Summary Background Age was reported to be an effect-modifier in four randomised controlled trials comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA), with better CEA outcomes ...than CAS outcomes noted in the more elderly patients. We aimed to describe the association of age with treatment differences in symptomatic patients and provide age-specific estimates of the risk of stroke and death within narrow (5 year) age groups. Methods In this meta-analysis, we analysed individual patient-level data from four randomised controlled trials within the Carotid Stenosis Trialists' Collaboration (CSTC) involving patients with symptomatic carotid stenosis. We included only trials that randomly assigned patients to CAS or CEA and only patients with symptomatic stenosis. We assessed rates of stroke or death in 5-year age groups in the periprocedural period (between randomisation and 120 days) and ipsilateral stroke during long-term follow-up for patients assigned to CAS or CEA. We also assessed differences between CAS and CEA. All analyses were done on an intention-to-treat basis. Findings Collectively, 4754 patients were randomly assigned to either CEA or CAS treatment in the four studies. 433 events occurred over a median follow-up of 2·7 years. For patients assigned to CAS, the periprocedural hazard ratio (HR) for stroke and death in patients aged 65–69 years compared with patients younger than 60 years was 2·16 (95% CI 1·13–4·13), with HRs of roughly 4·0 for patients aged 70 years or older. We noted no evidence of an increased periprocedural risk by age group in the CEA group (p=0·34). These changes underpinned a CAS-versus CEA periprocedural HR of 1·61 (95% CI 0·90–2·88) for patients aged 65–69 years and an HR of 2·09 (1·32–3·32) for patients aged 70–74 years. Age was not associated with the postprocedural stroke risk either within treatment group (p≥0·09 for CAS and 0·83 for CEA), or between treatment groups (p=0·84). Interpretation In these RCTs, CEA was clearly superior to CAS in patients aged 70–74 years and older. The difference in older patients was almost wholly attributable to increasing periprocedural stroke risk in patients treated with CAS. Age had little effect on CEA periprocedural risk or on postprocedural risk after either procedure. Funding None.
Summary Background In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural ...period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. Methods Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov , number NCT00004732. Findings 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio HR 0·90, 95% CI 0·63–1·29; p=0·58). Female sex (1·79, 1·25–2·56), diabetes (2·31, 1·61–3·31), and dyslipidaemia (2·07, 1·01–4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34–3·77) but not after carotid artery stenting (0·77, 0·41–1·42). Interpretation Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation. Funding National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.
Rationale
Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in ...medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization.
Aim
Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis.
Methods and design
CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg.
Study outcomes
The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes.
Sample size
Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm.
Discussion
Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested.
Trial registration
United States National Institutes of Health Clinicaltrials.gov NCT02089217
BACKGROUND—Sustained benefits of drug-eluting stents in femoropopliteal arteries have not been demonstrated. This prospective, multinational, randomized study was designed to compare the 12-month ...safety and effectiveness of a polymer-free, paclitaxel-coated nitinol drug-eluting stent (DES) with percutaneous transluminal angioplasty (PTA) and provisional bare metal stent (BMS) placement in patients with femoropopliteal peripheral artery disease.
METHODS AND RESULTS—Patients were randomly assigned to primary DES implantation (n=236) or PTA (n=238). Demographics and lesion characteristics were similar between groups (eg, average lesion length, approximately 65±40 mm). One hundred twenty patients had acute PTA failure and underwent secondary random assignment to provisional DES (n=61) or BMS (n=59). Primary end points were the 12-month rates of event-free survival and patency in the primary DES and PTA groups. Compared with the PTA group, the primary DES group exhibited superior 12-month event-free survival (90.4% versus 82.6%; P=0.004) and primary patency (83.1% versus 32.8%; P<0.001), satisfying the primary hypotheses. In the secondary evaluations, (1) the primary DES group exhibited superior clinical benefit compared with the PTA group (88.3% versus 75.8%; P<0.001), (2) the provisional DES group exhibited superior primary patency (89.9% versus 73.0%; P=0.01) and superior clinical benefit (90.5% and 72.3%, P=0.009) compared with the provisional BMS group, and (3) the stent fracture rate (both DES and BMS) was 0.9% (4/457).
CONCLUSIONS—Femoropopliteal peripheral artery disease treatment with the paclitaxel-eluting stent was associated with superior 12-month outcomes compared with PTA and provisional BMS placement.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT00120406.
Objective The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated a higher periprocedural stroke and death (S+D) rate among patients randomized to carotid artery ...stenting (CAS) than to carotid endarterectomy (CEA). Herein, we seek factors that affect the CAS-CEA treatment differences and potentially to identify a subgroup of patients for whom CAS and CEA have equivalent periprocedural S+D risk. Methods Patient and arterial characteristics were assessed as effect modifiers of the CAS-CEA treatment difference in 2502 patients by the addition of factor-by-treatment interaction terms to a logistic regression model. Results Lesion length and lesions that were contiguous or were sequential and noncontiguous extending remote from the bulb were identified as influencing the CAS-to-CEA S+D treatment difference. For those with longer lesion length (≥12.85 mm), the risk of CAS was higher than that of CEA (odds ratio OR, 3.42; 95% confidence interval CI, 1.19-9.78). Among patients with sequential or remote lesions extending beyond the bulb, the risk for S+D was higher for CAS relative to CEA (OR, 9.01; 95% CI, 1.20-67.8). For the 37% of patients with lesions that were both short and contiguous, the odds of S+D in those treated with CAS was nonsignificantly 28% lower than for CEA (OR, 0.72; 95% CI, 0.21-2.46). Conclusions The higher S+D risk for those treated with CAS appears to be largely isolated to those with longer lesion length and/or those with sequential and remote lesions. In the absence of those lesion characteristics, CAS appears to be as safe as CEA with regard to periprocedural risk of S+D.
In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, ...myocardial infarction, or death (7.2% and 6.8%, respectively; P=0.51). Stroke was more common with carotid-artery stenting than carotid endarterectomy; myocardial infarction was more common with carotid endarterectomy. The 4-year rate of stroke or death was 6.4% for carotid-artery stenting and 4.7% for carotid endarterectomy (P=0.03).
In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, myocardial infarction, or death (7.2% and 6.8%, respectively).
Carotid-artery atherosclerosis is an important cause of ischemic stroke.
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Carotid endarterectomy has been established as effective treatment for both symptomatic patients and asymptomatic patients.
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Carotid-artery stenting is another option for treatment. The results of randomized trials comparing carotid-artery stenting and carotid endarterectomy for use in symptomatic patients are conflicting.
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The primary aim of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) was to compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis.
Methods
Study Design
CREST is a randomized, controlled trial with blinded end-point adjudication. Ethics review . . .
Asymptomatic carotid stenosis is the most frequent indication for carotid endarterectomy (CEA) in the United States. Published trials and guidelines support CEA indications in selected patients with ...longer projected survival and when periprocedural complications are low. Transfemoral carotid artery stenting with embolic protection (CAS) is a newer treatment option. The objective of this study was to compare outcomes in asymptomatic, nonoctogenarian patients treated with CAS vs CEA.
Patient-level data was analyzed from 2544 subjects with ≥70% asymptomatic carotid stenosis who were randomized to CAS or CEA in addition to standard medical therapy. One trial enrolled 1091 (548 CAS, 543 CEA) and another enrolled 1453 (1089 CAS, 364 CEA) asymptomatic patients less than 80 years old (upper age eligibility). Independent neurologic assessment and routine cardiac enzyme screening were performed. The prespecified, primary composite endpoint was any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years after randomization.
There was no significant difference in the primary endpoint between CAS and CEA (5.3% vs 5.1%; hazard ratio, 1.02; 95% confidence interval, 0.7-1.5; P = .91). Periprocedural rates for the components are (CAS vs CEA): any stroke (2.7% vs 1.5%; P = .07), myocardial infarction (0.6% vs 1.7%; P = .01), death (0.1% vs 0.2%; P = .62), and any stroke or death (2.7% vs 1.6%; P = .07). After this period, the rates of ipsilateral stroke were similar (2.3% vs 2.2%; P = .97).
In a pooled analysis of two large randomized trials of CAS and CEA in asymptomatic, nonoctogenarian patients, CAS achieves comparable short- and long-term results to CEA.
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