Studies Of Factors Analysis And Intervention Strategies Of Futile Recanalization Following Endovascular Therapy For Acute Ischemic Stroke

Acute ischemic stroke is a common cerebrovascular disease with high morbidity,mortality,disability and recurrence rates,and is a serious risk to human health and quality of life.Endovascular treatment has become a first-line treatment for acute intracranial large vessel occlusion,which can significantly improve the neurological function prognosis of patients.However,more and more studies have found that the high recanalization rate of occluded vessels has not been fully translated into clinical benefits for patients with acute ischemic stroke,and more than half of the patients still have poor neurological function prognosis,which is clinically known as "unsuccessful recanalization".Therefore,the treatment strategy solely aimed at improving the recanalization rate of occluded vessels cannot fundamentally improve the clinical prognosis of patients with acute ischemic stroke.There are still other factors affecting the relationship between vessel recanalization and good functional prognosis.At present,the pathological and physiological mechanisms and influencing factors of ineffective recanalization in endovascular treatment have not been fully elucidated,especially the mechanisms and influencing factors of ineffective recanalization in acute intracranial large vessel occlusion after acute stroke are still little known.Many issues regarding ineffective recanalization in endovascular treatment of acute ischemic stroke are still unresolved.Therefore,analyzing the potential causes and pathological and physiological mechanisms of ineffective recanalization in endovascular treatment and conducting intervention treatment may improve the clinical prognosis of patients with acute intracranial large vessel occlusion and provide new ideas for the treatment of acute cerebrovascular diseases.Based on two national multi-center clinical research databases,this study explores the influencing factors of ineffective recanalization in endovascular treatment and the effect of perioperative intravenous injection of tirofiban on the clinical prognosis of patients with acute ischemic stroke,providing reference for optimizing the treatment strategy for patients with acute ischemic stroke and reducing ineffective recanalization in endovascular treatment.Part 1 Association with Stroke Severity and Futile Recanalization with Endovascular Therapy in Patients with Acute Posterior Circulation Ischemic StrokeBackground and purpose: Endovascular therapy(EVT)has been reported to be safe and effective with improving the clinical outcomes in acute basilar artery occlusion(ABAO)patients.However,the clinical benefits of EVT remain uncertain in ABAO patients with severe symptoms(National Institutes of Health Stroke Scale [NIHSS] score ≥21).The aim of this study was to investigate the correlation between stroke severity and clinical outcomes of EVT in patients with acute basilar artery occlusion and to further identify factors associated with futile recanalization among patients with ABAO and severe symptoms.Methods: The Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry(BASILAR)is a prospective,nationwide registry study that enrolled consecutive patients with acute basilar artery occlusion within 24 hours of onset from January 2014 to May 2019 in China from.Included patients had ABAO and underwent EVT or standard medical treatment(SMT)alone in routine clinical practice.Patients were dichotomized into severe symptoms(NIHSS score ≥21)and minor to moderate symptoms(NIHSS score<21)groups.Patients were followed up for 90 days.EVT with SMT vs SMT alone.The primary outcome was improvement in modified Rankin Scale(m RS)score at 90 days,defined as a decrease by 1 grade in m RS score.Secondary outcomes included favorable functional outcome(m RS score,0-3)and mortality.Results: A total of 542 patients with ABAO and severe symptoms(median [IQR] age,65[57-74] years;147 [27.1%] women),and there were 431 patients in the EVT group with a baseline NIHSS score of 30(27-35)and 111 patients in the SMT group with a baseline NIHSS score of 32(28-35).Compared with SMT,EVT was associated with increased odds of improved m RS score(adjusted common odds ratio [OR],3.44 [95% CI,2.05-5.78];P<0.001),with increased odds of a favorable functional outcome(m RS score,0-3;adjusted OR,4.52 [95% CI,1.64-12.43];P =0.004)and decreased odds of mortality(adjusted OR,0.27 [95% CI,0.15-0.50];P<0.001).Among patients receiving EVT,baseline NIHSS score was associated with decreased odds of a favorable functional outcome(adjusted OR per1-point increase in score,0.90 [95% CI,0.85-0.95];P <0.001)and increased odds of mortality(adjusted OR per 1-point increase in score,1.13 [95% CI,1.07-1.19];P <0.001),while posterior circulation Acute Stroke Prognosis Early Computed Tomography Score(pc-ASPECTS)was associated with increased odds of a favorable functional outcome(adjusted OR per 1-point increase in score,1.71 [95% CI,1.41-2.07];P <0.001)and decreased odds of mortality(adjusted OR per 1-point increase in score,0.74 [95% CI,0.64-0.85];P<0.001).Different occlusion sites,compared with distal basilar artery,were associated with decreased odds of favorable functional outcome(middle basilar artery:adjusted OR versus distal basilar artery,0.36 [95% CI,0.17-0.80];P=0.01).Conclusions: This study found that EVT was associated with increased odds of functional favorable outcomes among patients with ABAO and severe symptoms.The incidence of futile recanalization following EVT increased with increasing baseline NIHSS score.EVT should be considered with caution in patients when baseline NIHSS score was greater than or equal to 35.Baseline NIHSS score,pc-ASPECTS,and occlusion site were independent factors on futile recanalization with EVT.These findings remain to be further confirmed by randomised controlled trials.Part 2 Association with Tirofiban Treatment and Futile Recanalization with Endovascular Therapy in Patients with Acute Anterior Circulation Ischemic Stroke Based on Imaging ScreeningBackground and purpose: Tirofiban,a highly selective platelet glycoprotein IIb/IIIa inhibitor that reduces early arterial re-occlusion and improves neurological outcome,has been widely used in the EVT of acute ischaemic stroke in large arteries with atherosclerosis.However,the RESCUE BT trial found that the combination of tirofiban early in the EVT did not significantly improve neurological function in patients.In this study,the RESCUE BT study population was screened according to the DAWN and DEFUSE 3 study criteria,in accordance with current American Heart Association(AHA)guidelines,to determine the efficacy and safety of early EVT with tirofiban in patients with acute anterior circulation large vessel occlusive stroke,to explore the benefit of intravenous tirofiban in patients with acute anterior circulation large vessel occlusive stroke,and to optimize the number of patients treated with endovascular therapy.screening and reducing futile recanalization following EVT.Methods: This is a post-hoc analysis of a multicenter,double-blinded,randomized,placebo-controlled trial that was conducted at 55 centers in China and involved 950 participants with stroke with large vessel anterior circulation occlusion from October 2018 to October 2021.The patients who were eligible for endovascular thrombectomy in 6-hour window and met the DAWN or DEFUSE 3 trials eligibility criteria in extended window according to current AHA/ASA guideline was analyzed.The primary outcome was the distribution of the 90-day modified Rankin scale(m RS)scores.Secondary outcomes included the rates of functionally independent(m RS score 0-2)and favorable outcome(m RS score 0-3).Safety outcomes included the incidences of symptomatic intracranial hemorrhage(s ICH)within 48 hours and 90-day mortality.Results: A total of 652 patients who met current AHA/ASA guidelines were included in this study for analysis,including 319 in the tirofiban group and 333 in the placebo group,both with a median age(M)of 68 years,an interquartile range(IQR)of 58-74 years and 58-75 years,respectively,and 136 and 142 female patients,both 42.6%.The median 90-day m RS score was 3(IQR,1-4)in tirofiban group,and 3(IQR,1-4)in placebo group.The adjusted common odds ratio(OR)for a lower level of disability with tirofiban than placebo was 1.08(95% confidence interval [CI],0.83-1.42;P=0.57).Incidence of s ICH(10.1% versus 6.3%;adjusted OR 1.70;[95% CI,0.95-3.04];P=0.08)was not significantly different between groups.However,intravenous tirofiban might be associated with lower disability level(adjusted common OR,1.74 [95% CI,1.14-2.65];P=0.01)in large artery atherosclerosis patients;and in patients with cardiogenic embolism,intravenous tirofiban may be associated with increased s ICH(10.8% versus 4.6%;corrected OR,3.27;95% CI.1.24-8.61,P=0.02)and even increased mortality(20.9% versus 11.9%;corrected OR,2.32;95% CI: 1.20-4.51,P=0.01).Conclusions: There was no significant difference in severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent EVT according to current AHA/ASA guidelines.By optimizing patient screening,this study found that intravenous tirofiban improved the clinical functional prognosis of endovascular treatment in patients with large artery atherosclerotic stroke,while being associated with increased s ICH and mortality in patients with cardiogenic embolism.These findings still need to be further confirmed in randomised controlled trials.Part 3 Effect of Perioperative Intravenous Tirofiban Treatment on The Preferred Thrombectomy Strategy and Futile Recanalization with Endovascular Therapy in Patients with Acute Anterior Circulation Ischemic StrokeBackground and purpose: Aspiration is the first-line technique together with stent retriever in patients with acute large-vessel occlusive stroke in the anterior circulation,the clinical outcome of the aspiration technique is not inferior to that of the first-line stent retriever technique.However,it is unclear whether intravenous tirofiban administered prior to endovascular therapy(EVT)affects the clinical outcome of the first-line technique during EVT.This study aimed to investigate whether the effect of intravenous tirofiban treatment before EVT on outcome is modified by first-line technique during EVT,to optimize the first-line technique for endovascular treatment and to reduce ineffective recanalization of EVT.Methods: This was a post hoc analysis from RESCUE BT(Endovascular Treatment With versus Without Tirofiban for Stroke Patients with Large Vessel Occlusion),multicenter,double-blinded,randomized,placebo-controlled trial,enrolling 950 consecutive patients with anterior circulation large vessel occlusive stroke within 24 hours of onset at 55 stroke centers in China from October 2018 to October 2021.We included data from all patients who underwent EVT with stent retriever or aspiration thrombectomy attempt.We compared patients treated with stent retriever(with or without aspiration)to aspiration alone as first-line EVT technique and assessed the interaction of first-line EVT technique with tirofiban treatment.The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale score at 90 days,analyzed with ordinal regression for a shift towards better outcome.Secondary outcomes included functional independence(90-day modified Rankin Scale score 0-2)and successful reperfusion(modified Thrombolysis in Cerebral Infarction score 2b-3).Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality.Results: A total of 830 patients were included in this study,464 patients(55.9%)were treated with a stent retriever as first-line device and 366 treated with an aspiration alone as first-line device.In the full population,functional outcome was similar for patients treated with stent retriever versus aspiration only(adjusted common odds ratio [ac OR]? 0.79;95% CI: 0.62–1.02;P=0.07).We observed a non-significant interaction between tirofiban and first-line EVT technique(P=0.58).Functional outcome did not differ between patients treated with or without tirofiban in the stent retriever group(adjusted common OR,0.98;95% CI: 0.87–1.10;P=0.72)and in the aspiration-only group(adjusted common OR,1.02;95% CI: 0.88–1.18;P=0.80).In stent retrievergroup,perioperative intravenous tirofiban reduced savage therapy(20.8% vs.31.0%,adjusted OR,0.51;95% CI: 0.32~0.83;P=0.007)and increased the first pass effect of endovascular therapy(36.8% vs.28.2%,adjusted OR,1.54;95% CI: 1.004~ 2.37;P=0.048).In the aspiration-only group,patients treated with tirofiban had higher s ICH compared to those treated with placebo(adjusted OR,2.31;95% CI: 1.03–5.20;P=0.04).Perioperative intravenous tirofiban did not increase the rate of successful revascularization in patients with preferred stent retriever group(93.9% versus 90.9%,adjusted OR,1.47;95% CI: 0.66~3.25,P=0.34)and preferred aspiration group(94.8% versus 94.3%,adjusted OR,0.84,95% CI: 0.32~ 2.22,P=0.72).There was no statistically significant interaction for successful reperfusion.Conclusions: In RESCUE BT trial,the treatment effect of tirofiban wasn’t modified by first-line EVT technique.Patients treated with aspiration only as first-line technique had higher s ICH if they did receive tirofiban treatment in patients with acute anterior circulation large vessel occlusive stroke.No such difference was observed in patients treated with stent retrievers.Confirmation by pooling with results from other trials is needed to confirm these findings.