Concept: Carotid endarterectomy
Background Previous clinical trials have suggested that carotid-artery stenting with a device to capture and remove emboli (“embolic protection”) is an effective alternative to carotid endarterectomy in patients at average or high risk for surgical complications. Methods In this trial, we compared carotid-artery stenting with embolic protection and carotid endarterectomy in patients 79 years of age or younger who had severe carotid stenosis and were asymptomatic (i.e., had not had a stroke, transient ischemic attack, or amaurosis fugax in the 180 days before enrollment) and were not considered to be at high risk for surgical complications. The trial was designed to enroll 1658 patients but was halted early, after 1453 patients underwent randomization, because of slow enrollment. Patients were followed for up to 5 years. The primary composite end point of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year was tested at a noninferiority margin of 3 percentage points. Results Stenting was noninferior to endarterectomy with regard to the primary composite end point (event rate, 3.8% and 3.4%, respectively; P=0.01 for noninferiority). The rate of stroke or death within 30 days was 2.9% in the stenting group and 1.7% in the endarterectomy group (P=0.33). From 30 days to 5 years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stenting group and 97.3% in the endarterectomy group (P=0.51), and the overall survival rates were 87.1% and 89.4%, respectively (P=0.21). The cumulative 5-year rate of stroke-free survival was 93.1% in the stenting group and 94.7% in the endarterectomy group (P=0.44). Conclusions In this trial involving asymptomatic patients with severe carotid stenosis who were not at high risk for surgical complications, stenting was noninferior to endarterectomy with regard to the rate of the primary composite end point at 1 year. In analyses that included up to 5 years of follow-up, there were no significant differences between the study groups in the rates of non-procedure-related stroke, all stroke, and survival. (Funded by Abbott Vascular; ACT I ClinicalTrials.gov number, NCT00106938 .).
Important data from two large, randomized trials comparing early and late outcomes after carotid endarterectomy and carotid-artery stenting have now been published in the Journal.(1),(2) In common with every other large, multicenter, randomized trial to date, the Asymptomatic Carotid Trial (ACT I) and the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) showed that after the perioperative period, there was no difference in the rate of late ipsilateral stroke after endarterectomy or stenting. In ACT I, which included asymptomatic patients who were deemed to be at average risk, the 5-year rate of ipsilateral stroke (excluding the perioperative period) was . . .
OBJECTIVE: The Centers for Medicaid and Medicare Services (CMS) require high-risk (HR) criteria for carotid artery stenting (CAS) reimbursement. The impact of these criteria on outcomes after carotid endarterectomy (CEA) and CAS remains uncertain. Additionally, if these HR criteria are associated with more adverse events after CAS, then existing comparative effectiveness analysis of CEA vs CAS may be biased. We sought to elucidate this using data from the SVS Vascular Registry. METHODS: We analyzed 10,107 patients undergoing CEA (6370) and CAS (3737), stratified by CMS HR criteria. The primary endpoint was composite death, stroke, and myocardial infarction (MI) (major adverse cardiovascular event [MACE]) at 30 days. We compared baseline characteristics and outcomes using univariate and multivariable analyses. RESULTS: CAS patients were more likely to have preoperative stroke (26% vs 21%) or transient ischemic attack (23% vs 19%) than CEA. Although age ≥80 years was similar, CAS patients were more likely to have all other HR criteria. For CEA, HR patients had higher MACEs than normal risk in both symptomatic (7.3% vs 4.6%; P < .01) and asymptomatic patients (5% vs 2.2%; P < .0001). For CAS, HR status was not associated with a significant increase in MACE for symptomatic (9.1% vs 6.2%; P = .24) or asymptomatic patients (5.4% vs 4.2%; P = .61). All CAS patients had MACE rates similar to HR CEA. After multivariable risk adjustment, CAS had higher rates than CEA for MACE (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.5), death (OR, 1.5; 95% CI, 1.0-2.2), and stroke (OR, 1.3; 95% CI,1.0-1.7), whereas there was no difference in MI (OR, 0.8; 95% CI, 0.6-1.3). Among CEA patients, age ≥80 (OR, 1.4; 95% CI, 1.02-1.8), congestive heart failure (OR, 1.7; 95% CI, 1.03-2.8), EF <30% (OR, 3.5; 95% CI, 1.6-7.7), angina (OR, 3.9; 95% CI, 1.6-9.9), contralateral occlusion (OR, 3.2; 95% CI, 2.1-4.7), and high anatomic lesion (OR, 2.7; 95% CI, 1.33-5.6) predicted MACE. Among CAS patients, recent MI (OR, 3.2; 95% CI, 1.5-7.0) was predictive, and radiation (OR, 0.6; 95% CI, 0.4-0.8) and restenosis (OR, 0.5; 95% CI, 0.3-0.96) were protective for MACE. CONCLUSIONS: Although CMS HR criteria can successfully discriminate a group of patients at HR for adverse events after CEA, certain CMS HR criteria are more important than others. However, CEA appears safer for the majority of patients with carotid disease. Among patients undergoing CAS, non-HR status may be limited to restenosis and radiation.
Introduction Full-length osteopontin (OPN-FL), whose levels are elevated in association with atherosclerosis, is cleaved by thrombin, resulting in the formation of a putatively biologically-active N-terminal cleavage product (OPN-N). This study addresses the hypothesis that statin and antiplatelet therapy in hypertensive patients specifically reduces OPN-N, rather than OPN-FL, in carotid plaques. Methods Seventy-four carotid plaques were collected from patients who underwent carotid endarterectomy (CEA). Plaque tissue was used to measure OPN proteins and for histological and immunohistochemical characterization. Results There were 22 statin-negative and 52 statin-treated patients. In the carotid plaque, immunohistochemical staining for macrophages was higher in statin-negative vs statin-treated patients (high CD68 immunostaining was in 61.9 vs 28.6%, p=.03, respectively). OPN-FL staining had a similar trend, but without statistical significance (78.7 vs 47.8%, p=.08, respectively). Western blot analysis of plaque OPN-FL showed that statin treatment was not associated with significant alteration of its abundance, but with a significantly lower plaque content of OPN-N [median 0.08 (IQR 0.05-1.01) vs 0.81 (IQR 0.27-2.86), respectively, p=.015]. Comparable pattern of association between OPN proteins and antiplatelet therapy was found: the abundance of OPN-FL was not different in plaques from untreated or treated patients, while the abundance of OPN-N was significantly reduced in antiplatelet treated vs non-treated patients [0.08, (IQR 0.05-0.66) vs 0.89, (IQR 0.13-1.94), p=0.004]. Conclusion The effect of anti-atherosclerotic treatment on carotid plaques of hypertensive patients more readily associates with OPN-N than with OPN-FL expression, suggesting that anti-atherosclerotic treatment including statins and antiplatelet drugs modulates the “OPN system”.
The risk of stroke after cardiac and carotid surgery is well established. In contrast, stroke risk in association with non-cardiac and non-carotid surgery and its time course are insufficiently known. We investigated the prevalence of recent and planned surgery among patients with stroke and transient ischemic attack (TIA), time dependency of stroke risk, stroke etiology, and interruption of antithrombotic medication in association with surgery.
Techniques to stratify subgroups of patients with asymptomatic carotid artery disease are urgently needed to guide decisions on optimal treatment. Reliance on estimates of % luminal stenosis has not been effective, perhaps because that approach entirely disregards potentially important information on the pathological process in the wall of the artery.
The UK National Institute for Health and Care Excellence (NICE) guidelines state that carotid endarterectomy should be scheduled within 2 weeks of symptoms. The recent National Stroke Strategy has reduced the time interval to 48 h. This study aimed to review the possible delays.
Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy.
Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis.
Patients with diabetes are at higher risk of developing carotid artery stenosis and resultant stroke. Arachidonoyl phospholipids affect plaque inflammation and vulnerability, but whether diabetic patients have unique carotid artery phospholipidomic profiles is unknown. We performed a comprehensive paired analysis of phospholipids in extracranial carotid endarterectomy (CEA) plaques of matched diabetic and nondiabetic patients and analyzed mass spectrometry-derived profiles of three phospholipids - plasmenyl-phosphatidylethanolamine (pPE), phosphatidylserine (PS), and phosphatidylinositol (PI) - in minimally diseased (MIN) and maximally diseased (MAX) CEA segments. We also measured levels of arachidonic acid (AA), produced by pPE hydrolysis, and choline ethanolamine phosphotransferase 1 (CEPT1), responsible for most pPE de novo biosynthesis. In paired analysis, MIN CEA segments had higher levels than MAX segments of pPE (p < 0.001), PS (p < 0.001), and PI (p < 0.03). MIN diabetic plaques contained higher levels than MAX diabetic plaques of arachidonoyl pPE38:4 and pPE38:5, and CEPT1 was upregulated in diabetic versus nondiabetic plaques. AA levels were relatively greater in MIN versus MAX segments of all CEA segments, and were higher in diabetic than nondiabetic plaques. Our findings suggest that arachidonoyl phospholipids are more likely to be abundant in the extracranial carotid artery plaque of diabetic than nondiabetic patients.