Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2.

BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

Mechanical Thrombectomy of Distal Occlusions in the Anterior Cerebral Artery: Recanalization Rates, Periprocedural Complications, and Clinical Outcome.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke in the anterior circulation are at risk for either primary or, following mechanical thrombectomy, secondary occlusion of the anterior cerebral artery. Because previous studies had only a limited informative value, we report our data concerning the frequency and location of distal anterior cerebral artery occlusions, recanalization rates, periprocedural complications, and clinical outcome. MATERIALS AND METHODS: We performed a retrospective analysis of prospectively collected data of patients with acute ischemic stroke undergoing mechanical thrombectomy in the anterior circulation between June 2010 and April 2015. RESULTS: Of 368 patients included in this analysis, we identified 30 (8.1%) with either primary (n = 17, 4.6%) or secondary (n = 13, 3.5%) embolic occlusion of the distal anterior cerebral artery. The recanalization rate after placement of a stent retriever was 88%. Periprocedural complications were rare and included vasospasms (n = 3, 10%) and dissection (n = 1, 3.3%). However, 16 (53.5%) patients sustained an (at least partial) infarction of the anterior cerebral artery territory. Ninety days after the ictus, clinical outcome according to the modified Rankin Scale score was the following: 0-2, n = 11 (36.6%); 3-4, n = 9 (30%); 5-6, n = 10 (33.3%). CONCLUSIONS: Occlusions of the distal anterior cerebral artery affect approximately 8% of patients with acute ischemic stroke in the anterior circulation receiving mechanical thrombectomy. Despite a high recanalization rate and a low complication rate, subsequent (partial) infarction in the anterior cerebral artery territory occurs in approximately half of patients. Fortunately, clinical outcome appears not to be predominately unfavorable.

Statins reduce peri-procedural complications in carotid stenting.

BACKGROUND: In primary and secondary prevention, statins significantly reduce cardiovascular and cerebrovascular events. Pre-interventional statin medication shows a benefit in carotid artery stenosis patients treated with endarterectomy; however, there are few data available for patients treated with stent-angioplasty. The aim of this study was to investigate whether pre-interventional statin therapy is associated with decreased peri-interventional risk of stroke, myocardial infarction, and mortality in patients undergoing stent-angioplasty for internal carotid stenosis. METHODS: Data for 344 consecutively documented patients with internal carotid artery stenosis treated with stent-angioplasty in the years 2002-2012 at the same stroke center were collected in a prospectively defined database. Risk factors, medication, and indication for therapy were documented. Univariate and multivariate analysis was performed to investigate independent reduction of peri-interventional stroke, myocardial infarction, or death by statin medication prior to stent-angioplasty. RESULTS: The median age was 70 years (p25: 63, p75: 76), 75.5% of patients were male, and the median stenosis was 85% according to ECST criteria (p25: 80%, p75: 90%). 20.1% of patients had asymptomatic stenoses, and 60.2% had statin medication before stenting. As per multivariate analysis, pre-interventional statin medication was a predictor for significant peri-interventional risk reduction regarding primary endpoint ischemic stroke, myocardial infarction (MI), or death (odds ratio (OR) 0.31, p = .006). Statins also had a significant protective effect in secondary endpoint ischemic stroke, intracranial bleeding or death (OR 0.39, p = .014), and ischemic stroke or myocardial infarction (OR 0.20; p = .002). CONCLUSIONS: This study shows that pre-interventional statin medication has a protective effect against peri-interventional stroke, MI, or death in patients with internal carotid artery stenosis treated with stent-angioplasty. Accordingly, statins could be considered as a standard pre-interventional medical therapy in carotid stenting.

Carotid stenting: is there an operator effect? A pooled analysis from the carotid stenting trialists' collaboration.

BACKGROUND AND PURPOSE: Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists' Collaboration database. METHODS: The Carotid Stenting Trialists' Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol. RESULTS: Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36-3.87]) and intermediate annual in-trial volumes (3.2-5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14-3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%). CONCLUSIONS: Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year.

Recanalization with stent-retriever devices in patients with wake-up stroke.

BACKGROUND AND PURPOSE: Stent-retriever devices play an increasing role in the interventional treatment of acute stroke patients, because fast recanalization can be achieved. The purpose of this study was to evaluate the feasibility of stent-retriever recanalization in patients with wake-up stroke in the anterior circulation. MATERIALS AND METHODS: We retrospectively analyzed clinical and angiographic data of 19 consecutive patients with wake-up stroke who were treated with stent-retriever devices between 2009 and October 2011. Recanalization was assessed by using the Thrombolysis in Cerebral Infarction score. Clinical outcome was evaluated at discharge and after 90 days by using the modified Rankin Scale. RESULTS: Median NIHSS score at admission was 17 (IQR, 15-20). Before the procedure, the TICI score was 0 in 18 patients and 1 in 1 patient. Recanalization with stent-retriever devices was successful (TICI ≥ 2) in 94.7%. Mean time to flow restoration was 36.7 minutes and to complete recanalization 83.7 minutes. Symptomatic intracranial hemorrhage occurred in 4 patients (21.1%). Eight patients had an NIHSS improvement of ≥4 points between admission and discharge. After 90 days, 2 (10.5%) of our patients presented with mRS 0-2; seven (36.8%) died. CONCLUSIONS: Despite successful and rapid recanalization with stent-retriever devices, good clinical outcome in patients with wake-up stroke is achieved in a minority of patients. Clinical outcome remains poor. Bleeding rates were higher compared with recanalization procedures within 6 hours after stroke onset.

[Stent and surgery for symptomatic carotid stenosis. SPACE study results]. / Stent oder Operation bei symptomatischer Karotisstenose. Ergebnisse der SPACE-Studie.

The SPACE trial compared risk and effectiveness of stent-supported angioplasty (CAS) vs carotid endarterectomy (CEA) using a noninferiority design in patients with symptomatic stenoses. Intention-to-treat analysis of the entire study population of 1,214 patients showed that primary endpoint events (ipsilateral stroke or death between randomisation and day 30) occurred in 6.92% of the CAS group and 6.45% of the CEA group. The 95% confidence interval (CI) of the absolute risk difference ranged from -1.94% to +2.87%, therefore the noninferiority was not proven. The same was true for the analysis of protocols. No significant differences between the two treatment methods were found in primary or any of the secondary endpoints. There were also no differences in short-term prevention. The endpoint 'ipsilateral ischemic stroke or vascular death between randomisation and 6 months' occurred in 7.4% of the CAS and 6.5% of the CEA patients (odds ratio 1.16, 95% confidence interval 0.74-1.82). Instent restenoses were significantly more common in the CAS group (4.6% vs 2.2%, odds ratio 2.14, 95% CI 1.10-4.18). Surgery remains the gold standard in treatment of patients with symptomatic carotid artery stenosis. Stent-supported angioplasty can be an alternative only in the hands of an experienced interventionalist with proven low periprocedural complication rate.

Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery.

BACKGROUND: After coronary artery bypass surgery, patients have a high cumulative rate of graft closure and recurrent ischemic events. We sought to determine whether antiplatelet therapy with clopidogrel would be more effective than aspirin, the accepted standard, in these patients. METHODS AND RESULTS: The event rates for all-cause mortality, vascular death, myocardial infarction, stroke, and rehospitalization were determined for the 1480 patients with a history of cardiac surgery randomized to either clopidogrel or aspirin in a trial of 19 185 patients. The event rate per year of vascular death, myocardial infarction, stroke, or rehospitalization was 22.3% in the 705 patients randomized to aspirin and 15.9% in the 775 patients randomized to clopidogrel (P:=0.001). A risk reduction was also seen in each of the individual end points examined, including a 42.8% relative risk reduction in vascular death in patients on clopidogrel versus aspirin (P:=0.030). In a multivariate model incorporating baseline clinical characteristics, clopidogrel therapy was independently associated with a decrease in vascular death, myocardial infarction, stroke, or rehospitalization in patients with a history of cardiac surgery, with a 31.2% relative risk reduction (95% CI, 15.8 to 43.8; P:=0.0003). Although clopidogrel therapy was efficacious in the entire Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) population, multivariate analysis demonstrated that patients with previous cardiac surgery derived particular benefit (P:=0.015). CONCLUSION: Compared with aspirin, clopidogrel therapy results in a striking reduction in the elevated risk for recurrent ischemic events seen in patients with a history of prior cardiac surgery, along with a decreased risk of bleeding.