Comparison of drug-coated balloon angioplasty versus standard medical therapy on recurrent stroke and mortality rates among patients with symptomatic intracranial atherosclerotic stenosis: protocol for a systematic review and meta-analysis.

INTRODUCTION: Stroke remains the second leading cause of death worldwide, a common cause of which is intracranial atherosclerotic stenosis (ICAS). Medical treatment is recommended as first-line therapy for treating ICAS, but the recurrence rate remains high. Drug-coated balloon (DCB) angioplasty has been designed to lower the risk of recurrent stenosis, holding therapeutic promise in the treatment of ICAS. However, the benefits of DCB require further evaluation. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols was followed to develop this protocol. We will systematically search online databases including Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China Biological Medicine Database, ClinicalTrials.gov and WHO ICTRP from 1 January 2011 to the date of search. This will be supplemented by a manual search of unpublished and ongoing trials to manually select articles for inclusion. Inclusion criteria are randomised or quasi-randomised clinical trials and observational studies that investigated DCB or medical treatment for patients with a symptomatic ICAS of 50%-99%. The primary outcome is short-term composite safety including death of any cause, or non-fatal stroke. Secondary outcomes include long-term death or stroke, restenosis, neurological rehabilitation, quality of life and other complications. The available data will be analysed using meta-analysis, if appropriate. The evaluation of heterogeneity and biases will be guided by the Cochrane Handbook for Systematic Reviews of Interventions. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval as all available data from eligible studies will be anonymous with no concerns regarding privacy. Our findings will be disseminated through international conferences and peer-reviewed publications. Additional data from the study are available on request to corresponding authors via email. PROSPERO REGISTRATION NUMBER: CRD42022341607.

Clinical evidence in ischemic stroke: Where we have gone so far and hopes for the future.

OBJECTIVE: Ischemic stroke is a significant cause of disability and death worldwide. Randomized clinical trials (RCTs) are important in changing guidelines and treatment strategies. This study aimed to analyze the progress of RCTs in ischemic stroke and to guide future research directions. METHODS: Ischemic stroke-related RCT articles were identified in six high-impact medical journals using the Web of Science Core Collection database. Google Scholar was used to check whether relevant articles were included in the guidelines. The characteristics of these articles were analyzed and future research hotspots were predicted. RESULTS: 389 relevant articles were included in the analysis. The number of articles increased rapidly from 1972 to 2022, from 5 (1.3%; 1972-1982) to 208 (53.5%; 2013-2022) articles. 338 (86.9%) articles were included in relevant guidelines. According to corresponding author location, Europe was the source of the highest number of publications (183; 47.0%), followed by the Americas (152; 39.1%) and the Western Pacific (54; 13.9%). The number of publications steadily increased over time in the USA, England, Canada, Australia, Germany, and France, and surged in China and Spain, especially in the last 5 years. In recent years, endovascular therapy has accounted for the majority of ischemic stroke-related RCT articles. CONCLUSIONS: Numerous RCTs related to ischemic stroke have been conducted in recent decades, and both the number of articles and their contribution to guideline updates are increasing. Also, a shift in research topics was observed. However, great regional imbalances in this research exist, calling for more research to be conducted in specific regions to promote the generalizability of trial conclusions.

Correlations between intravascular pressure gradients and cerebral blood flow in patients with symptomatic, medically refractory, anterior circulation artery stenosis: an exploratory study.

BACKGROUND: Fractional flow reserve is widely used in coronary disease management, with a threshold of 0.80. However, similar thresholds are unclear in functional assessment of intracranial atherosclerotic stenosis (ICAS). OBJECTIVE: To investigate the potential threshold values in functional assessment of ICAS by studying the relation between pressure-derived indexes and perfusion parameters derived from arterial spin labeling (ASL). METHODS: Patients were consecutively screened between June 2019 and December 2020. The translesional gradient indices were measured by pressure guidewire under resting-state conditions and recorded as mean distal/proximal pressure ratios (Pd/Pa) and translesional pressure difference (Pa-Pd). Preoperative and postoperative cerebral blood flow (CBF) bilaterally and the relative cerebral blood flow ratio (rCBF) were measured and recorded by ASL imaging. Patients were defined as having reversible hemodynamic insufficiency only if the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Preoperative and postoperative Pd/Pa or Pa-Pd values of those patients were used to calculate the threshold. RESULTS: Twenty-five patients (19 men, 6 women) with a mean age of 56.7±9.4 years were analyzed. Seventeen patients (68%) had lesions at the M1 segment of the middle cerebral artery, eight patients (32%) had lesions in the intracranial internal carotid artery. In 14 of the 25 patients, the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Cut-off values of Pd/Pa=0.81 and Pa-Pd=8 mm Hg were suggested to be associated with hemodynamic insufficiency. CONCLUSIONS: In a highly selected subgroup with ICAS, cut-off values of translesional pressure gradients (Pd/Pa=0.81 or Pa-Pd=8 mm Hg) were preliminarily established, which may facilitate clinical decision-making in the management of ICAS.

Transcarotid versus transfemoral access for cerebrovascular intervention: protocol for a systematic review and meta-analysis.

INTRODUCTION: Cerebrovascular intervention is an excellent option to treat cerebrovascular diseases. Interventional access is a prerequisite and a foundation for cerebrovascular intervention, which is crucial to the success of an intervention. Although transfemoral arterial access (TFA) has become a popular and acceptable method of access for cerebrovascular angiography and intervention in clinical practice, it has some drawbacks that limit the usage in cerebrovascular interventions. Therefore, transcarotid arterial access (TCA) has been developed in cerebrovascular interventions. We aim to conduct a systematic review to compare the safety and efficacy of TCA with TFA for cerebrovascular intervention. METHODS AND ANALYSIS: In this protocol, Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols were followed. PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials will be searched mainly from 1 January 2004, to the formal search date. Additionally, reference lists and clinical trial registries will be searched. We will include clinical trials with more than 30 participants, which reported the endpoints of stroke, death and myocardial infarction. Two investigators will independently select studies, extract data and assess bias risk. A standardised mean difference with 95% CI will be presented for continuous data, and a risk ratio with 95% CI will be presented for dichotomous data. On inclusion of sufficient studies, subgroup analysis and sensitivity analysis will be conducted. The funnel plot and Egger's test will be used to assess publication bias. ETHICS AND DISSEMINATION: As only published sources will be used in this review, ethical approval is not required. We will publish the results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022316468.

Stenting versus medical therapy alone for symptomatic intracranial arterial stenosis: protocol for a systematic review and individual patient data meta-analysis.

INTRODUCTION: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. However, whether the treatment options for symptomatic ICAS is stent placement or medical therapy alone is still controversial. At present, three multicentre randomised controlled trials (RCTs) have been published, but their research designs are also slightly different and the conclusions are not completely consistent. Therefore, we plan to conduct a systematic review and individual patient data (IPD) meta-analysis of randomised clinical trials to ascertain safety and efficacy of stenting versus medical therapy alone for symptomatic patients with intracranial arterial stenosis. METHODS AND ANALYSES: We will identify RCTs comparing stenting vs medical therapy alone in patients with symptomatic ICAS stenosis (70%-99%) through a systematic search, mainly including PubMed, MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.gov. Individual-level patient data for a prespecified list of variables will be sought from authors of all eligible studies. The primary outcome was a composite of stroke or death within 30 days, or stroke in territory of qualifying artery beyond 30 days after randomisation. IPD meta-analysis will be conducted with a one-stage approach. ETHICS AND DISSEMINATION: Ethical approval and individual patient consent will not be required in most cases since this IPD meta-analysis will use pseudoanonymised data from RCTs. Results will be disseminated through peer-reviewed journals and international conferences. PROSPERO REGISTRATION NUMBER: CRD42022369922.

Different types of percutaneous endovascular interventions for acute ischemic stroke.

BACKGROUND: Acute ischemic stroke (AIS) is the abrupt reduction of blood flow to a certain area of the brain which causes neurologic dysfunction. Different types of percutaneous arterial endovascular interventions have been developed, but as yet there is no consensus on the optimal therapy for people with AIS. OBJECTIVES: To compare the safety and efficacy of different types of percutaneous arterial endovascular interventions for treating people with AIS. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4 of 12, 2022), MEDLINE Ovid (1946 to 13 May 2022), Embase (1947 to 15 May 2022), Science Citation Index Web of Science (1900 to 15 May 2022), Scopus (1960 to 15 May 2022), and China Biological Medicine Database (CBM; 1978 to 16 May 2022). We also searched the ClinicalTrials.gov trials register and the World Health Organization (WHO) International Clinical Trials Registry Platform to 16 May 2022. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing one percutaneous arterial endovascular intervention with another in treating adult patients who have a clinical diagnosis of AIS due to large vessel occlusion and confirmed by imaging evidence, including thrombo-aspiration, stent-retrieval thrombectomy, aspiration-retriever combined technique, and thrombus mechanical fragmentation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the literature searches, identified eligible trials, and extracted data. A third review author participated in discussions to reach consensus decisions when any disputes occurred. We assessed risk of bias and applied the GRADE approach to evaluate the quality of the evidence. The primary outcome was rate of modified Rankin Scale (mRS) of 0 to 2 at three months. Secondary outcomes included the rate of modified Thrombolysis In Cerebral Infarction (mTICI) of 2b to 3 postprocedure, all-cause mortality within three months, rate of intracranial hemorrhage on imaging at 24 hours, rate of symptomatic intracranial hemorrhage at 24 hours, and rate of procedure-related adverse events within three months. MAIN RESULTS: Four RCTs were eligible. The current meta-analysis included two trials with 651 participants comparing thrombo-aspiration with stent-retrieval thrombectomy. We judged the quality of evidence to be high in both trials according to Cochrane's risk of bias tool RoB 2. There were no significant differences between thrombo-aspiration and stent-retrieval thrombectomy in rate of mRS of 0 to 2 at three months (risk ratio [RR] 0.97, 95% confidence interval [CI] 0.82 to 1.13; P = 0.68; 633 participants; 2 RCTs); rate of mTICI of 2b to 3 postprocedure (RR 1.01, 95% CI 0.95 to 1.07; P = 0.77; 650 participants; 2 RCTs); all-cause mortality within three months (RR 1.01, 95% CI 0.74 to 1.37; P = 0.95; 633 participants; 2 RCTs); rate of intracranial hemorrhage on imaging at 24 hours (RR 1.03, 95% CI 0.86 to 1.24; P = 0.73; 645 participants; 2 RCTs); rate of symptomatic intracranial hemorrhage at 24 hours (RR 0.90, 95% CI 0.49 to 1.68; P = 0.75; 645 participants; 2 RCTs); and rate of procedure-related adverse events within three months (RR 0.98, 95% CI 0.68 to 1.41; P = 0.90; 651 participants; 2 RCTs). Another two included studies reported no differences for the comparisons of combined therapy versus stent-retrieval thrombectomy or thrombo-aspiration. One RCT is ongoing. AUTHORS' CONCLUSIONS: This review did not establish any difference in safety and effectiveness between the thrombo-aspiration approach and stent-retrieval thrombectomy for treating people with AIS. Furthermore, the combined group did not show any obvious advantage over either intervention applied alone.

Patterns and implications of artery remodeling based on high-resolution vessel wall imaging in symptomatic severe basilar artery stenosis.

Background: Knowledge regarding the influence of arterial remodeling patterns on plaque characteristics and postoperative outcomes in patients with severe basilar artery (BA) stenosis after endovascular treatment is lacking. The purpose of this study was to investigate plaque characteristics, remodeling patterns, and perioperative outcomes in patients with severe BA stenosis. Methods: A prospective cohort study was conducted on symptomatic patients with severe BA stenosis who underwent high-resolution MRI before endovascular treatment. The remodeling index, plaque burden, and area of stenosis were evaluated for each plaque. Based on the remodeling index calculated by high-resolution MRI, remodeling patterns were classified as negative remodeling (NR) or non-negative remodeling (non-NR). Baseline demographics, plaque features, and treatment characteristics were compared between the NR and non-NR groups. Correlations between the remodeling index, plaque burden, and stenosis severity were also examined. Results: In total, 140 eligible patients were included and analyzed, including 91 non-NR cases and 49 NR cases. A strong correlation existed between the remodeling index and plaque burden (r=0.973, P<0.001), and a marginal correlation was observed between the remodeling index and degree of stenosis by area (r=-0.261, P=0.0019). There was no significant difference between the two groups in terms of perioperative complications related to ischemic events and new ischemic cerebral lesions (NICLs). Conclusions: Under the current submaximal angioplasty and/or stenting treatment paradigms, remodeling patterns may not influence the outcome of ischemic events and NICLs. However, the remodeling index is strongly associated with plaque burden, which may provide insight for the evaluation of severe BA stenosis. Further research is warranted.

Endovascular therapy versus medical treatment for symptomatic intracranial artery stenosis.

BACKGROUND: Intracranial artery stenosis (ICAS) is an arterial narrowing in the brain that can cause stroke. Endovascular therapy (ET) and conventional medical treatment (CMT) may prevent recurrent ischaemic stroke caused by ICAS. However, there is no consensus on the best treatment for people with ICAS. OBJECTIVES: To evaluate the safety and efficacy of endovascular therapy plus conventional medical treatment compared with conventional medical treatment alone for the management of symptomatic intracranial artery stenosis. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, four other databases, and three trials registries on 16 August 2022. We contacted study authors and researchers when we required additional information. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing ET plus CMT with CMT alone for the treatment of symptomatic ICAS. ET modalities included angioplasty alone, balloon-mounted stent, and angioplasty followed by placement of a self-expanding stent. CMT included antiplatelet therapy in addition to control of risk factors such as hypertension, hyperlipidaemia, and diabetes. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the records to select eligible RCTs, then extracted data from them. We resolved any disagreements through discussion, reaching consensus decisions among the full team. We assessed risk of bias and applied the GRADE approach to assess the certainty of the evidence. The primary outcome was death by any cause or non-fatal stroke of any type within three months of randomisation. Secondary outcomes included all-cause death or non-fatal stroke of any type occurring more than three months after randomisation, ipsilateral stroke, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, death, restenosis, dependency, and health-related quality of life. MAIN RESULTS: We included four RCTs with 989 participants who had symptomatic ICAS, with an age range of 18 to 85 years. We identified two ongoing RTCs. All trials had high risk of performance bias, as it was impossible to blind participants and personnel to the intervention. Three trials were terminated early. One trial was at high risk of attrition bias because of substantial loss to follow-up after one year and a high proportion of participants transferring from ET to CMT. The certainty of evidence ranged from low to moderate; we downgraded for imprecision. Compared to CMT alone, ET plus CMT probably increases the risk of short-term death or stroke (risk ratio (RR) 2.93, 95% confidence interval (CI) 1.81 to 4.75; 4 RCTs, 989 participants; moderate certainty), short-term ipsilateral stroke (RR 3.26, 95% CI 1.94 to 5.48; 4 RCTs, 989 participants; moderate certainty), short-term ischaemic stroke (RR 2.24, 95% CI 1.30 to 3.87; 4 RCTs, 989 participants; moderate certainty), and long-term death or stroke (RR 1.49, 95% CI 1.12 to 1.99; 4 RCTs, 970 participants; moderate certainty). Compared to CMT alone, ET plus CMT may increase the risk of short-term haemorrhagic stroke (RR 13.49, 95% CI 2.59 to 70.15; 4 RCTs, 989 participants; low certainty), short-term death (RR 5.43, 95% CI 1.21 to 24.40; 4 RCTs, 989 participants; low certainty), and long-term haemorrhagic stroke (RR 7.81, 95% CI 1.43 to 42.59; 3 RCTs, 879 participants; low certainty). It is unclear if ET plus CMT compared with CMT alone has an effect on the risk of short-term transient ischaemic attack (RR 0.79, 95% CI 0.30 to 2.07; 3 RCTs, 344 participants; moderate certainty), long-term transient ischaemic attack (RR 1.05, 95% CI 0.50 to 2.19; 3 RCTs, 335 participants; moderate certainty), long-term ipsilateral stroke (RR 1.78, 95% CI 1.00 to 3.17; 4 RCTs, 970 participants; moderate certainty), long-term ischaemic stroke (RR 1.56, 95% CI 0.77 to 3.16; 4 RCTs, 970 participants; moderate certainty), long-term death (RR 1.61, 95% CI 0.77 to 3.38; 4 RCTs, 951 participants; moderate certainty), and long-term dependency (RR 1.51, 95% CI 0.93 to 2.45; 4 RCTs, 947 participants; moderate certainty). No subgroup analyses significantly modified the effect of ET plus CMT versus CMT alone. The trials included no data on restenosis or health-related quality of life. AUTHORS' CONCLUSIONS: This review provides moderate-certainty evidence that ET plus CMT compared with CMT alone increases the risk of short-term stroke and death in people with recent symptomatic severe ICAS. This effect was still apparent at long-term follow-up but appeared to be due to the early risks of ET; therefore, there may be no clear difference between the interventions in terms of their effects on long-term stroke and death. The impact of delayed ET intervention (more than three weeks after a qualifying event) warrants further study.