Long-term outcomes of stenting and endarterectomy for symptomatic carotid stenosis: a preplanned pooled analysis of individual patient data.

BACKGROUND: The risk of periprocedural stroke or death is higher after carotid artery stenting (CAS) than carotid endarterectomy (CEA) for the treatment of symptomatic carotid stenosis. However, long-term outcomes have not been sufficiently assessed. We sought to combine individual patient-level data from the four major randomised controlled trials of CAS versus CEA for the treatment of symptomatic carotid stenosis to assess long-term outcomes. METHODS: We did a pooled analysis of individual patient-level data, acquired from the four largest randomised controlled trials assessing the relative efficacy of CAS and CEA for treatment of symptomatic carotid stenosis (Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy trial, International Carotid Stenting Study, and Carotid Revascularization Endarterectomy versus Stenting Trial). The risk of ipsilateral stroke was assessed between 121 days and 1, 3, 5, 7, 9, and 10 years after randomisation. The primary outcome was the composite risk of stroke or death within 120 days after randomisation (periprocedural risk) or subsequent ipsilateral stroke up to 10 years after randomisation (postprocedural risk). Analyses were intention-to-treat, with the risk of events calculated using Kaplan-Meier methods and Cox proportional hazards analysis with adjustment for trial. FINDINGS: In the four trials included, 4775 patients were randomly assigned, of whom a total of 4754 (99·6%) patients were followed up for a maximum of 12·4 years. 21 (0·4%) patients immediately withdrew consent after randomisation and were excluded. Median length of follow-up across the studies ranged from 2·0 to 6·9 years. 129 periprocedural and 55 postprocedural outcome events occurred in patients allocated CEA, and 206 and 57 for those allocated CAS. After the periprocedural period, the annual rates of ipsilateral stroke per person-year were similar for the two treatments: 0·60% (95% CI 0·46-0·79) for CEA and 0·64% (0·49-0·83) for CAS. Nonetheless, the periprocedural and postprocedural risks combined favoured CEA, with treatment differences at 1, 3, 5, 7, and 9 years all ranging between 2·8% (1·1-4·4) and 4·1% (2·0-6·3). INTERPRETATION: Outcomes in the postprocedural period after CAS and CEA were similar, suggesting robust clinical durability for both treatments. Although long-term outcomes (periprocedural and postprocedural risks combined) continue to favour CEA, the similarity of the postprocedural rates suggest that improvements in the periprocedural safety of CAS could provide similar outcomes of the two procedures in the future. FUNDING: None

FACTORS ASSOCIATED WITH ADHERENCE TO RECOMMENDATIONS FOR SCREENING MAMMOGRAPHY AMONG AMERICAN INDIAN WOMEN IN COLORADO

Objective: To compare adherence to screening mammography recommendations of American Indian and non-Hispanic White women in the Denver, Colorado, area. Design/Setting/Participants: This study retrospectively examined adherence patterns in 229 American Indian and 60,197 non-Hispanic White women $40 years and older, with at least one screening mammogram in the Colorado Mammography Project (CMAP), from January 1, 1999, to December 31, 2003. The CMAP was a prospective study of women receiving mammograms at participating clinics around Denver. Main Outcome Measures: Using logistic mixed models, we defined two dependent variables as annual and biennial adherence from the intervals between screening mammograms for each woman. Results: Biennial adherence was substantially higher than annual adherence for both American Indian and non-Hispanic White women in our analyses. American Indian women were less likely than non-Hispanic White women to adhere to biennial recommendations in multivariate models controlling for age, family history of breast cancer, and economic status (zip code): odds ratio (OR) .4 and 95% confidence interval (CI) .2–.6. The association between American Indian race/ethnicity and annual adherence was similar, although not as strong (OR .5, 95% CI .3–.8). Conclusions: American Indian women in the CMAP cohort were less likely than non- Hispanic White women to adhere to recommendations for screening mammography, both annually and biennially. Additional research is needed to explore the effect of biennial screening and other barriers among American Indian women

Differential outcomes of carotid stenting and endarterectomy performed exclusively by vascular surgeons in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

ObjectiveOutcomes in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) did not differ between carotid artery stenting (CAS) and carotid endarterectomy (CEA) for the composite primary end point of stroke, myocardial infarction (MI), or death during the periprocedural period or ipsilateral stroke within 4 years. Rigorous credentialing and training of interventionists, including vascular surgeons, were required for the randomization phase of CREST. Because the lead-in phase of CREST had suggested higher perioperative risks after CAS performed by vascular surgeons, the purpose of this analysis was to examine differences in outcomes after randomization between CAS and CEA performed by vascular surgeons.MethodsCREST is a prospective randomized controlled trial with blinded end point adjudication. Vascular surgeons performed 237 (21%) of the CAS procedures and 765 (65%) of the CEA procedures among 2320 patients who received their assigned treatment. Proportional hazards analyses were used to estimate the relative efficacy of CAS vs CEA for the composite primary end point and also for stroke and death.ResultsAmong 2502 randomized patients, 1321 (53%) were symptomatic and 1181 (47%) were asymptomatic. For procedures performed exclusively by vascular surgeons, the primary end point did not differ between CAS and CEA at 4-year follow-up (6.2% vs 5.6%, respectively; hazard ratio [HR], 1.30; 95% confidence interval [CI], 0.70-2.41; P = .41) In this subgroup, the periprocedural stroke and death rates were higher after CAS than CEA for symptomatic patients (6.1% vs 1.3%; P = .01). Asymptomatic patients also had slightly higher stroke and death rates after CAS (2.6% vs 1.1%; P = .20), although this difference did not reach statistical significance. Conversely, cranial nerve injuries (0.0% vs 5.0%; P < .001) were less frequent after CAS than CEA. The MI rates were slightly lower after CAS (1.3% vs 2.6%; P = .24). In performing CAS, vascular surgeons had outcomes for the periprocedural primary end point comparable to the outcomes of all interventionists (HR, 0.99; 95% CI, 0.50-2.00) after adjusting for age, sex, and symptomatic status. Vascular surgeons also had similar results after CEA for the periprocedural primary end point compared with other surgeons (HR, 0.73; 95% CI, 0.42-1.27).ConclusionsWhen performed by surgeons, CAS and CEA have similar net outcomes, although the periprocedural risks vary (lower stroke with CEA and lower MI with CAS). These data suggest that appropriately trained vascular surgeons may safely offer both CEA and CAS for the prevention of stroke. The remarkably low stroke and death rates after CEA performed by vascular surgeons in CREST, particularly among symptomatic patients, represent the best outcomes ever reported after carotid interventions from a randomized controlled trial. ClinicalTrials.gov identifier: NCT0000473

Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and Thrombin Generation in Sickle Cell Patients at Risk for Stroke.

Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD phenotypes, association with stroke risk has not been well described. We hypothesized that serum levels of biomarkers of coagulation activation correlate with high transcranial Doppler ultrasound velocity and decreases with blood transfusion therapy in SCD patients. Stored serum samples from subjects in the Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA and protein multiplexing techniques. 40 subjects from each treatment arm (Standard Care [SC] and Transfusion [Tx]) at three time points--baseline, study exit and one year post-trial and 10 each of age matched children with SCD but normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline, median vWF, TAT and D-dimer levels were significantly higher among STOP subjects than either HbAA or SNTCD. At study exit, median hemoglobin level was significantly higher while median TCD velocity was significantly lower in Tx compared to SC subjects. Median vWF (409.6 vs. 542.9 μg/ml), TAT (24.8 vs. 40.0 ng/ml) and D-dimer (9.2 vs. 19.1 μg/ml) levels were also significantly lower in the Tx compared to the SC group at study exit. Blood levels of biomarkers coagulation activation/thrombin generation correlated positively with TCD velocity and negatively with number of blood transfusions. Biomarkers of coagulation activation/thrombin generation were significantly elevated in children with SCD, at high risk for stroke. Reduction in levels of these biomarkers correlated with reduction in stroke risk (lower TCD velocity), indicating a possible role for hypercoagulation in SCD associated stroke

Effect of Patching on Reducing Restenosis in the Carotid Revascularization Endarterectomy Versus Stenting Trial

Background and purposeThe purpose is to determine whether patching during carotid endarterectomy (CEA) affects the perioperative and long-term risks of restenosis, stroke, death, and myocardial infarction as compared with primary closure.MethodsWe identified all patients who were randomized and underwent CEA in Carotid Revascularization Endarterectomy versus Stenting Trial. CEA patients who received a patch were compared with patients who underwent CEA with primary closure without a patch. We compared periprocedural and 4-year event rates, 2-year restenosis rates, and rates of reoperation between the 2 groups. We further analyzed results by surgeon specialty.ResultsThere were 1151 patients who underwent CEA (753 [65%] with patch and 329 [29%] with primary closure). We excluded 44 patients who underwent eversion CEA and 25 patients missing CEA data (5%). Patch use differed by surgeon specialty: 89% of vascular surgeons, 6% of neurosurgeons, and 76% of thoracic surgeons patched. Comparing patients who received a patch versus those who did not, there was a significant reduction in the 2-year risk of restenosis, and this persisted after adjustment by surgeon specialty (hazard ratio, 0.35; 95% confidence interval, 0.16-0.74; P=0.006). There were no significant differences in the rates of periprocedural stroke and death (hazard ratio, 1.58; 95% confidence interval, 0.33-7.58; P=0.57), in immediate reoperation (hazard ratio, 0.6; 95% confidence interval, 0.16-2.27; P=0.45), or in the 4-year risk of ipsilateral stroke (hazard ratio, 1.23; 95% confidence interval, 0.42-3.63; P=0.71).ConclusionsPatch closure in CEA is associated with reduction in restenosis although it is not associated with improved clinical outcomes. Thus, more widespread use of patching should be considered to improve long-term durability.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00004732