Alteplase For Acute Ischemic Stroke Research Articles

Alteplase for Acute Ischemic Stroke in Patients Aged >80 Years: Pooled Analyses of Individual Patient Data.

Expert guidelines specify no upper age limit for alteplase for thrombolysis of acute ischemic stroke (AIS) but, until recently, European regulatory criteria restricted its use to patients aged 18 to 80 years. We performed pooled analyses of randomized controlled trial (RCT) and registry data to evaluate the benefit-risk profile of alteplase for AIS among patients aged >80 years to support a regulatory application to lift the upper age restriction. Individual patient data were evaluated from 7 randomized trials of alteplase (0.9 mg/kg) versus placebo or open control for AIS, and the European SITS-UTMOST registry database. Clinical outcomes, including good functional outcome (score 0-1, modified Rankin Scale day 90 or Oxford Handicap Score day 180), were evaluated in the full RCT and registry populations, and specified age-based subgroups (≤80 or >80 years) who met existing European regulatory criteria for alteplase, excluding upper age restriction. Regardless of treatment allocation, 90-day mortality was lower among RCT patients aged ≤80 versus >80 years who otherwise met existing European regulatory criteria (246/2405 [10.2%] versus 307/1028 [29.9%], respectively). Among patients aged >80 years, alteplase versus placebo was associated with a higher proportion of good stroke outcome (modified Rankin Scale score 0-1; 99/518 [19.1%] versus 67/510 [13.1%]; P=0.0109) and similar 90-day mortality (153/518 [29.5%] versus 154/510 [30.2%]; P=0.8382). The odds of a good stroke outcome following alteplase allocation in the full RCT population were independent of age (P=0.7383). Good stroke outcome was reported for almost half (4821/11 169 [43.2%]) of the patients who received alteplase in routine practice. Outcomes in routine practice supported those achieved in RCTs. Alteplase for AIS has a positive benefit-risk profile among patients aged >80 years when administered according to other regulatory criteria. Alteplase for AIS should be evaluated on an individual benefit-risk basis.

Predictors of Postthrombolysis Outcome and Symptomatic Postthrombolysis Hemorrhage following Intravenous Thrombolysis with Alteplase for Acute Ischemic Stroke.

Background Thrombolysis improves the outcome in acute ischemic stroke (AIS), albeit with an increased risk of symptomatic intracranial hemorrhage (sICH). Biomarkers to find patients at risk of sICH, and guide treatment and prognosis would be valuable. Methods Consecutive patients of AIS thrombolysed between February 2017 and September 2019 at Calcutta National Medical College were studied prospectively for sICH and outcome at 6-month follow-up. We identified the independent risk factors for unfavorable outcomes, mortality, and sICH using multivariate analysis. Prethrombolysis and 24-hour postthrombolysis fibrinogen levels were estimated to evaluate its biomarker role. Results Out of 180 AIS patients admitted during the study period, 60 patients were thrombolysed. Door to needle time was <3 hours among 24 patients and 3 to 4.5 hours among 36 patients. Favorable outcomes occurred among 76.67% and sICH occurred among 13.33% patients. Upper tertile of National Institute of Health Stroke Scale (NIHSS) had the highest adjusted odds for sICH (17.5 [95% confidence intervals=1.7–178.44]). Total anterior circulation stroke had the highest adjusted odds for unfavorable outcome (19.11 [3.9–92.6]). Following thrombolysis, the mean (standard deviation) fibrinogen level of 449.27 (32.87) decreased 7% to postthrombolysis level of 420 (20.5; p< 0.0001). Higher tertiles of fibrinogen levels had progressively increasing odds for morbidity and sICH. Conclusion Congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke (double weight), i.e., CHADS2 score >2, low ejection fraction, the occurrence of total anterior circulation stroke and higher mean arterial blood pressure, blood glucose level, NIHSS score, and fibrinogen at admission were the common risk factors significantly predicting postthrombolysis sICH and morbidity. Antiplatelet and anticoagulant therapy, lower ASPECT (Alberta Stroke Program Early CT Score), and higher SEDAN scores also predicted sICH . Fibrinogen levels were significantly higher among those developing sICH and having unfavorable outcome. The performance of thrombolysis within 3 hours or between 3 and 4.5 hours after symptom onset did not affect morbidity, mortality, or the occurrence of sICH.

Using Tenecteplase for Acute Ischemic Stroke: What Is the Hold Up?

Alteplase is the only Food and Drug Administration-approved intravenous (IV) thrombolytic medication for acute ischemic stroke. However, multiple recent studies comparing tenecteplase and alteplase suggest that tenecteplase is at least as efficacious as alteplase with regards to neurologic improvement. When given at 0.25 milligrams per kilogram (mg/kg), tenecteplase may have less bleeding complications than alteplase as well. This narrative review evaluates the literature and addresses the practical issues with regards to the use of tenecteplase versus alteplase for acute ischemic stroke, and it recommends that physicians consider tenecteplase rather than alteplase for thrombolysis of acute ischemic stroke.

Abstract WP429: A Nurse Driven Acute Stroke Alert Process Improves Treatment Times and Treatment Rates

Introduction: Treatment time has gained sufficient popularity because it is now well-known that “Time is Brain”. Treatment rates, however, lag behind in importance even though more lives can be saved by treating more often. Our TJC Comprehensive Stroke Center has a nurse-led stroke alert process that focuses on multiple, rapid, parallel steps to reduce DTN for IV alteplase. The Baptist Emergency Stroke Team (BEST) responders are highly-trained and skilled nurses that assess, coordinate, and initiate processes to ensure the best times. We identified that our treatment rate was lower than the national rate for certified CSCs, so the BEST responders used a stepwise process to develop their own interventions to improve rates. Methods: First, the BEST responders started tracking our monthly rate. Next, they set a rate goal, and then brainstormed how to influence treatment decision-making. The BEST team initiated a monthly PI meeting that focused on the importance of treating disability rather than an NIHSS score. Then the team scripted and rehearsed critical conversations to have providers that advocated specifically for treating disability. The team adopted the motto, “Treat Disability, Not Numbers”. Results Conclusions: Our CSC observed a small decrease in median DTN but double the treatment rate after the BEST responder intervention. In comparison, these statistics did not change at the national CSC level. The sICH rate was reduced from Period A to C, meaning that increased treatment rate did not lead to increased hemorrhagic rate. Nursing initiatives can have a substantial positive effect on increasing the number of patients treated with IV alteplase for acute ischemic stroke.

Abstract TMP14: Contemporary Use of IV Alteplase in Acute Ischemic Stroke Beyond 4.5 Hours of Stroke Onset in Clinical Practice is Rare

Introduction: Two RCTs conducted from 2010-2018 showed benefit in ischemic stroke (IS) of IV tPA &gt;4.5 h from last known well (LKW) using advanced imaging selection. Many subjects were wakeup strokes treated &lt; 4.5 h of symptom discovery (SxD). We assessed the frequency of IV tPA &gt; 4.5 h in the national GWTG-Stroke clinical registry during the same period as the RCTs were performed. Methods: We analyzed all IS hospitalizations between 1/1/09 - 10/1/18 at fully participating GWTG-Stroke sites to identify 219,565 patients at 1919 sites who received IV tPA (no thrombectomy) and had valid LKW, SxD and treatment times recorded. Table shows significant covariates (standardized differences &gt;10%) Results: Treatment beyond 4.5 h from LKW was rare, occurring in 2.19% (n=4798) of all tPA cases, and 50% of those treated were still within 4.5 h from SxD. The distribution of time to treatment in minutes was similar when stroke onset was defined by LKW compared to SxD (median (IQR) 134 (100-174) vs. 125 (94-163)) (Fig). The use of IV tPA at &gt;4.5 h from LKW as a proportion of all tPA cases treated varied substantially across sites (median (IQR) 1.7% (0-3.1%)) but fewer than ~10% of sites had more than 5% of their tPA use occurring beyond 4.5 h. Compared to &lt; 4.5 h, patients treated &gt;4.5 h differed in age, AF, arrival mode/time, stroke severity and hospital region (Table). Conclusions: During the past decade and prior to published RCT evidence that extended window IV tPA was effective, US sites in GWTG-Stroke rarely treated patients beyond the guideline-approved window of 4.5 h. It will be important to monitor adoption of extended window thrombolysis in the US, and determine if additional RCT data are required to change practice.

Abstract WP281: Pharmacists Improve Door to Needle Times in the Emergency Department

Background: An estimated two million brain cells die every minute cerebral perfusion is impaired. The best outcomes for acute ischemic strokes are achieved by decreasing the time from emergency department (ED) arrival to thrombolytic therapy. Alteplase, a high risk medication, was dosed and prepared in the pharmacy. This contributed to prolonged door to needle (DTN) times. Purpose: To describe the impact of pharmacist interventions on DTN times in the ED. Methods: All patients who received alteplase for acute ischemic stroke from January 2012 to April 2019 were reviewed. In November 2012, the ED pharmacy program began with a dedicated ED pharmacist for 8 hours a day and expanded to 13 hours a day in September 2014. During those hours alteplase was prepared at bedside in the ED. In November 2015, all pharmacists were trained on the ED code stroke process. Monthly case reviews and DTN times were reported to the stroke coordinators starting January 2017. Alteplase preparation and administration in the computed tomography (CT) room started April 2017. Following comprehensive stroke center certification, routine stroke competency exams were administered to pharmacists in 2018. In 2019, pharmacists started reporting DTN times at neuroscience core team meetings. Results: During this time frame, a total of 407 patients received alteplase. Average DTN times decreased from a baseline of 130.9 minutes to 45.3 minutes. Interventions that resulted in the largest decrease in average DTN times were the expanded ED service hours (34.6 minutes) and pharmacist preparation of alteplase in the CT room (21.9 minutes). Conclusions: Pharmacists directly impacted stroke care in the ED by decreasing DTN times. Presence of a pharmacist in the ED enabled fast and safe delivery of alteplase by ensuring accurate dosing and preparation. Pharmacists also performed rapid medication reconciliation and expedited antihypertensive therapies. In conclusion, having pharmacists as part of the stroke team is a model that could be adopted by hospitals to enhance stroke care.

Abstract WP411: Asymptomatic Hemorrhage Predicts Delayed Symptomatic Hemorrhage After Alteplase in Acute Ischemic Stroke

Background: Predictors of alteplase associated symptomatic intracranial hemorrhage (sICH) have been identified but there are very limited data on predictors of delayed sICH (&gt; 24 hours from infusion). We hypothesize that asymptomatic hemorrhage on 24 hour brain imaging predicts delayed sICH and that delaying antithrombotic treatment in these patients reduces this risk. Methods: This is a retrospective analysis of a prospective quality improvement database of a comprehensive stroke center. We included all patients with a discharge diagnosis of ischemic stroke who received alteplase. Patients with sICH occurring within 24 hours from alteplase and those whose code status was changed to comfort measures only were excluded. Delayed sICH was defined as any hemorrhage causing neurological deterioration. We compared baseline characteristics, asymptomatic hemorrhage on 24 hour brain imaging, and median time to initiating antithrombotic therapy between patients with and without delayed sICH. Results: Among 606 patients who met our inclusion criteria; mean age was 70 years and 52% were men; 23.8% had asymptomatic hemorrhage on 24 hour brain imaging (CT or MRI) and 12 patients (2%) had delayed sICH. Aspirin was the most common initial antithrombotic (91.2%) followed by plavix (2.6%), and others (3.8%). After adjusting for confounders, asymptomatic hemorrhage on 24 hour brain imaging was associated with increased odds of delayed sICH (OR 5.5, 95% CI 1.52 - 19.87, p = 0.009) but the median time (days) to starting antithrombotic therapy did not differ between those with asymptomatic hemorrhage who developed delayed sICH vs. those who did not [2 (3) vs. 3 (5), p = 0.447). Conclusion: Delayed sICH in patients receiving alteplase is uncommon and asymptomatic hemorrhage is a strong predictor. Delaying initiation of antithrombotic treatment in patients with asymptomatic hemorrhage on 24 hour imaging was not associated with reduced delayed sICH risk. It is possible that other factors such as reperfusion and blood brain barrier disruption are more important determinants of delayed sICH risk as opposed to timing of antithrombotic therapy initiation.

Our experience with stroke thrombolysis at a tertiary care center in South India

Introduction: Intravenous (IV) thrombolysis is the cornerstone of the treatment of acute ischemic stroke in modern stroke era. Alteplase, also known as recombinant tissue plasminogen activator, is currently the only approved drug for IV thrombolysis worldwide and is used for the treatment of acute ischemic stroke. Objective: The objective was to study the clinical efficacy and safety of IV thrombolysis with alteplase in acute ischemic stroke. Materials and Methods: We consecutively enrolled acute ischemic stroke patients who underwent IV thrombolysis with alteplase from October 2017 to May 2018. Primary clinical efficacy outcome was defined as an improvement in the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at 24 h. The secondary clinical efficacy outcome was the favorable outcome on the modified Rankin scale at 90 days, which is defined as a score of 0 or 1. The safety endpoints were death rate at 90 days and symptomatic intracranial hemorrhage (SICH). Results: The mean NIHSS scores at baseline and 24 h were 13.56 (±4.56) and 9.92 (±6.13), respectively, the difference being statistically significant (P Conclusion: This study confirms the efficacy and safety of alteplase for stroke thrombolysis in our clinical setting.

Intravenous thrombolysis with 0.9 mg/kg alteplase for acute ischaemic stroke: a network meta-analysis of treatment delay

ObjectivesThe aim of this study was to evaluate the effect of alteplase in intravenous thrombolysis of acute ischaemic stroke (AIS) regarding the different time windows of treatment (<3 hours, 3–4.5...

Effect of Alteplase Administration on International Normalized Ratio in Patients With Acute Ischemic Stroke.

Alteplase may elevate international normalized ratio (INR) results, although the exact rate of elevation occurrence is not firmly established in the literature. The purpose of this study is to determine the occurrence rate of INR elevation following alteplase administration. We also aimed to determine what factors are independently associated with the development of elevated INR following alteplase administration for ischemic stroke. We conducted a multicenter, retrospective, cohort study of patients who received alteplase for acute ischemic stroke. Patients were screened for baseline INR measurement and a repeat value within 24 hours of alteplase administration. The primary outcome was the percent of patients who experienced ≥0.4-point increase in INR. Secondary outcomes included the rate of adverse bleeding events and identification of factors independently associated with elevated INR following alteplase administration. Two hundred and sixty-one patients were included, with 44 (16.9%) patients having an INR increase of 0.4 or more. Patients with an INR increase ≥0.4 experienced a nonstatistically significant increase in bleeding episodes (8.8% vs 18.2%; P = .10). We identified African American race (odds ratio, 3.48, 95% confidence interval, 1.5-7.6; P = .002) as an independent predictor of INR increase ≥0.04. An INR elevation is common following receipt of alteplase for ischemic stroke. Those of African American race were at increased risk of INR elevation; however, more studies are needed to determine whether these patients are at a higher bleeding risk as a result of INR elevation.

Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke: Meta-Analysis of 5 Randomized Trials.

Background and Purpose- TNK (tenecteplase), a newer fibrinolytic agent, has practical delivery advantages over ALT (alteplase) that would make it a useful agent if noninferior in acute ischemic stroke treatment outcome. Accordingly, the most recent US American Heart Association/American Stroke Association acute ischemic stroke guideline recognized TNK as an alternative to ALT, but only based on informal consideration, rather than formal meta-analysis, of completed randomized control trials. Methods- Systematic literature search and formal meta-analysis were conducted per PRISMA guidelines (Preferred Reporting Items for Systemic Reviews and Meta-Analyses), adapted to noninferiority analysis. The primary outcome of freedom from disability (modified Rankin Scale score, 0-1) outcome at 3 m, and additional efficacy and safety outcomes, were analyzed. Results- Systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% male, baseline National Institutes of Health Stroke Scale mean 7.0, and time from last known well to treatment start mean 148 minutes. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary end point, crude cumulative rates of disability-free (modified Rankin Scale score, 0-1) 3 m outcome were TNK 57.9% versus ALT 55.4%. Informal, random-effects meta-analysis, the risk difference was 4% (95% CI, -1% to 8%). The lower 95% CI bound fell well within the prespecified noninferiority margin. Similar results were seen for the additional efficacy end points: functional independence (modified Rankin Scale score, 0-2): crude TNK 71.9% versus ALT 70.5%, risk difference 2% (95% CI, -3% to 6%); and modified Rankin Scale shift analysis, common odds ratio 1.21 (95% CI, 0.93-1.57). For safety end points, lower event rates reduced power, but point estimates were also consistent with noninferiority Conclusions- Accumulated clinical trial data provides strong evidence that TNK is noninferior to ALT in the treatment of acute ischemic stroke. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.

Who will benefit more from low-dose alteplase in acute ischemic stroke?

Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine individual patient factors that contribute to the risk-benefit balance of low-dose alteplase treatment. Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic stroke patients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for individual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by dividing excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148 vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). Use of low-dose alteplase may be preferable in acute ischemic stroke patients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms.

Outcome of Thrombolysis with Alteplase in Acute Ischemic Stroke

Outcome of Thrombolysis with Alteplase in Acute Ischemic Stroke

Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial

Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke. We did an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more, who were screened at 110 sites in 15 countries. Eligible patients were randomly assigned (1:1, by means of a central, web-based program) within 6 h of stroke onset to receive intensive (target systolic blood pressure 130-140 mm Hg within 1 h) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 h. The primary outcome was functional status at 90 days measured by shift in modified Rankin scale scores, analysed with unadjusted ordinal logistic regression. The key safety outcome was any intracranial haemorrhage. Primary and safety outcome assessments were done in a blinded manner. Analyses were done on intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01422616. Between March 3, 2012, and April 30, 2018, 2227 patients were randomly allocated to treatment groups. After exclusion of 31 patients because of missing consent or mistaken or duplicate randomisation, 2196 alteplase-eligible patients with acute ischaemic stroke were included: 1081 in the intensive group and 1115 in the guideline group, with 1466 (67·4%) administered a standard dose among the 2175 actually given intravenous alteplase. Median time from stroke onset to randomisation was 3·3 h (IQR 2·6-4·1). Mean systolic blood pressure over 24 h was 144·3 mm Hg (SD 10·2) in the intensive group and 149·8 mm Hg (12·0) in the guideline group (p<0·0001). Primary outcome data were available for 1072 patients in the intensive group and 1108 in the guideline group. Functional status (mRS score distribution) at 90 days did not differ between groups (unadjusted odds ratio [OR] 1·01, 95% CI 0·87-1·17, p=0·8702). Fewer patients in the intensive group (160 [14·8%] of 1081) than in the guideline group (209 [18·7%] of 1115) had any intracranial haemorrhage (OR 0·75, 0·60-0·94, p=0·0137). The number of patients with any serious adverse event did not differ significantly between the intensive group (210 [19·4%] of 1081) and the guideline group (245 [22·0%] of 1115; OR 0·86, 0·70-1·05, p=0·1412). There was no evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome. Although intensive blood pressure lowering is safe, the observed reduction in intracranial haemorrhage did not lead to improved clinical outcome compared with guideline treatment. These results might not support a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischaemic stroke. Further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering in this patient group. National Health and Medical Research Council of Australia; UK Stroke Association; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.

Abstract 81: Tenecteplase is Non-Inferior to Alteplase for Acute Ischemic Stroke: Formal Meta-Analysis of 5 Completed Randomized Trials

Background: Tenecteplase (TNK), a newer lytic easier to administer than alteplase (ALT), was recognized in the 2018 US AHA/ASA Guideline Update as an alternative to ALT in patients with acute ischemic stroke (AIS). But this recommendation was advanced based on informal consideration, rather than formal meta-analysis, of completed RCTs. Methods: Systematic literature search identified all RCTs comparing TNK vs ALT; formal non-inferiority meta-analysis was conducted per PRISMA guidelines. Based on a prior non-inferiority lytic AIS trial (ENCHANTED), the primary meta-analytic endpoint was disability-free (mRS 0-1) outcome at 3m, with a non-inferiority margin of 0.88. Additional efficacy and safety outcomes were also analyzed. Results: The systematic search identified 5 trials enrolling 1585 patients (828 TNK, 757 ALT). Across all trials, mean age was 70.8, 58.5% were male, baseline NIHSS was mean 7.0, and time from last known well to treatment start was mean 148 mins. All ALT patients received standard 0.9 mg/kg dosing, while TNK dosing was 0.1 mg/kg in 6.8%, 0.25 mg/kg in 24.6%, and 0.4 mg/kg in 68.6%. For the primary endpoint, rates of disability-free (mRS 0-1) 3m outcome were: TNK 57.9% vs ALT 55.4%, RR 1.06 (95%CI 0.98-1.16) (Figure). The lower 95%CI bound fell well within the 0.88 non-inferiority margin. Similar results were seen for the additional efficacy endpoints: functional independence (mRS 0-2): TNK 71.9% vs ALT 70.5%, RR 1.02 (95% CI 0.96-1.09); and mRS shift analysis. For safety endpoints, lower event rates reduced power, but point estimates were also consistent with non-inferiority: Symptomatic ICH - TNK 3% vs ALT 3%, RR 0.96 (95% CI 0.56-1.65). Death – TNK 7.6% vs ALT 8.1%, RR 0.86 (95% CI 0.62-1.21). Conclusion: Accumulated clinical trial evidence provides strong evidence indicating that TNK is non-inferior to ALT in the treatment of AIS. These findings provide formal support for the recent guideline recommendation to consider TNK an alternative to ALT.

Abstract TP418: Asymptomatic Hemorrhagic Infarction on 24-Hour CT Post Intravenous Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke Predicts Symptomatic Intracerebral Hemorrhage After Initiation of Antiplatelet Therapy

Background and Purpose: Predictors of symptomatic intracerebral hemorrhage (sICH) after intravenous alteplase in acute ischemic stroke (AIS) are well established however there is limited data on predictors of delayed sICH (d-sICH) (occurring &gt; 36 hours from alteplase) after initiation of antithrombotic therapy in these patients. We hypothesize that asymptomatic hemorrhagic infarction (HI) on 24-hour brain imaging predicts delayed sICH after initiation of antiplatelet therapy. Methods: We included consecutive patients who received intravenous alteplase for AIS over a 12-month period. All patients received brain imaging, either CT or MRI, approximately 24-hours post alteplase. Patients who were deceased or made comfort measures only or with lack of at least 48 hour follow-up, or those with parenchymal hematoma (PH) or sICH prior to antithrombotic therapy initiation were excluded. The primary outcome was delayed sICH defined using the modified SITS-MOST criteria. We compared demographic data, clinical risk factors, NIHSS score, pre-admission antithrombotic usage, and 24-hour imaging characteristics between the two groups (d-sICH vs. no d-sICH) using univariate and multivariable analyses (including variables with p&lt;0.1 on univariable models). Analysis was done using SPSS version 20.0 and p&lt;0.05 was considered significant. Results: We identified 263 patients who met the inclusion criteria; 51.3% were men and the mean age was70.9 years, 8 patients (3.0%) had d-sICH and 60 patients (22.8%) had asymptomatic HI on 24-hour brain imaging (CT or MRI). On univariate analyses, predictors of d-sICH were diabetes [50.0% (4/8) vs. 23.1% (59/255), p = 0.097} and asymptomatic HI on CT [50.0% (4/8) vs. 13.1 (31/236), p=0.016] and a trend for asymptomatic hemorrhage on MRI [60.0% (3/5) vs. 25.0% (42/168), p = 0.11]. In a multivariable model, both diabetes (OR 5.1 95% CI 1.1 - 23.3, p=0.037) and asymptomatic hemorrhage on CT (OR 8.9 95% CI 1.9 - 41.7 p = 0.005) predicted d-sICH. Conclusion: In AIS patient receiving alteplase, asymptomatic HI on 24-hour brain imaging predicts d-sICH after antithrombotic treatment. Future studies are needed to confirm our findings and investigate best timing of initiating antiplatelet therapy and other measures to reduce d-sICH risk.

Low-dose versus standard-dose intravenous alteplase for octogenerian acute ischemic stroke patients: A multicenter prospective cohort study

Background and purposeThe optimal dose of alteplase for acute ischemic stroke among geriatric patients is unclear. We aimed to assess the efficacy and safety of a low-dose (0.6 mg/kg) and standard-dose (0.9 mg/kg) alteplase for varying severity of Asian geriatric stroke patients. MethodsThe favorable functional outcome on day 90 after stroke onset, and the symptomatic intracranial hemorrhage (SICH) rate following 24–36 h of intravenous alteplase were measured. The baseline NIHSS of 4–8, 9–13, ≥14 were defined as mild, moderate, and high severity, respectively. ResultsTotally, 249 geriatric patients treated with low-dose (n = 108) and standard-dose (n = 141) alteplase. Compared to standard-dose alteplase, low-dose alteplase had decrease in favorable functional outcome (22.2% versus 34.8%), and no difference in SICH rates was observed. For mild severity patients, the mortality was significantly increased with standard-dose alteplase (the NNT/NNH = 22.9/8.0 for mild severity, the NNT/ NNH = 15.0/14.7 for moderate severity, and the NNT/NNH = 13.5/19.6 for high severity). ConclusionsStandard-dose and low-dose alteplase were comparable in reducing major disability, but low-dose alteplase for mild stroke showed much reduced mortality on day 90 for octogenarians.

Efficacy of Tirofiban Administered at Different Time Points after Intravenous Thrombolytic Therapy with Alteplase in Patients with Acute Ischemic Stroke

ObjectiveTo evaluate the efficacy of tirofiban administered at different time points within 24 hours of intravenous thrombolysis with alteplase in acute ischemic stroke. MethodsPatients who underwent intravenous thrombolysis with alteplase and fulfilled other inclusion criteria were randomly divided into 4 groups according to the time points of tirofiban administration: Group A (2 h), Group B (2-12 h), Group C (12-24 h), and Group D (control). The changes in National Institutes of Health Stroke Scale score, modified Rankin Scale score, and adverse events were analyzed. ResultsAt 7 ± 1 day, the efficacy in Group A was better than that in Group C (P = .006) and Group D (P = .001), but there was no significant difference in the efficacy between Groups A and B (P = .268). Similarly, at 14 ± 2 d, the efficacy in Group A was better than that in Group C (P = .026) and Group D (P = .001), but there was no significant difference in the efficacy between Groups A and B (P = .394). As evaluated by the modified Rankin Scale, the prognosis in Groups A, B, and C was better than that in Group D (P = .042, .008, .027, respectively), which was unrelated to the time points of tirofiban administration. There was no significant difference in the incidence of adverse events among the four groups. ConclusionsTirofiban combined with alteplase is effective and safe, and particularly beneficial when administered at 2 hour and 2-12 hours after intravenous thrombolysis with alteplase in acute ischemic stroke.

Different doses of tenecteplase vs alteplase in thrombolysis therapy of acute ischemic stroke: evidence from randomized controlled trials.

BackgroundRecent studies showed inconsistent results of tenecteplase vs alteplase for acute ischemic stroke (AIS) with safety and efficacy.MethodsA meta-analysis was performed to explore the value of tenecteplase and alteplase in AIS treatment. Medline, Embase, and Cochrane Library from January 2001 to April 2018 were searched for randomized controlled trials (RCTs) with tenecteplase vs alteplase for AIS.ResultsThe primary outcomes were early neurological improvement at 24 h and functional outcome at 3 months. We pooled 1,390 patients from four RCTs. Tenecteplase showed a significant early neurological improvement (P=0.035) compared with alteplase. In addition, tenecteplase showed a neutral effect on excellent outcome (P=0.309), good functional outcome (P=0.275), and recanalization (P=0.3). No significant differences in safety outcomes were demonstrated. In subgroup analysis, 0.25 mg/kg dose of tenecteplase showed a significantly increased early neurological improvement (P<0.001). In serious stroke at baseline (National Institutes of Health Stroke Scale [NIHSS] >12) subgroup, tenecteplase showed a dramatic early neurological improvement (P=0.002) and low risks of any intracranial hemorrhage (ICH) (P=0.027).ConclusionTenecteplase provided better early neurological improvement than alteplase. The 0.25 mg/kg dose of tenecteplase subgroup specially showed better early neurological improvement and lower any ICH tendency than that of alteplase. In addition, in serious stroke at baseline subgroup, tenecteplase showed a lower risk of any ICH.

Impaired fasting glucose is associated with unfavorable outcome in ischemic stroke patients treated with intravenous alteplase.

Hyperglycemia on admission and diabetes mellitus type II are associated with unfavorable outcome in stroke patients. We studied whether impaired fasting glucose (IFG) is associated with unfavorable outcome in ischemic stroke patients treated with intravenous alteplase as well and if IFG is a stronger prognostic factor than hyperglycemia on admission. We studied 220 consecutive patients with ischemic stroke treated with intravenous alteplase. In all nondiabetic patients, fasting glucose was determined on day 2-5. IFG was defined as fasting glucose level of ≥ 5.6mmol/L, hyperglycemia on admission as glucose levels ≥ 7.9mmol/L. The primary effect measure was the adjusted common odds ratio (acOR) for a shift in the direction of worse outcome on the modified Rankin Scale at 3months, estimated with ordinal logistic regression, and adjusted for common prognostic factors. The fasting glucose levels were available in 194 and admission glucose levels in 215 patients. Sixty-three (32.5%) had IFG, 58 (27%) hyperglycemia on admission and 32 (14.6%) pre-existent diabetes. Patients with IFG showed a shift towards worse functional outcome compared with patients with normal fasting glucose levels (acOR 2.77; 95% CI 1.54-4.97), which was stronger than hyperglycemia on admission (acOR 1.75; 95% CI 0.91-3.4). IFG is associated with unfavorable outcome after treatment with intravenous alteplase for acute ischemic stroke. IFG predicts unfavorable outcome better than hyperglycemia on admission.