Enrico Cieri

Comparison of Surveillance Versus Aortic Endografting for Small Aneurysm Repair (CAESAR): Results from a Randomised Trial

BACKGROUND Randomised trials have failed to demonstrate benefit from early surgical repair of small abdominal aortic aneurysm (AAA) compared with surveillance. This study aimed to compare results after endovascular aortic aneurysm repair (EVAR) or surveillance in AAA <5.5 cm. METHODS Patients (50-79 years) with AAA of 4.1-5.4 cm were randomly assigned, in a 1:1 ratio, to receive immediate EVAR or surveillance by ultrasound and computed tomography (CT) and repair only after a defined threshold (diameter ≥5.5 cm, enlargement >1 cm /year, symptoms) was achieved. The main end point was all-cause mortality. Recruitment is closed; results at a median follow-up of 32.4 months are here reported. RESULTS Between 2004 and 2008, 360 patients (early EVAR = 182; surveillance = 178) were enrolled. One perioperative death after EVAR and two late ruptures (both in the surveillance group) occurred. At 54 months, there was no significant difference in the main end-point rate [hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.30-1.93; p = 0.6] with Kaplan-Meier estimates of all-cause mortality of 14.5% in the EVAR and 10.1% in the surveillance group. Aneurysm-related mortality, aneurysm rupture and major morbidity rates were similar. Kaplan-Meier estimates of aneurysms growth ≥5 mm at 36 months were 8.4% in the EVAR group and 67.5% in the surveillance group (HR 10.49; 95% CI 6.88-15.96; p < 0.01). For aneurysms under surveillance, the probability of delayed repair was 59.7% at 36 months (84.5% at 54 months). The probability of receiving open repair at 36 months for EVAR feasibility loss was 16.4%. CONCLUSION Mortality and rupture rates in AAA <5.5 cm are low and no clear advantage was shown between early or delayed EVAR strategy. However, within 36 months, three out of every five small aneurysms under surveillance might grow to require repair and one out of every six might lose feasibility for EVAR. Surveillance is safe for small AAA if close supervision is applied. Long-term data are needed to confirm these results. CLINICAL TRIAL REGISTRATION INFORMATION This study is registered, NCT Identifier: NCT00118573.

Type II endoleak is an enigmatic and unpredictable marker of worse outcome after endovascular aneurysm repair

BACKGROUND This study analyzed predictors and the long-term consequence of type II endoleak in a large series of elective endovascular abdominal aneurysm repairs (EVARs). METHODS Baseline characteristics and operative and follow-up data of consecutive patients undergoing EVAR were prospectively collected. Patients who developed type II endoleak according to computed tomography angiography and those without type II endoleak were compared for baseline characteristics, mortality, reintervention, conversion, and aneurysm growth after repair. RESULTS In 1997-2011, 1412 consecutive patients (91.4% males; mean age, 72.9 years) underwent elective EVAR and were subsequently followed up for a median of 45 months (interquartile range, 21-79 months). Type II endoleak developed in 218. Adjusted analysis failed to identify significant independent predictors for type II endoleak with the exception of age (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .003) and intraluminal thrombus (odds ratio, 0.69; 95% confidence interval, 0.53-0.92; P = .010). Type II endoleak rates were comparable regardless of the device model. Late aneurysm-related survival was comparable (98.4% vs 99.5% at 60 months; P = .73) in patients with and without type II endoleak. However, at 60 months after EVAR, rates of aneurysm sac growth >5 mm (35.3% vs 3.3%; P < .0001) were higher in patients with type II endoleak. Cox regression identified type II endoleak as an independent predictor of aneurysm growth along with age and cardiac disease. The presence of type II endoleak led to reinterventions in 40% of patients and conversion to open surgery in 8%. However, assessment of these patients after reintervention showed similar 60-month freedom rates of persisting type II endoleak (present in more than two after computed tomography angiography scan studies) among those with and without reinterventions (49.8% vs 45.6%; P = .639). Aneurysm growth >5 mm persisted with comparable rates in type II endoleak patients after reintervention and in those who remained untreated (42.9% vs 57.4% at 60 months; P = .117). CONCLUSIONS Reintervention for type II endoleak was common in our practice, yet such intervention did not reliably prevent the continued expansion of the abdominal aortic aneurysm. Our data indicate type II endoleak appears to be a marker of EVAR failure that is difficult to predict and treat effectively.

Effects of statins on early and late results of carotid stenting

OBJECTIVES Increasing data suggest that statins can significantly decrease cardiovascular and cerebrovascular events due to a plaque stabilization effect. However, the benefit of statins in patients undergoing carotid angioplasty and stenting (CAS) for carotid stenosis is not well defined. The aim of this study was to investigate whether statins use was associated with decreased perioperative and late risks of stroke, mortality, and restenosis in patients undergoing CAS. METHODS All patients undergoing CAS for primary carotid stenosis from 2004 to 2009 were reviewed. The independent association of statins and perioperative morbidity was assessed using multivariable analysis. Survival curves and Cox regression models were used to assess late morbidity and restenosis. Propensity score adjustment was employed. RESULTS A total of 1083 consecutive CAS were performed (29% females, mean age 71.5 years; 24.7% symptomatic); 465 (43%) were on statins medication before treatment that was not discontinued at discharge. Statins use was associated with a reduction of perioperative stroke and death (odds ratio [OR] 0.327, 95% confidence interval [CI] 0.13-0.80, P = .016) according to multivariable analysis. Statins effect was more significant in reducing stroke and death in symptomatic patients (OR 0.13; P = .032) and in males (OR 0.27, P = .01). At 5 years, survival (87.2% vs 78.3%; P = .009) and ischemic stroke-free interval (88.9% vs 99.7%; P = .02) rates were higher in the statins group of patients. Adjusting for propensity score and covariates in Cox regression analyses, statins use was independently associated with reduced long-term mortality risk (HR 0.56, 95% CI 0.32-0.97; P = .039) and borderline associated with decreased late ischemic stroke risk (HR 0.14; 95% CI 0.018-1.08, P = .059). There was no effect on restenosis rates. CONCLUSIONS These data suggest that statins use is associated with decreased perioperative and late ischemic strokes risk and reduced mortality rates in patients undergoing CAS. Statins therapy should be considered part of the best medical treatment in current CAS practice.

Is Haemodynamic Depression during Carotid Stenting a Predictor of Peri-procedural Complications?

OBJECTIVE The clinical significance of Haemodynamic Depression (HD) during carotid stenting (CAS) remains unclear. The aim of this study was to analyze the frequency and predictors of HD during CAS in a single centre experience. METHODS A prospective protocol for CAS was applied in a 15-month interval. Patients with restenosis, on betablockers, or with arrhythmias were excluded. A standardized dose of atropine (0.4mg) was given prior to stent deployment. Changes in heart rate, blood pressure, and neurological status were monitored and recorded. HD was defined as systolic pressure <90mmHg and/or heart rate <50 beats/min. Fifteen potential predictors of HD (age, gender, hypertension, smoking, diabetes, coronary artery disease, previous myocardial infarction, symptoms, degree of carotid stenosis contralateral CEA or CAS, calcified/hyperechoic plaque, plaque length, stent oversizing and type of stent) were tested in multivariate analysis. RESULTS Two hundred and twenty three consecutive patients were enrolled. HD occurred in 98 cases (44%): in 68 cases HD required additional pharmacological support. At 30 days, any stroke rate was 3.1% (3 major and 4 minor), TIA rate 1.8%, myocardial infarction rate 0.4%. No deaths were recorded. No difference in complication rates were found in patients with or without HD. From regression analysis only the presence of calcified plaque (HR 9.5; 95% CI 5.0 to 18.2; p<0.0001) and the plaque length (HR 1.77; 95% CI 1.03 to 3.06; p=0.038) were associated significantly with HD. CONCLUSIONS HD during CAS is a common, relatively benign event, without increased risk of peri-operative complications. Careful pharmacological treatment is necessary to decrease HD and the potential complications, especially in patients with more severe calcified lesions. These results require confirmation in a separate, larger cohort.

Quality of life in patients with small abdominal aortic aneurysm: the effect of early endovascular repair versus surveillance in the CAESAR trial.

OBJECTIVE To evaluate and compare changes over time in health-related quality of life reported by patients with small (4.1-5.4 cm) abdominal aortic aneurysms (AAAs) undergoing endovascular aortic aneurysm repair (EVAR) or surveillance. METHODS Participants were randomly assigned to receive either early EVAR or surveillance within a multicentre, randomised clinical trial on small AAA (Comparison of surveillance vs. Aortic Endografting for Small Aneurysm Repair, CAESAR). Patient-reported health-related quality of life was assessed before randomisation, at 6 months and yearly thereafter using the Short Form 36 (SF-36) Health Survey. RESULTS Between 2004 and 2008, 360 patients (345 males, mean age 68.9 years) were randomised, 182 to early EVAR and 178 to surveillance. There was one perioperative death. Mean follow-up was 31.8 months. No significant difference in survival was found. At baseline, comparable quality of life scores were recorded in both treatment groups: Total SF-36: 73.0 versus 75.5 (p = 0.18), Physical domain: 71.4 versus 73.3 (p = 0.33); Mental health domain: 70.9 versus 72.7 (p = 0.33), in the EVAR arm versus the surveillance arm, respectively. Six months after randomisation, Total SF-36 and Physical and Mental domain scores were all significantly higher with respect to baseline in the EVAR group, while patients of the surveillance group scored lower. The differences between EVAR and surveillance arms in score changes at 6 months were significant and in favour of EVAR: Total score: difference 5.4; p = 0.0017; Physical: difference 3.8; p = 0.02; and Mental: difference 6.0; p = 0.0005. Differences between EVAR and surveillance diminished over time. At the last assessment, patients in both groups had decreased scores with a significant drop with respect to the baseline (-3.9 in EVAR, -6.3 in surveillance). There were no significant differences between the EVAR and surveillance arms: Total score: p = 0.25; Physical: p = 0.47; and Mental: p = 0.38. CONCLUSIONS Patients with small AAA under surveillance compared with early EVAR had significant impaired functional health at 6 months after assignment. After a mean of 31.8 months, SF-36 health-related quality of life in patients allocated to early EVAR and surveillance was similar.

Effects of diabetes on small aortic aneurysms under surveillance according to a subgroup analysis from a randomized trial

BACKGROUND This study aims to investigate the impact of diabetes in the management of patients with small abdominal aortic aneurysms (AAA). METHODS Three-hundred sixty patients with small AAA (4.1-5.4 cm), enrolled in a randomized trial comparing early endovascular repair versus surveillance and delayed repair (after achievement of >5.5 cm or growth>1 cm/yr), were analyzed with standard survival methods to assess the relation between diabetes and risk of all-cause mortality, complications, and aneurysm growth (on computed tomography as per trial protocol) at 36 months. Baseline covariates were selected with partial likelihood stepwise method to investigate factors (demographic, morphologic, medications) associated with risk of aneurysm growth during surveillance. RESULTS Prevalence of diabetes was 13.6%. The hazard ratio (HR) for all-cause mortality at 36 months was higher in diabetic compared with nondiabetic patients: (HR, 7.39; 95% confidence interval [CI], 1.55-35.13; P=.012). Baseline aneurysm diameter was comparable between diabetic and nondiabetic patients enrolled in the surveillance arm and was related to subsequent aneurysm growth in covariance analyses adjusted for diabetes (49.3 mm for nondiabetic; 50.2 mm for diabetic). Cox analyses found diabetes as the strongest independent negative predictor of 63% lower probability of aneurysm growth>5 mm during surveillance (HR, 0.37; 95% CI, 0.15-0.92; P=.003). Kaplan-Meier cumulative probability of aneurysm growth>5 mm at 36 months was 40.8% in diabetics versus 85.1% in nondiabetics (HR, 0.32; 95% CI, 0.17-0.61). CONCLUSIONS Progression of small AAA seems to be more than 60% lower in patients with diabetes. This may help to identify high-risk subgroups at higher likelihood of AAA enlargement, such as nondiabetics, for surveillance protocols in patients with small AAA.

Diabetes is not a predictor of outcome for carotid revascularization with stenting as it may be for carotid endarterectomy

BACKGROUND Diabetes is prevalent in most patients undergoing carotid revascularization and is suggested as a marker of poor outcome after carotid endarterectomy (CEA). Data on outcome of diabetic patients undergoing carotid artery stenting (CAS) are limited. The aim of this study was to investigate early and 6-year outcomes of diabetic patients undergoing carotid revascularization with CAS and CEA. METHODS The database of patients undergoing carotid revascularization for primary carotid stenosis was queried from 2001 to 2009. Diabetic patients were defined as those with established diagnosis and/or receiving oral hypoglycemic or insulin therapy. Multivariate and Kaplan- Meier analyses, stratified by type of treatment, were performed on perioperative (30 days) and late outcomes. RESULTS A total of 2196 procedures, 1116 by CEA and 1080 by CAS (29% female, mean age 71.3 years), were reviewed. Diabetes was prevalent in 630 (28.7%). Diabetic patients were younger (P < .0001) and frequently had hypertension (P = .018) or coronary disease (P = .019). Perioperative stroke/death rate was 2.7% (17/630) in diabetic patients vs 2.3% (36/1566) in nondiabetic, (P = .64); the rate was 3.4% in diabetic CEA group and 2.1% in diabetic CAS group (P = .46). At multivariate analyses, diabetes was a predictor of perioperative stroke/death in the CEA group (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.05-7.61; P = .04) but not in the CAS group (P = .72). Six-year survival was 76.0% in diabetics and 80.8% in nondiabetics (P = .15). Six-year late stroke estimates were 3.2% in diabetic and 4.6% in nondiabetic patients (P = .90). The 6-year risk of restenosis was similar (4.6% % vs 4.2%) in diabetic and nondiabetic patients (P = .56). Survival, late stroke, and restenosis rates between diabetics and nondiabetics were similar in CAS and CEA groups. CONCLUSIONS Diabetic patients are not at greater risk of perioperative morbidity and mortality or late stroke after CAS, however, the perioperative risk can be higher after CEA. This may help in selecting the appropriate technique for carotid revascularization in patients best suited for the type of procedure.

Safety of Carotid Stenting (CAS) is Based on Institutional Training More than Individual Experience in Large-volume Centres

BACKGROUND Operator training is a key factor for the safety of carotid stenting (CAS). Whether institutional practice is associated with improved individual operator outcomes is debated. OBJECTIVE To evaluate the effect of the institutional experience on outcomes of new trainees with CAS, a retrospective analysis of a prospectively held database was performed. METHODS The overall study period, 2004-2012, was divided into two sequential time frames: 2004-April 2006 (leaders-team phase) and May 2006-2012 (expanded team phase). In the first frame, a single leader-operators team that first approached CAS and passed the original institutional learning curve, performed all the procedures; in the following expanded-team phase, five new trainees joined. Institutional CAS training for new trainees was based on a team-working approach including selection of patients, devices and techniques and collegial meetings with critical review and discussion of all procedural steps and imaging. RESULTS A total of 431 CAS procedures were performed in the leaders-team phase and 1026 in the sequential expanded-team phase. Periprocedural complication rates in the two time frames were similar: stroke/death (3.0% vs. 2.1%; P = 0.35), stroke (2.8% vs. 2.1%; P = 0.45) major stroke (0.9% vs. 0.6%, P = 0.49), death (0.2% vs. 0%; P = 0.29) during the leaders-team and expanded-team phase, respectively. However, rates of CAS failure requiring surgical conversions (3.7% vs. 0.8%; P < 0.0001) and mean contrast use (91.6 vs. 71.1 ml; P = 0.0001) decreased in the expanded phase. In the expanded-team frame (May 2006-2012), there was no mortality, and stroke rates were comparable between the leader and new operator teams: 2.6% vs. 1.2%; P = 0.17. CONCLUSIONS Institutional experience, including instruction on selection of patients and materials best suited for the procedure, is a primary factor driving outcomes of CAS. An effective team-working approach can reliably improve the training of new trainees preserving CAS safety and efficacy.

Safety of Chronic Anticoagulation Therapy After Endovascular Abdominal Aneurysm Repair (EVAR)

OBJECTIVE Current data supporting the effect of anticoagulation drug use on aneurysm sealing and the durability of endovascular abdominal aneurysm repair (EVAR) are conflicting. This study assessed the safety of chronic anticoagulation therapy after EVAR. METHODS Records of 1409 consecutive patients having elective EVAR during 1997-2011 who were prospectively followed were reviewed. Survival, reintervention, conversion, and endoleak rates were analyzed in patients with and without chronic anticoagulants. Cox proportional hazards models were used to estimate the effect of anticoagulation therapy on outcomes. RESULTS One-hundred and three (7.3%) patients were on chronic anticoagulation drugs (80 on vitamin K antagonists) at the time of EVAR. An additional 46 patients started on anticoagulants after repair were identified. Patients on chronic anticoagulation therapy at repair (mean age 73.6 years; 91 males) had more frequent cardiac disease (74.8% vs. 44.2%; p < 00001), but no other differences in demographic and major baseline comorbidities with respect to the others. At baseline, mean abdominal aortic aneurysm (AAA) diameter was 56.43 mm vs. 54.65 mm (p = .076) and aortic neck length 26.54 mm vs. 25.21 mm (p = .26) in patients with and without anticoagulants, respectively. At 5 years, freedom from endoleak rates were 55.5% vs. 69.9% (p < .0001), and freedom from reintervention/conversion rates were 69.4% vs. 82.4% (p < .0001) in patients with (including those with delayed drug use) and without chronic anticoagulants, respectively. Controlling for covariates with the Cox regression method, at a mean follow-up of 64.3 ± 45.2 months after EVAR, use of anticoagulation drugs was independently associated with an increased risk of endoleak (odds ratio, OR 1.6; 95% confidence interval, CI: 1.23-2.07; p < .0001) and reintervention or late conversion rates (OR 1.8; 95% CI: 1.31-2.48; p < .0001). CONCLUSIONS The safety of anticoagulation therapy after EVAR is debatable. Chronic anticoagulation drug use risks exposure to a poor long-term outcome. A critical and balanced decision-making approach should be applied to patients with AAA and cardiac disease who may require prolonged anticoagulation treatment.

A comparative analysis of the outcomes of carotid stenting and carotid endarterectomy in women

OBJECTIVE Randomized controlled trials (RCTs) of carotid endarterectomy (CEA) advised little benefit from surgery in women because of high operative risk. Whether these findings are also applicable to carotid angioplasty and stenting (CAS) is subject of investigation. Our aim was to determine the risk of perioperative and late complications related to CAS and CEA in women. METHODS Data from a single-center carotid surgery database including 1065 individuals with CAS (306 women and 759 men) and 1131 with CEA (325 women and 806 men) were analyzed in a consecutive series of patients. Perioperative risks of death, stroke, and local complications in women undergoing CAS and CEA were compared. Rates of restenosis >50% and stroke at 5 years in symptomatic and asymptomatic women were also assessed. RESULTS The perioperative risks of stroke or death were no different in women who underwent CAS and CEA women (1.9% vs 3.0%; odds ratio [OR] = 0.63; 95% confidence interval [CI], 0.20-1.7; P = .45) whether they were symptomatic or not. Other perioperative complications were also similarly distributed between the two groups of women. Life-table estimates of any periprocedural stroke/death and ipsilateral stroke at 5 years after the procedure did not differ between women with CAS and CEA (4.1% vs 8.1%; P = .18). Five-year rates of restenosis >50% were nonsignificantly higher in women after CEA than after CAS (1.8% vs 8.1%; P = .058). CONCLUSION Women with carotid stenosis might have favorable early and late outcomes from CAS with complication rates similar and even lower than those attained with CEA. CAS, performed by trained operators, may be a valid primary choice for treatment of carotid stenosis, particularly in asymptomatic women for whom the risk of surgery seems to be higher. However, before claiming CAS for women, these results need to be confirmed by large RCTs.