Comparison of prasugrel and clopidogrel used as antiplatelet medication for endovascular treatment of unruptured intracranial aneurysms: A meta-analysis

BACKGROUND: Clopidogrel is routinely used to decrease ischemic complications during neurointerventional procedures. However, the efficacy may be limited by antiplatelet resistance. PURPOSE: Our aim was to analyze the efficacy of prasugrel compared with clopidogrel in the cerebrovascular field. DATA SOURCES: A systematic search of 2 large databases was performed for studies published from 2000 to 2018. STUDY SELECTION: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies reporting treatment-related outcomes of patients undergoing neurointerventional procedures under prasugrel, and studies comparing prasugrel and clopidogrel. DATA ANALYSIS: Random-effects meta-analysis was used to pool the overall rate of complications, ischemic and hemorrhagic events, and influence of the dose of prasugrel. DATA SYNTHESIS: In the 7 included studies, 682 and 672 unruptured intracranial aneurysms were treated under prasugrel (cases) and clopidogrel (controls), respectively. Low-dose (20 mg/5 mg; loading and maintenance doses) prasugrel compared with the standard dose of clopidogrel (300 mg/75 mg) showed a significant reduction in the complication rate (OR 0.36; 95% CI, 0.17–74, P .006; I2 0%). Overall, the ischemic complication rate was significantly higher in the clopidogrel group (40/672 6%; 95% CI, 3%–13%; I2 83% versus 16/682 2%; 95% CI, 1%–5%; I2 73%; P .03). Low and high loading doses of prasugrel were associated with 0.6% (5/535; 95% CI, 0.1%–1.6%; I2 0%) and 9.3% (13/147; 95% CI, 0.2%–18%; I2 60%) intraperiprocedural hemorrhages, respectively (P .001), whereas low and high maintenance doses of prasugrel were associated with 0% (0/433) and 0.9% (2/249; 95% CI, 0.3%–2%; I2 0%) delayed hemorrhagic events, respectively (P .001). LIMITATIONS: Retrospective series and heterogeneous endovascular treatments were limitations. CONCLUSIONS: In our study, low-dose prasugrel compared with clopidogrel premedication was associated with an effective reduction of the ischemic events with an acceptable rate of hemorrhagic complications

Treatment of Intracranial Aneurysms with Self-Expandable Braided Stents: A Systematic Review and Meta-Analysis

International audience; BACKGROUND:The safety and efficacy of treatment with self-expandable braided stents (LEO and LVIS) required further investigation.PURPOSE:Our aim was to analyze the outcomes after treatment with braided stents.DATA SOURCES:A systematic search of 3 databases was performed for studies published from 2006 to 2017.STUDY SELECTION:According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies reporting patients treated with LEO or LVIS stents.DATA ANALYSIS:Random-effects meta-analysis was used to pool the following: aneurysm occlusion rate, complications, and neurologic outcomes.DATA SYNTHESIS:Thirty-five studies evaluating 1426 patients treated with braided stents were included in this meta-analysis. Successful stent delivery and complete aneurysm occlusion were 97% (1041/1095; 95% CI, 95%-98%) (I2 = 44%) and 88.3% (1097/1256; 95% CI, 85%-91%) (I2 = 72%), respectively. Overall, treatment-related complications were 7.4% (107/1317; 95% CI, 5%-9%) (I2 = 44%). Ischemic/thromboembolic events (48/1324 = 2.4%; 95% CI, 1.5%-3.4%) (I2 = 27%) and in-stent thrombosis (35/1324 = 1.5%; 95% CI, 0.6%-1.7%) (I2 = 0%) were the most common complications. Treatment-related morbidity was 1.5% (30/1324; 95% CI, 0.9%-2%) and was comparable between the LEO and LVIS groups. Complication rates between the anterior (29/322 = 8.8%; 95% CI, 3.4%-12%) (I2 = 41%) versus posterior circulation (10/84 = 10.5%; 95% CI, 4%-16%) (I2 = 0%) and distal (30/303 = 8%; 95% CI, 4.5%-12%) (I2 = 48%) versus proximal aneurysms (14/153 = 9%; 95% CI, 3%-13%) (I2 = 46%) were comparable (P > .05).LIMITATIONS:Limitations were selection and publication biases.CONCLUSIONS:In this analysis, treatment with the LEO and LVIS stents was relatively safe and effective. The most common complications were periprocedural thromboembolisms and in-stent thrombosis. The rate of complications was comparable among anterior and posterior circulation aneurysms, as well as for proximal and distally located lesions

Pharmacological Characterization of [3H]CHIBA-3007 Binding to Glycine Transporter 1 in the Rat Brain

Glycine transporter-1 (GlyT-1) in glial cells regulates extracellular levels of glycine, which acts as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptors in the brain. In the present study, we developed a novel radioligand, [3H]3-chloro-N-((S)-((R)-1-methylpiperidin-2-yl)(thiophen- 3-yl)methyl)-4- (trifluoromethyl)picolinamide ([3H]CHIBA-3007), for studying GlyT-1 in the brain. The presence of a single saturable high-affinity binding component for [3H]CHIBA-3007 binding to the rat brain membranes was detected. Scatchard analysis revealed an apparent equilibrium dissociation constant (Kd) of 1.61±0.16 nM and a maximal number of binding sites (Bmax) of 692.8±22.8 fmol/mg protein (mean ± SEM, n = 3). The specific binding of [3H]CHIBA-3007 was inhibited by a number of GlyT-1 inhibitors, such as CHIBA-3007, desmethyl-CHIBA-3007, CHIBA-3008, SSR504734, NFPS/ALX5407, LY2365109 and Org24598, consistent with the pharmacological profiles of GlyT-1 inhibitors. Interestingly, the potency of eight GlyT-1 inhibitors (CHIBA-3007, desmethyl-CHIBA-3007, NFPS/ALX5407, LY2365109, Org24598, SSR504734, sarcosine, and glycine) for blocking in vitro specific binding of [3H]CHIBA-3007 was significantly correlated with the potency of these inhibitors for inhibiting [14C]glycine uptake in the rat brain membranes. In contrast, the GlyT-2 inhibitor ALX1393 exhibited very weak for [3H]CHIBA-3007 binding. Furthermore, the regional distribution of [3H]CHIBA-3007 binding in the rat brain was similar to the previously reported distribution of GlyT-1. The present findings suggest that [3H]CHIBA-3007 would be a useful new radioligand for studying GlyT-1 in the brain

Successful mechanical thrombectomy of acute basilar artery occlusion caused by vertebral artery intimal dysplasia (web)

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Treatment of Middle Cerebral Artery Aneurysms with Flow-Diverter Stents: A Systematic Review and Meta-Analysis

International audienceBACKGROUND: The safety and efficacy of flow-diversion treatment of MCA aneurysms have not been well-established. PURPOSE: Our aim was to evaluate angiographic and clinical outcomes after flow diversions for MCA aneurysms. DATA SOURCES: A systematic search of PubMed, MEDLINE, and Embase was performed for studies published from 2008 to May 2017. STUDY SELECTION: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we selected studies with \textgreater5 patients describing angiographic and clinical outcomes after flow-diversion treatment of MCA aneurysms. DATA ANALYSIS: Random-effects meta-analysis was used to pool the following outcomes: aneurysm occlusion rate, procedure-related complications, rupture rate of treated aneurysms, and occlusion of the jailed branches. DATA SYNTHESIS: Twelve studies evaluating 244 MCA aneurysms were included in this meta-analysis. Complete/near-complete occlusion was obtained in 78.7% (95% CI, 67.8%-89.7%) of aneurysms. The rupture rate of treated aneurysms during follow-up was 0.4% per aneurysm-year. The rate of treatment-related complications was 20.7% (95% CI, 14%-27.5%), and approximately 10% of complications were permanent. The mortality rate was close to 2%. Nearly 10% (95% CI, 4.7%-15.5%) of jailed arteries were occluded during follow-up, whereas 26% (95% CI, 14.4%-37.6%) had slow flow. Rates of symptoms related to occlusion and slow flow were close to 5%. LIMITATIONS: Small and retrospective series could affect the strength of the reported results. CONCLUSIONS: Given the not negligible rate of treatment-related complications, flow diversion for MCA aneurysms should be considered an alternative treatment when traditional treatment methods are not feasible. However, when performed in this select treatment group, high rates of aneurysm occlusion and protection against re-rupture can be achieved

Flow-Diversion Effect of LEO Stents: Aneurysm Occlusion and Flow Remodeling of Covered Side Branches and Perforators

International audienceBACKGROUND AND PURPOSE: Flow diversion with intermediate-porosity stents (braided stents) has been recently reported for distally located small aneurysms. The aim of this study was to evaluate the flow-diversion effect of LEO stents on covered vessels and for aneurysms treated with sole stent-placement therapy. MATERIALS AND METHODS: We retrospectively evaluated the following outcomes: 1) remodeling of covered side branches and perforators (extra-aneurysmal flow remodeling), and 2) the occlusion rate of aneurysms treated with sole stent-placement therapy (intra-aneurysmal flow remodeling). RESULTS: Seventy-six patients with 98 covered vessels were studied. Overall, 89 covered arteries (91%) were normal, 7 showed narrowing (7%), and 2 (2%) were occluded (1 posterior communicating artery and 1 MCA) without related complications (mean DSA follow-up, 14 months). Univariate and multivariate analyses highlighted smoking (P = .03) and the length of follow-up (P = .002) as factors associated with arterial remodeling. Of the 17 Sylvian (lenticulostriate arteries) and 7 basilar perforators, 1 (4%) group of Sylvian perforators covered with double stents had asymptomatic remodeling. Ten aneurysms (mean size, 3.5 mm) were treated with LEO stents as stent monotherapy (5 recanalized after coiling and 5 directly treated with the LEO). Complete occlusion (Raymond-Roy I) was achieved in 70% of aneurysms (mean follow-up, 14 months). The Raymond-Roy I occlusion rate among recanalized aneurysms and those directly treated with LEO stents was 80% and 60%, respectively (P = .9). CONCLUSIONS: The rate of flow remodeling on the covered arteries and perforators was 9% and 4%, respectively, and was clinically irrelevant in all cases. Complete occlusion of aneurysms treated with sole stent-placement therapy was 70%. These data stress the flow-diversion properties of LEO stents

Antiplatelet Therapy in Patients with Aneurysmal SAH: Impact on Delayed Cerebral Ischemia and Clinical Outcome. A Meta-Analysis

International audienceBackground and purpose: Delayed cerebral ischemia strongly impacts clinical outcome after aneurysmal SAH. The effect of antiplatelet therapy on delayed cerebral ischemia has been described with heterogeneous results. Our aim was to analyze the efficacy of antiplatelet therapy on delayed cerebral ischemia and clinical outcome in patients with SAH.Data sources: A systematic search of 3 databases was performed for studies published from 1990 to 2019.Study selection: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies comparing the rates of delayed cerebral ischemia and clinical outcomes among patients with SAH with and without antiplatelet therapy.Data analysis: Random-effects meta-analysis was used to pool the following: delayed cerebral ischemia, mortality, and good outcome rates.Data synthesis: Including 7 studies, 1060 and 1762 patients with SAH were endovascularly or surgically treated with (cases) and without (controls) antiplatelet therapy, respectively. Overall, antiplatelet therapy did not significantly decrease delayed cerebral ischemia rates compared with the control group (219/1060 versus 485/1762, OR = 0.781; 95% CI, 0.46-1.31; P = .33). Among patients treated endovascularly, there was a trend toward lower delayed cerebral ischemia rates after antiplatelet therapy (157/778 versus 413/1410, OR = 0.552; 95% CI, 0.273-1.115; P = .06). Long-term (>2 weeks) antiplatelet therapy tended to be associated with a lower incidence of delayed cerebral ischemia (63/438 versus 96/353, OR = 0.379; 95% CI, 0.12-1.2; P = .06). The good-outcome rate was significantly higher (803/1144 versus 1175/1775, OR = 1.368; 95% CI, 1.117-1.676; P = .002) and the mortality rate was significantly lower (79/672 versus 97/571, OR = 0.656; 95% CI, 0.47-0.91; P = .01) among the antiplatelet therapy group.Limitations: Heterogeneity was high for most outcomes.Conclusions: Overall, the incidence of delayed cerebral ischemia seems not to be significantly reduced among the antiplatelet therapy group. However, delayed cerebral ischemia tended to be lower among subjects with both long-term antiplatelet therapy and endovascular treatment and antiplatelet administration. Poor outcome and mortality rates were significantly reduced among the antiplatelet therapy group

Treatment of unruptured distal anterior circulation aneurysms with flow-diverter stents: A meta-analysis

BACKGROUND: The safety and efficacy of flow diversion among distal anterior circulation aneurysms must be proved. PURPOSE: Our aim was to analyze the outcomes after flow diversion among MCA, anterior communicating artery, and distal anterior cerebral artery aneurysms. DATA SOURCES: A systematic search of 3 databases was performed for studies published from 2005 to 2018. STUDY SELECTION: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies reporting flow diversion of distal anterior circulation aneurysms. DATA ANALYSIS: Random-effects meta-analysis was used to pool aneurysm occlusion and complication rates. From the individual patient data, univariate and multivariate analyses were used to test predictors of occlusion and complications. DATA SYNTHESIS: We included 27 studies (484 aneurysms). The long-term adequate occlusion rate (O’Kelly-Marotta scale, C–D) was 82.7% (295/364; 95% CI, 77.4%– 87.9%; I2 52%). Treatment-related complications were 12.5% (63/410; 95% CI, 9%–16%%; I2 18.8%), with 5.4% (29/418; 95% CI, 3.2%–7.5%; I2 0%) morbidity. MCA location was an independent factor associated with lower occlusion (OR 0.5, P .03) and higher complication rates (OR 1.8, P .02), compared with anterior communicating artery and distal anterior cerebral artery aneurysms. The Pipeline Embolization Device (versus other stents) gave better occlusion rates (OR 2.6, P .002), whereas large/giant aneurysms were associated with higher odds of complications (OR 2.2, P .03). The rates of occlusion and narrowing of arteries covered by flow-diverter stents were 6.3% (29/283; 95% CI, 3.5%–9.1%; I2 4.2%) and 23.8% (69/283; 95% CI, 15.7%–32%; I2 80%), respectively. Symptoms related to occlusion and narrowing of the jailed arteries were 3.5% (6/269; 95% CI, 1.1%–5%; I2 0%) and 3% (6/245; 95% CI, 1%– 4%; I2 0%), respectively. LIMITATIONS: We reviewed small and retrospective series. CONCLUSIONS: Flow diversion among distal anterior circulation aneurysms is effective, leading to adequate aneurysm occlusion in 83% of cases. However, this strategy has some limitations among MCA and larger lesions, especially related to the higher rate of complications. Compared with the other devices, the Pipeline Embolization Device seems to be associated with a higher occlusion rate