Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: a systematic review and meta-analysis of observational data.
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ABSTRACT: Background
Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse.Methods
We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days).Results
The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics.Conclusion
The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty.
SUBMITTER: Kaesmacher J
PROVIDER: S-EPMC8606438 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and purposeData on safety and efficacy of intra-arterial (IA) fibrinolytics as adjunct to mechanical thrombectomy (MT) are sparse.MethodsINtra-arterial FIbriNolytics In ThrombectomY (INFINITY) is a retrospective multi-center observational registry of consecutive patients with anterior circulation large-vessel occlusion ischemic stroke treated with MT and adjunctive administration of IA fibrinolytics (alteplase [tissue plasminogen activator, tPA] or urokinase [UK]) at 10 European centers. Primary outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the European Cooperative Acute Stroke Study II definition. Secondary outcomes were mortality and modified Rankin Scale (mRS) scores at 3 months.ResultsOf 5,612 patients screened, 311 (median age, 74 years; 44.1% female) received additional IA after or during MT (194 MT+IA tPA, 117 MT+IA UK). IA fibrinolytics were mostly administered for rescue of thrombolysis in cerebral infarction (TICI) 0-2b after MT (80.4%, 250/311). sICH occurred in 27 of 308 patients (8.8%), with an increased risk in patients with initial TICI0/1 (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1 to 5.0 per TICI grade decrease) or in those with intracranial internal carotid artery occlusions (aOR, 3.7; 95% CI, 1.2 to 12.5). In patients with attempted rescue of TICI0-2b and available angiographic follow-up, 116 of 228 patients (50.9%) showed any angiographic reperfusion improvement after IA fibrinolytics, which was associated with mRS ≤2 (aOR, 3.1; 95% CI, 1.4 to 6.9).ConclusionsAdministration of IA fibrinolytics as adjunct to MT is performed rarely, but can improve reperfusion, which is associated with better outcomes. Despite a selection bias, an increased risk of sICH seems possible, which underlines the importance of careful patient selection.
| S-EPMC7900401 | biostudies-literature
Project description:Importance:Achieving complete reperfusion is a key determinant of good outcome in patients treated with mechanical thrombectomy (MT). However, data on treatments geared toward improving reperfusion after incomplete MT are sparse. Objective:To determine whether administration of intra-arterial urokinase is safe and improves reperfusion after failed or incomplete MT. Design, Setting, and Participants:This observational cohort study included a consecutive sample of patients treated with second-generation MT from January 1, 2010, through August 4, 2017. Data were collected from the prospective registry of a tertiary care stroke center. Of 1274 patients screened, 69 refused to participate, and 993 met the observational studies inclusion criteria of a large vessel occlusion in the anterior circulation. Data were analyzed from September 1, 2017, through September 20, 2019. Intervention:One hundred patients received intra-arterial urokinase after failed or incomplete MT using manual microcatheter injections. Main Outcomes and Measures:Primary safety outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the Prolyse in Acute Cerebral Thromboembolism II criteria. Secondary end points included 90-day mortality and 90-day functional independence (defined as modified Rankin Scale score of ?2). Efficacy was evaluated angiographically, applying the Thrombolysis in Cerebral Infarction (TICI) scale. Results:After exclusion of patients with posterior circulation strokes and those treated with intra-arterial thrombolytics only, 993 patients were included in the final analyses (median age, 74.6 [interquartile range, 62.6-82.2] years; 505 [50.9%] women). Additional intra-arterial urokinase was administered in 100 patients (10.1%). The most common reason for administering intra-arterial urokinase was incomplete reperfusion (TICI<3) after MT (53 [53.0%]). After adjusting for baseline characteristics underlying case selection, intra-arterial urokinase was not associated with an increased risk of sICH (adjusted odds ratio [aOR], 0.81; 95% CI, 0.31-2.13) or 90-day mortality (aOR, 0.78; 95% CI, 0.43-1.40). Among 53 cases of partial or near-complete reperfusion and treated with intra-arterial urokinase, 32 (60.4%) had early reperfusion improvement, and 18 of 53 (34.0%) had an improvement in TICI grade. Correspondingly, patients treated with intra-arterial urokinase had higher rates of functional independence after adjusting for the selection bias favoring a priori poor TICI grades in the intra-arterial urokinase group (aOR, 1.93; 95% CI, 1.11-3.37). Conclusions and Relevance:In selected patients, adjunctive treatment with intra-arterial urokinase during or after MT was safe and improved angiographic reperfusion. Systemic evaluation of this approach in a multicenter prospective registry or a randomized clinical trial seems warranted.
| S-EPMC6902179 | biostudies-literature
Project description:Background and Purpose: The role of intra-arterial (IA) thrombolysis in modern endovascular therapy is not well-understood. Here, we surveyed neurointerventionalists to understand their current clinical practices and opinions of IA thrombolysis in the new era of mechanical thrombectomy (MT). Method: A 24-question anonymous survey was distributed via email to the members of the Society of Vascular and Interventional Neurology. Results: One hundred and four responses were included in the analysis. Most respondents were interventional neurologists (76.9%) and had ≥5-years in neuro-interventional practice (80.8%). IA thrombolytics are presently used by 60.6%. Aspiration plus stent-retriever was the most common MT approach used with IA-thrombolysis (66.0%). IA-thrombolysis was used in mainly three approaches: (1) treatment of primary distal occlusions, (2) as rescue after proximal occlusion thrombectomy, and (3) or as adjunct therapy to primary MT approach. The most frequent IA-rtPA dose was 3-10 mg, with 1 mg/min infusion rate (56.6%). 84.9% do not have a standardized protocol for administering IA-rtPA. About half (50.9%) believed there should be no time limit for administering IA lytic if there is a favorable imaging profile, while 30.2% indicated ≤6 h. Most respondents (76.5%) would consider using IA-tenecteplase in a trial setting. Only 12.9% felt there was no role for IA thrombolysis in modern endovascular practice. Respondents with ≥10-years' experience were less supportive of the future of IA lytic (98.0 vs. 76.4%, p = 0.006). Conclusion: IA-thrombolysis is currently used in clinical practice; however, there is no clear consensus on best practices or criteria for administration. Further studies are needed to define the role of IA-thrombolysis in the context of MT.
| S-EPMC6863970 | biostudies-literature
Project description:BackgroundThe efficacy and safety of mechanical thrombectomy (MT) in acute large vessel occlusion (LVO) patients with minor stroke (NIHSS ≤ 5) remains undetermined. We aimed to compare the efficacy and safety of intra-arterial thrombolysis (IAT) alone vs. MT for LVO patients with minor stroke.MethodsPatients were selected from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry, a prospective multicenter registry study, and divided into MT and IAT alone groups. We compared the outcome measures between the two groups, including 90-day functional outcome evaluated by the modified Rankin Scale (mRS), the final recanalization level, intracranial hemorrhage, and mortality within 90-days by logistic regression models with adjustment. Besides the conventional multivariable analysis, we performed a sensitivity analysis by adjusting the propensity score to confirm our results. The propensity score was derived using a logistic regression model.ResultsOf the 120 patients, 63 received IAT alone and 57 received MT as the first-line treatment strategy. As compared to MT group, patients in the IAT alone group were associated with a higher chance of 90-day mRS 0-2 [93.7% vs. 71.9%, odds ratio (OR) = 4.75, 95% confidence interval (CI): 1.20-18.80, P = 0.027], a high chance of 90-day mRS 0-3 (96.8% vs. 86.7%, OR = 11.35, 95% CI: 1.93-66.86, P = 0.007), a shorter median time from puncture to recanalization (PTR) (60 min vs. 100 min, β = -63.70, 95% CI: -81.79- -45.61, P < 0.001), a lower chance of any intracranial hemorrhage (ICH) within 48 h (3.2% vs. 19.3%, OR = 0.15, 95% CI: 0.03-0.79, P = 0.025), and a lower chance of mortablity within 90 days (1.6% vs. 9.2%, OR = 0.05, 95% CI: 0.01-0.57, P = 0.016). Similarly, the sensitivity analysis showed the robustness of the primary analysis.ConclusionsCompared with MT, IAT may improve 90-day clinical outcomes with decreased ICH rate and mortality in LVO patients with minor stroke.
| S-EPMC9315389 | biostudies-literature
Project description:Background and purposeRecent advances in intra-arterial techniques and thrombectomy devices lead to high rate of recanalization. However, little is known regarding the effect of the evolvement of endovascular revascularization therapy (ERT) in acute basilar artery occlusion (BAO). We compared the outcome of endovascular mechanical thrombectomy (EMT) versus intra-arterial fibrinolysis (IAF)-based ERT in patients with acute BAO.MethodsAfter retrospectively reviewed a registry of consecutive patients with acute ischemic stroke who underwent ERT from September 2003 to February 2015, 57 patients with acute BAO within 12 hours from stroke onset were enrolled. They were categorized as an IAF group (n=24) and EMT group (n=33) according to the primary technical option. We compared the procedural and clinical outcomes between the groups.ResultsThe time from groin puncture to recanalization was significantly shorter in the EMT group than in the IAF group (48.5 [25.3 to 87.8] vs. 92 [44 to 179] minutes; P=0.02) The rate of complete recanalization was significantly higher in the EMT group than in the IAF group (87.9% vs 41.7%; P<0.01). The good outcome of the modified Rankin Scale score≤2 at 3 months was more frequent in the EMT group than in the IAF group, but it was not statistically significant (39.4% vs 16.7%; P=0.06).ConclusionsEMT-based ERT in patients with acute BAO is superior to IAF-based ERT in terms of the reduction of time from groin puncture to recanalization and the improvement of the rate of complete recanalization.
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Project description:Tirofiban has recently shown encouraging efficacy and safety among acute ischemic stroke (AIS) patients with mechanical thrombectomy (MT). However, the benefits of tirofiban varied among studies depending on the patient's condition, which was often not well analyzed. This study aimed to identify the characteristics of patients who may obtain the largest benefits from tirofiban. The efficacy endpoint was a favorable outcome defined as a modified Rankin Scale (mRS) score of 0~2 at 90 days. The safety endpoints were intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Adjusted logistic regression analysis and subgroup analyses were utilized to investigate the factors associated with tirofiban and the outcome. All of 285 patients fit the inclusion criteria. Tirofiban was associated with a higher rate of favorable outcome (aOR 2.033, 95% CI, 1.002~4.123, p = 0.043) but not with an increased risk of ICH, sICH or mortality (p > 0.05). Moreover, subgroup analyses revealed that tirofiban was associated with favorable outcomes in patients with NIHSS > 14 (aOR 2.778, 95% CI 1.056~7.356, p = 0.038) but not in patients with NIHSS ≤ 14 (aOR 1.719, 95% CI 0.646~4.578, p = 0.278). No significant heterogeneity was found in the effect of tirofiban across the subgroups of age, sex, ASPECTS, time from onset to puncture, use of t-PA or stroke etiology (p for interaction > 0.05). The administration of tirofiban was associated with favorable outcomes in severe ischemic stroke patients, and further studies are needed to confirm this finding.
| S-EPMC9699197 | biostudies-literature
Project description:Background and purposeThe aim of this study was to report the CT evolution and clinical significance of HCA after intra-arterial mechanical thrombectomy (revascularization by using retrievers and/or other mechanical devices without concomitant delivery of intra-arterial thrombolytics) in our patients. These lesions are common after intra-arterial thrombolysis, being considered a negative prognostic sign. Their significance after pure mechanical thrombectomy remains unknown.Materials and methodsForty-eight patients were treated with mechanical thrombectomy by using retrievable stents between April 2010 and February 2011. All patients underwent initial (first 24 hours) and follow-up (48-72 hours) nonenhanced CT. We retrospectively analyzed the clinical and radiologic data of the patients with HCA and compared them with controls.ResultsFifteen of 48 patients presented with HCA. The site of occlusion was the MCA in 7 patients, both the extra- and intracranial segments of the ICA in 6, and the intracranial ICA in 2. In 7 patients, previous intravenous thrombolysis was administered. Complete recanalization (TICI 3) was achieved in 12 patients, and incomplete recanalization (TICI 2b), in 3. The location of HCA was the subarachnoid space in 6 patients, the brain parenchyma in 4 patients, and both in 5 patients. The HCA were asymptomatic in all patients. There was no statistical difference in final NIHSS score reduction (NIHSS pretreatment-NIHSS at discharge) between patients and controls.ConclusionsIn our series, HCA are common after mechanical thrombectomy but do not carry an increased risk of symptomatic hemorrhage or negative prognosis. These data might be related to the high rate of recanalization and the absence of intra-arterial thrombolytics.
| S-EPMC7964764 | biostudies-literature
Project description:IntroductionThe safety and efficacy of tirofiban in intravenous thrombolysis (IVT) bridging to mechanical thrombectomy in patients with acute ischemic stroke (AIS) is unknown. The purpose of this meta-analysis was to evaluate the safety and efficacy of tirofiban in IVT bridging to mechanical thrombectomy in acute ischemic stroke.MethodsWe systematically searched PubMed, EMBASE, Web of Science, and The Cochrane Library, CNKI, and Wan Fang databases for randomized controlled trials and observational studies (case-control studies and cohort studies) comparing the tirofiban and non-tirofiban groups in AIS intravenous thrombolysis bridging to mechanical thrombectomy (Published by November 20, 2021). Our primary safety endpoints were symptomatic cerebral hemorrhage (sICH), intracranial hemorrhage (ICH), postoperative re-occlusion, and 3-month mortality; the efficacy endpoints were 3-month favorable functional outcome (MRS ≤ 2) and successful recanalization rate (modified thrombolytic therapy in cerebral infarction (mTICI) 2b or 3).ResultsA total of 7 studies with 1,176 patients were included in this meta-analysis. A comprehensive analysis of the included literature showed that the difference between the tirofiban and non-tirofiban groups in terms of successful recanalization (OR = 1.19, 95% Cl [0.69, 2.03], p = 0.53, I 2 = 22%) and favorable functional outcome at 3 months (OR = 1.13, 95% Cl [0.81, 1.60], p = 0.47, I 2 = 17%) in patients with IVT bridging mechanical thrombectomy of AIS was not statistically significant. Also, the differences in the incidence of sICH (OR = 0.97, 95% Cl [0.58, 1.62], p = 0.89) and ICH (OR = 0.83, 95% Cl [0.55, 1.24], p = 0.36) between the two groups were not statistically significant. However, the use of tirofiban during IVT bridging mechanical thrombectomy reduced the rate of postoperative re-occlusion (OR = 0.36, 95% Cl [0.14, 0.91], p = 0.03) and mortality within 3 months (OR = 0.54, 95% Cl [0.33, 0.87], p = 0.01) in patients.ConclusionThe use of tirofiban during IVT bridging mechanical thrombectomy for AIS does not increase the risk of sICH and ICH in patients and reduces the risk of postoperative re-occlusion and mortality in patients within 3 months. However, this result needs to be further confirmed by additional large-sample, multicenter, prospective randomized controlled trials.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022297441.
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Project description:BackgroundThe smoking-paradox of a better outcome in ischemic stroke patients who smoke may be due to increased efficacy of thrombolysis. We investigated the effect of smoking on outcome following endovascular therapy (EVT) with mechanical thrombectomy alone versus in combination with intra-arterial (IA-) thrombolysis.MethodsThe primary endpoint was defined by three-month modified Rankin Scale (mRS). We performed a generalized linear model and reported relative risks (RR) for smoking (adjustment for age, sex, hypertension, atrial fibrillation, stroke severity, time to EVT) in patient data stemming from the Virtual International Stroke Trials Archive-Endovascular database.ResultsAmong 1,497 patients, 740(49.4%) were randomized to EVT; among EVT patients, 524(35.0%) received mechanical thrombectomy alone and 216(14.4%) received it in combination with IA-thrombolysis. Smokers (N = 396) had lower mRS scores (mean 2.9 vs. 3.2; p = 0.02) and mortality rates (10% vs. 17.3%; p<0.001) in univariate analysis. In all patients and in patients treated with mechanical thrombectomy alone, smoking had no effect on outcome in regression analyses. In patients who received IA-thrombolysis (N = 216;14%), smoking had an adjusted RR of 1.65 for an mRS≤1 (95%CI 0.77-3.55). Treatment with IA-thrombolysis itself led to reduced RR for favorable outcome (adjusted RR 0.30); interaction analysis of IA-thrombolysis and smoking revealed that non-smokers with IA-thrombolysis had mRS≤2 in 47 cases (30%, adjusted RR 0.53 [0.41-0.69]) while smokers with IA-thrombolysis had mRS≤2 in 23 cases (38%, adjusted RR 0.61 [0.42-0.87]).ConclusionsSmokers had no clear clinical benefit from EVT that incorporates IA-thrombolysis.
| S-EPMC8136663 | biostudies-literature
Project description:BackgroundMost disabling strokes are due to a blockage of a large artery in the brain by a blood clot. Prompt removal of the clot with intra-arterial thrombolytic drugs or mechanical devices, or both, can restore blood flow before major brain damage has occurred, leading to improved recovery. However, these so-called endovascular interventions can cause bleeding in the brain. This is a review of randomised controlled trials of endovascular thrombectomy or intra-arterial thrombolysis, or both, for acute ischaemic stroke.ObjectivesTo assess whether endovascular thrombectomy or intra-arterial interventions, or both, plus medical treatment are superior to medical treatment alone in people with acute ischaemic stroke.Search methodsWe searched the Trials Registers of the Cochrane Stroke Group and Cochrane Vascular Group (last searched 1 September 2020), CENTRAL (the Cochrane Library, 1 September 2020), MEDLINE (May 2010 to 1 September 2020), and Embase (May 2010 to 1 September 2020). We also searched trials registers, screened reference lists, and contacted researchers.Selection criteriaRandomised controlled trials (RCTs) of any endovascular intervention plus medical treatment compared with medical treatment alone in people with definite ischaemic stroke.Data collection and analysisTwo review authors (MBR and MJ) applied the inclusion criteria, extracted data, and assessed trial quality. Two review authors (MBR and HL) assessed risk of bias, and the certainty of the evidence using GRADE. We obtained both published and unpublished data if available. Our primary outcome was favourable functional outcome at the end of the scheduled follow-up period, defined as a modified Rankin Scale score of 0 to 2. Eighteen trials (i.e. all but one included trial) reported their outcome at 90 days. Secondary outcomes were death from all causes at in the acute phase and by the end of follow-up, symptomatic intracranial haemorrhage in the acute phase and by the end of follow-up, neurological status at the end of follow-up, and degree of recanalisation.Main resultsWe included 19 studies with a total of 3793 participants. The majority of participants had large artery occlusion in the anterior circulation, and were treated within six hours of symptom onset with endovascular thrombectomy. Treatment increased the chance of achieving a good functional outcome, defined as a modified Rankin Scale score of 0 to 2: risk ratio (RR) 1.50 (95% confidence interval (CI) 1.37 to 1.63; 3715 participants, 18 RCTs; high-certainty evidence). Treatment also reduced the risk of death at end of follow-up: RR 0.85 (95% CI 0.75 to 0.97; 3793 participants, 19 RCTs; high-certainty evidence) without increasing the risk of symptomatic intracranial haemorrhage in the acute phase: RR 1.46 (95% CI 0.91 to 2.36; 1559 participants, 6 RCTs; high-certainty evidence) or by end of follow-up: RR 1.05 (95% CI 0.72 to 1.52; 1752 participants, 10 RCTs; high-certainty evidence); however, the wide confidence intervals preclude any firm conclusion. Neurological recovery to National Institutes of Health Stroke Scale (NIHSS) score 0 to 1 and degree of recanalisation rates were better in the treatment group: RR 2.03 (95% CI 1.21 to 3.40; 334 participants, 3 RCTs; high-certainty evidence) and RR 3.11 (95% CI 2.18 to 4.42; 268 participants, 3 RCTs; high-certainty evidence), respectively.Authors' conclusionsIn individuals with acute ischaemic stroke due to large artery occlusion in the anterior circulation, endovascular thrombectomy can increase the chance of survival with a good functional outcome without increasing the risk of intracerebral haemorrhage or death.
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