent carotid stenosis is an ongoing process that may develop at or near the site of an operational or interventional procedure to treat an atheromatous stenosis. Although such a restenosis is most often initially without symptoms, as the disease progresses it may become symptomatic, and thus endanger the patient's life. Such patients are therefore candidates for revisional surgery. Extensive research investigation and numerous studies have incriminated several risk factors as predisposing conditions for recurrent carotid stenosis. The definite role of each predisposing factor, however, is still widely debated. Clarifying the extent of involvement of each factor in the pathogenesis of carotid restenosis is indeed demanding, as it would contribute enormously to the identification of the group of high-risk patients, and, therefore, determine the therapeutic approach in these patients.

Systematic Review of Early Recurrent Stenosis After Carotid Angioplasty and Stenting

Carotid angioplasty and stenting (CAS) has emerged as a potential alternative to endarterectomy (CEA) for the treatment of carotid artery disease. Aside from the periprocedural complication rates, the benefits of CAS will be affected by the incidence of recurrent carotid stenosis. We conducted a systematic analysis of all peer-reviewed studies reporting on the rate of restenosis (> or =50%) after CAS based on duplex ultrasound or angiography that were published between January 1990 and July 2004. We identified 34 studies that reported on a total of 4185 patients with a follow-up of 3814 arteries over a median of 13 months (range, 6 to 31 months). The ultrasound criteria and the lower thresholds for defining a recurrent stenosis were very heterogeneous. The cumulative restenosis rates after 1 and 2 years were approximately 6% and 7.5% in those studies, which used a lower restenosis threshold > or =50% to 70% and approximately 4% in the first 2 years after CAS in those studies, which used a lower restenosis threshold >70% to 80%. In reviewing the current literature, the early restenosis rates after CAS compare well with those reported for CEA. However, this analysis of the peer-reviewed literature also indicates that the early restenosis rates after CAS might be higher than previously suggested in observational surveys. Therefore, an active follow-up of all stented arteries seems to be warranted. Moreover, the bulk of endovascular data are derived from small studies with short follow-up periods so that the long-term durability of CAS still needs to be established in large trials. Ideally, these studies should use a clear and uniform definition of restenosis and identical follow-up schedules.

Carotid angioplasty: The need to revise post surgical duplex velocity criteria

Purpose. To determine the appropriate duplex velocities post carotid artery angioplasty and stent compared with endarterectomy for recurrent stenosis. Methods. Retrospective analysis on patients with over 80% recurrent carotid artery stenosis treated at our institution was performed. Velocities from preoperative, postoperative (<1 week), and late postoperative duplex scans (1–121 months) were compared after re-do carotid endarterectomy (CEA) or carotid artery angioplasty and stent (CAS) placement. Variables within the groups were compared using analysis of variance (ANOVA). Stepwise-regression analysis was used to determine the independence of CAS as a factor causing elevated postoperative velocities. Mean peak systolic velocities (PSV) ± SEM, end diastolic velocities (EDV) ± SEM, and internal carotid artery/common carotid artery PSV ratios (ICA/CCA) are reported. Results. Thirty-four patients with a mean age of 72 were studied. Sixteen patients underwent CAS, and 18 patients underwent CEA. The mean interval between first CEA and treatment for the recurrent stenosis (CEA or CAS) was 41 months. There was no significant difference in risk factors between groups (age, gender, patch, and contralateral occlusion). There was a significant difference in postoperative PSV between CEA and CAS, which resolved after 1.5 years. Similarly, the postoperative ICA/CCA was significantly different between CEA and CAS (0.97 ± 0.11 versus 1.48 ± 0.20, respectively, P < 0.05, ANOVA). When controlled for contralateral occlusion and interval (months) between procedures, CAS over CEA was found to be independently associated with elevated ICA/CCA ratios using linear regression analysis. Conclusion. Postoperative duplex velocities after CAS may not represent hemodynamic narrowing but may indicate altered biomechanics of the poststented carotid. TABLE—ABSTRACT 35 PSV (cm/s) EDV (cm/s) preop (n) postop (n) longterm (n) preop (n) postop (n) longterm (n) CEA 278 ± 38 102 ± 11 113 ± 12 90 ± 14 24 ± 4 28 ± 4 (18) (14) (12) (18) (14) (12) CAS 364 ± 47 ∗145 ± 18 116 ± 11 111 ± 15 30 ± 4 32 ± 3 (15) (17) (12) (15) (17) (12) Note. Mean ± SEM. ∗ P < 0.05 between CAS and CEA.

Antithrombotic Therapy in Peripheral Arterial Occlusive Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

This chapter about antithrombotic therapy for peripheral arterial occlusive disease is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs, and Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004;126:179S-187S). Among the key recommendations in this chapter are the following: For patients with chronic limb ischemia, we recommend lifelong aspirin therapy in comparison to no antiplatelet therapy in patients with clinically manifest coronary or cerebrovascular disease (Grade 1A) and in those without clinically manifest coronary or cerebrovascular disease (Grade 1C+). We recommend clopidogrel over no antiplatelet therapy (Grade 1C+) but suggest that aspirin be used instead of clopidogrel (Grade 2A). For patients with disabling intermittent claudication who do not respond to conservative measures and who are not candidates for surgical or catheter-based intervention, we suggest cilostazol (Grade 2A). We suggest that clinicians not use cilostazol in patients with less-disabling claudication (Grade 2A). In these patients, we recommend against the use of pentoxifylline (Grade 1B). We suggest clinicians not use prostaglandins (Grade 2B). In patients with intermittent claudication, we recommend against the use of anticoagulants (Grade 1A). In patients with acute arterial emboli or thrombosis, we recommend treatment with immediate systemic anticoagulation with unfractionated heparin (UFH) [Grade 1C]. We also recommend systemic anticoagulation with UFH followed by long-term vitamin K antagonist (VKA) in patients with embolism [Grade 1C]). For patients undergoing major vascular reconstructive procedures, we recommend UFH at the time of application of vascular cross-clamps (Grade 1A). In patients undergoing prosthetic infrainguinal bypass, we recommend aspirin (Grade 1A). In patients undergoing infrainguinal femoropopliteal or distal vein bypass, we suggest that clinicians do not routinely use a VKA (Grade 2A). For routine patients undergoing infrainguinal bypass without special risk factors for occlusion, we recommend against VKA plus aspirin (Grade 1A). For those at high risk of bypass occlusion and limb loss, we suggest VKA plus aspirin (Grade 2B). In patients undergoing carotid endarterectomy, we recommend aspirin preoperatively and continued indefinitely (Grade 1A). In nonoperative patients with asymptomatic or recurrent carotid stenosis, we recommend lifelong aspirin (Grade 1C+). For all patients undergoing extremity balloon angioplasty, we recommend long-term aspirin (Grade 1C+).

Homocysteine, a risk factor for carotid atherosclerosis, is not a risk factor for early recurrent carotid stenosis following carotid endarterectomy.

Homocysteine has been proposed as a risk factor for atherosclerotic disease and recurrent coronary stenosis due to neointimal hyperplasia following angioplasty. In order to evaluate homocysteine's role in human carotid neointimal hyperplasia, we have compared homocysteine levels in patients who have not developed restenosis with those who have within 2 years of carotid endarterectomy (CEA). One hundred and fifty-four patients were divided into 3 groups based on duplex scans performed 2 years after CEA. Group I (88) were patients in whom all scans showed no evidence of restenosis. Group II (35) patients exhibited some restenosis, but this did not exceed 49% diameter reduction based on our duplex criteria. Group III (31) patients developed a restenosis of > 50% within 2 years. One hundred and thirteen Dacron patches (73 Group I [83%], 22 Group II [63%], and 18 Group III [58%]) were used according to surgeon preference but did not affect the statistical relevance of homocysteine evaluation. The groups were otherwise identical in terms of age, sex, smoking history, and cholesterol levels. All patients were receiving antiplatelet medication postoperatively, and none had consumed added pharmacologic folate. The average homocysteine value for the entire study group was elevated at 12.5 micromol/L. The homocysteine values for the 3 groups were not statistically different (p > 1): (I, 12.5; II, 12.2; and III, 12.9 micromol/L). Elevated homocysteine levels (> 10 micromol/L) appear to be associated with carotid atherosclerosis, but at levels < 30 micromol/L do not appear to play a role in restenosis following CEA.