Alteplase For Acute Stroke Research Articles

Comparative safety of tenecteplase vs alteplase for acute ischemic stroke

IntroductionTenecteplase has been compared to alteplase in acute stroke randomized trials, with similar outcomes and safety measures, but higher doses of tenecteplase have been associated with higher hemorrhage rates in some studies. Limited data are available on the safety of tenecteplase outside of clinical trials. MethodsWe examined the safety measures of intracranial hemorrhage, angioedema, and serious extracranial adverse events in a 21-hospital integrated healthcare system that switched from alteplase (0.9 mg/kg, maximum dose 90 mg) to tenecteplase (0.25 mg/kg, maximum dose 25 mg) for acute ischemic stroke. ResultsAmong 3,689 subjects, no significant differences were seen between tenecteplase and alteplase in the rate of intracranial hemorrhage (ICH), parenchymal hemorrhage, or volume of parenchymal hemorrhage. Symptomatic hemorrhage (sICH) was not different between the two agents: sICH by NINDS criteria was 2.0 % for alteplase vs 2.3 % for tenecteplase (P = 0.57), and sICH by SITS criteria was 0.8 % vs 1.1 % (P = 0.39). Adjusted logistic regression models also showed no differences between tenecteplase and alteplase: the odds ratio for tenecteplase (vs alteplase) modeling sICH by NINDS criteria was 0.9 (95 % CI 0.33 - 2.46, P = 0.83) and the odds ratio for tenecteplase modeling sICH by SITS criteria was 1.12 (95 % CI 0.25 - 5.07, P = 0.89). Rates of angioedema and serious extracranial adverse events were low and did not differ between tenecteplase and alteplase. Elapsed door-to-needle times showed a small improvement after the switch to tenecteplase (51.8 % treated in under 30 min with tenecteplase vs 43.5 % with alteplase, P < 0.001). Conclusion: In use outside of clinical trials, complication rates are similar between tenecteplase and alteplase. In the context of a stroke telemedicine program, the rates of hemorrhage observed with either agent were lower than expected based on prior trials and registry data. The more easily prepared tenecteplase was associated with a lower door-to-needle time.

Endovascular thrombectomy with or without intravenous alteplase in acute stroke: a systematic review and meta-analysis of randomized clinical trials.

This study investigated clinical outcomes after direct endovascular thrombectomy (EVT) compared to bridging therapy (EVT with prior intravenous alteplase) in acute stroke within 4.5h after onset. PubMed and Embase were searched for eligible randomized controlled trials. The primary outcome was the rates of neurological functional independence defined as modified Rankin scale score 0-2 at 90days, whose non-inferiority margin was set at - 15%, - 10%, - 6.5%, - 5%, and - 1.3% for its risk difference (RD). We included six studies enrolling 2334 participants. The crude cumulative rates of functional independence were 49.0% with direct EVT vs 50.9% with bridging therapy, without significant difference (Odd ratio [OR] = 0.93, 95% confidence interval [CI] 0.79-1.09) between two groups, where the pooled RD was - 2% (95% CI - 6 to 2%) whose lower 95% CI bound fell within non-inferiority margins of - 15%, - 10%, -6.5%, but not - 5% and - 1.3%. Between the two groups, no significant difference was found in excellent function rate (30.2% vs 30.6%, OR = 0.99, 95% CI 0.82-1.18) with RD of 0% (95% CI - 3 to 4%), mortality rate (16.0% vs 15.0%, OR = 1.08, 95% CI 0.86-1.35) with RD of 1% (95% CI - 2 to 4%), and symptomatic intracranial hemorrhage rate (4.3% vs 5.0%, OR = 0.86, 95% CI 0.58-1.27) with RD of 0% (95% CI - 2 to 1%). No statistical difference was found in functional and safety outcomes between direct EVT and bridging therapy groups in acute stroke within 4.5h after symptom onset. EVT alone was non-inferior to bridging therapy for several, but not the more stringent, non-inferiority margins.

Related factors with orolingual angioedema after intravenous alteplase in acute ischemic stroke: results from a single-center cohort and meta-analysis.

Orolingual angioedema (OA) after intravenous thrombolysis (IVT) with alteplase in acute stroke can be a life-threatening complication. Our aim was to describe its incidence, clinical features, and related factors. We analyzed a single-center cohort of stroke patients treated with IVT in an 8-year period. We compared patients with (OA+) and without OA (OA-). A meta-analysis of previous studies was performed to identify factors related with OA. OA occurred in 7 out of 512 patients (1.37%; 95% CI 0.86-1.88%). Previous hypertension, diabetes, and treatment with ACE inhibitors were more frequent in OA+ compared to OA- patients (100% vs 58%, p = 0.045; 71.4% vs 21.8%, p = 0.008; and 71.4% vs. 16.6%, p = 0.002). Three out of 4 cases with unilateral OA had a contralateral insular infarct. The meta-analysis included 13 studies: 5720 stroke patients treated with IVT and 209 cases of OA. Factors related with OA were ACE inhibitor treatment (RR 5.33 [95% CI 3.07-9.26]) female sex (RR 1.94 [95% CI 1.24-3.03]), hypertension (RR 2.64 [95% CI 1.79-3.90]), diabetes (RR 1.60 [95% CI 1.16-2.21]), and dyslipidemia (RR 1.46 [95% CI 1.00-2.12]). The effect of insular infarct was inconclusive: positive when considering complete infarcts (RR 1.97 [95% CI 1.18-3.29]) and absent when partial infarcts were also included. OA occurred in 1.37% of the IVT-treated stroke patients. Previous treatment with ACE inhibitors, hypertension, diabetes, dyslipidemia, and female sex were associated with OA. The effect of insular infarct needs to be clarified in further studies.

In ischemic stroke, thrombectomy alone was noninferior to thrombectomy plus alteplase for functional outcome at 90 days.

Yang P, Zhang Y, Zhang L, et al. Endovascular thrombectomy with or without intravenous alteplase in acute stroke. N Engl J Med. 2020;382:1981-93. 32374959.

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke

BackgroundIn acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy.MethodsWe conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area.ResultsOf 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P=0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group.ConclusionsIn Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People’s Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.)

Abstract TP401: Impact of Vital Signs and Neurological Assessments After Alteplase for Acute Stroke

Background: Vital signs and neurologic assessments are currently performed using the schedule utilized during the clinical trials which led to the approval of alteplase for acute stroke. These assessments can be disruptive to patients and represent a considerable staffing and infrastructural demand. While the goal of this approach is to improve outcomes by rapidly detecting actionable changes, its impact has been questioned. Despite its widespread use there has been limited systematic review regarding its influence on outcomes. Purpose: This project’s aim was to determine the impact of these assessments by conducting a retrospective review at our large, urban, comprehensive stroke center. We sought to evaluate the rate of compliance with established guidelines, and assess its correlation with patient outcomes. Methods: This retrospective review of patients receiving alteplase for acute stroke was approved by our institutional review board. A total of 130 patients were identified during 2018. Data was collected from the electronic medical record and The Get with the Guidelines database. Results: Our institutional guideline includes a total of 36 vital signs and 24 neurological assessments during first 24-hours after alteplase administration, for a total of 60 assessments. 63% of patients had full compliance with all 60 assessments. The discharge modified Rankin scale (mRS) for those with full compliance was 2.35 versus 2.31 for patients without 100% compliance (p&gt;0.05; NS). There was less compliance with vital signs compared to neurological assessments (73.8% versus 76.9%). Conclusions: The majority of patients were complaint with all assessments however a notable portion missed at least one assessment, occurring more frequently with vital signs. Full compliance with all assessments was not associated with improved mRS.

Acute antithrombotic treatment of ischemic stroke.

Antithrombotic medication is a cornerstone of acute ischemic stroke treatment and secondary prevention. The efficacy of thrombolysis with alteplase in acute stroke has been demonstrated in several clinical trials. This safe and costeffective therapy has transformed the practice of stroke care and has led to subsequent trials of other antithrombotic medications for treatment of ischemic stroke in the acute phase. These antithrombotics include thrombolytic, antiplatelet and anticoagulant agents. While, no other medication has yet demonstrated adequate efficacy, our current and evolving understanding of infarct expansion, ischemic penumbra, collateral circulation and the blood brain barrier is allowing testing of antithrombotic medications tailored to individual patient pathophysiology in clinical trials. This understanding accompanies developments in neuroimaging and organization of stroke care that allow for wide-spread recruitment in these trials. Alteplase remains the mainstay treatment of arterial acute ischemic stroke; however, anticoagulation is the standard therapy for cerebral venous sinus thrombosis. Antithrombotic use in acute stroke, arterial and venous, has demonstrated efficacy but leaves many questions unanswered. This patient population is a fertile ground for novel research, especially as it relates to; combination antithrombotic therapy, combination of pharmacological and mechanical thrombolysis, and the transition to secondary prevention. Here we review the current antithrombotics in the acute phase of ischemic stroke highlighting the evidence-base and areas of uncertainty.

Acute ‘strokenomics’: efficacy and economic analyses of alteplase for acute ischemic stroke

Cerebrovascular disease is the leading cause of adult disability in Western countries and, as such, is associated with a considerable and increasing economic burden. Prevention of disability is preferable to a costly and prolonged period of rehabilitation; however, in this regard, we have only a limited number of acute treatments. Treatment of ischemic stroke with the tissue plasminogen activator alteplase has a considerable and compelling evidence base confirming its clinical efficacy. Good-quality trial data are complemented by years of ‘real-life’ clinical experience. There is limited pharmacoeconomic literature describing the use of alteplase in ischemic stroke, and published data are consistent and broadly supportive of its use in select patient populations. Delivery of stroke and other medical care can differ across countries; however, models based on American, Canadian and European data suggest that following initial monetary investment, net healthcare-associated costs for tissue plasminogen activator-treated patients are less than for untreated contemporaries. Potential savings are driven by reduced disability and associated long-term care costs. At present, robust economic data are only available for the period of 1-year following stroke. Continuing cost savings associated with reduced disability in the longer term make intuitive sense but are yet to be confirmed. A recurring theme in these economic analyses is of reducing healthcare costs associated with the increasing use of thrombolysis. In this regard, it is unfortunate that rates of tissue plasminogen activator utilization remain modest in most centers. This review will discuss the economics of alteplase in acute stroke, making particular reference to the current and projected economic burden of stroke, the evidence base for thrombolysis and published literature on the economics analyses of this therapy.

Life–threatening orolingual angioedema during thrombolysis in acute ischemic stroke

Orolingual angioedema can occur during thrombolysis with alteplase in stroke patients. However, data about its frequency, severity and the significance of concurrent use of angiotensin-converting-enzyme inhibitors (ACEi) are sparse. (1), to alert to the potentially life-threatening complication of orolingual angioedema. (2), to present CT-scans of the tongue which exclude lingual hematoma. (3), to estimate the frequency of orolingual angioedema. (4), to evaluate the risk associated with the concurrent use of ACEi. Single center, databank-based observational study on 120 consecutive patients with i. v. alteplase for acute stroke. Meta-analysis of all stroke studies on alteplase-associated angioedema, which provided detailed information about the use of ACE-inhibitors. Across studies, the Peto odds ratio of orolingual angioedema for "concurrent use of ACEi" was calculated. Orolingual angioedema occurred in 2 of 120 patients (1.7%, 95% CI 0.2-5.9 %). Angioedema was mild in one, but rapidly progressive in another patient. Impending asphyxia prompted immediate intubation. CT showed orolingual swelling but no bleeding. One of 19 (5%) patients taking ACEi had orolingual angioedema, compared to 1 of 101 (1%) patients without ACEi. Medline search identified one further study about the occurrence of alteplase-associated angioedema in stroke patients stratified to the use of ACEi. Peto odds ratio of 37 (95 % CI 8-171) indicated an increased risk of alteplasetriggered angioedema for patients with ACEi (p <0.001). Orolingual angioedema is a potentially life-threatening complication of alteplase treatment in stroke patients, especially in those with ACEi. Orolingual hematoma as differential diagnosis can be excluded by CT-scan.