Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes with Alteplase at 0.6 mg/kg in Clinical Practice: THAWS2 Study.

INTRODUCTION: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. METHODS: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0-1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0-1 at 90 days, and change in NIHSS at 24 h from baseline. RESULTS: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75-16.25) at baseline to 5 (3-12.25) at 24 h after alteplase initiation (change, -4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of -8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. CONCLUSIONS: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them.

Safety and Efficacy of Intravenous Low-Dose Alteplase in Relative Contraindication Patients with Acute Ischemic Stroke.

OBJECT: The purpose of this study was to investigate the safety and efficacy of intravenous low-dose alteplase for acute ischemic stroke patients with relative contraindications. METHODS: The consecutive series of patients admitted within 4.5 hours of ischemic stroke onset between September 2012 and April 2017 were retrospectively evaluated. A good outcome at 90 days and symptomatic intracerebral hemorrhage were evaluated to determine the association with intravenous low-dose alteplase, especially in the presence of relative contraindications. RESULTS: Intravenous low-dose alteplase was administered to 219 of 315 patients (70%). A significantly higher number of patients treated with intravenous low-dose alteplase achieved a good outcome compared with those treated without alteplase (60% versus 44%; P = .014). The incidence of symptomatic intracerebral hemorrhage was not significantly different between the treatment groups. Multivariable logistic regression analysis of good outcome revealed that the significant independent factors were age of 81 years or older (odds ratio, .33; 95% confidence interval, .18-.60), National Institutes of Health Stroke Scale (NIHSS) of 4 or less (compared with NIHSS, 5-25; odds ratio, 3.3; 95% confidence interval, 1.8-6.4), modified Rankin scale score of 1 before stroke (odds ratio, .32; 95% confidence interval, .14-.73), and large changes on first brain imaging (odds ratio, .16; 95% confidence interval, .058-.44). Even with these relative contraindications, intravenous low-dose alteplase was still associated with good outcome (odds ratio, 3.1; 95% confidence interval, 1.6-5.8). CONCLUSIONS: Intravenous low-dose alteplase treatment can be safe and effective in relative contraindication patients with acute ischemic stroke.

Safety outcomes of early initiation of antithrombotic agents within 24 h after intravenous alteplase at 0.6 mg/kg.

BACKGROUND: We examined outcome of acute ischemic stroke (AIS) with administration of antithrombotics within 24 h after intravenous low-dose alteplase. METHODS: Consecutive AIS patients who were treated with intravenous alteplase at 0.6 mg/kg from 2005 to 2021 were retrospectively included in our single-center registry. Patients were classified into two groups: those who received antithrombotics within 24 h after intravenous alteplase (early initiation group) and those who did not (control group). Safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH (sICH) within 36 h after onset, and death within 3 months. sICH was defined as any ICH with a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score or death within 36 h. RESULTS: Of 1111 patients (women, 426; median age, 76 [interquartile range, 69-83] years; median NIHSS score, 11 [6-19]; cardioembolism, 580 [52.2%]), early initiation group comprised 58 patients (22; 72 [65-80] years; 7 [4-12]; 11 [19.0%]) and control group comprised 1053 patients (404; 77 [69-84] years; 11 [6-19]; 569 [54.1%]). No significant between-group differences were observed in the incidence of any ICH (17.2% vs. 21.6%; adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 0.57-2.44), sICH (0% vs. 0.9%, P = 1.00), or death within 3 months (5.2% vs. 6.7%; aOR, 1.23; 95% CI, 0.36-4.23). CONCLUSIONS: Early initiation of antithrombotics after intravenous alteplase at 0.6 mg/kg did not increase the rate of sICH or death within 3 months and may be used with caution in patients with advanced neurological deterioration.

Low-Dose Alteplase versus Conventional Anticoagulation to treat Submassive Pulmonary Embolism in Hispanic Patients.

The use of low-dose tissue plasminogen activator (tPA) in Hispanic patients with submassive pulmonary embolism (PE) is understudied. The purpose of this study is to explore the use of low-dose tPA in Hispanic patients with submissive PE compared with counterparts that received heparin alone. We retrospectively analyzed a single-center registry of patients with acute PE between 2016 and 2022. Out of 72 patients admitted for acute PE and cor pulmonale, we identified six patients that were treated with conventional anticoagulation (heparin alone) and six patients who received low-dose tPA (and heparin afterward). We analyzed if low-dose tPA was associated with differences in length of stay (LOS) and bleeding complications. Both groups were similar in regard to age, gender, and PE severity (based on Pulmonary Embolism Severity Index scores). Mean total LOS for the low-dose tPA group was 5.3 days, compared with 7.3 days in the heparin group ( p = 0.29). Mean intensive care unit (ICU) LOS for the low-dose tPA group was 1.3 days compared with 3 days in the heparin group ( p = 0.035). There were no clinically relevant bleeding complications documented in either the heparin or the low-dose tPA group. Low-dose tPA for submassive PE in Hispanic patients was associated with a shorter ICU LOS without a significant increase in bleeding risk. Low-dose tPA appears to be a reasonable treatment option in Hispanic patients with submassive PE who are not at high bleeding risk (<5%).

Intravenous Thrombolysis With Alteplase at 0.6 mg/kg in Patients With Ischemic Stroke Taking Direct Oral Anticoagulants.

Background We elucidated the safety of treatment with alteplase at 0.6 mg/kg within 24 hours for patients on direct oral anticoagulants (DOACs) before ischemic stroke onset. Methods and Results Consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis using alteplase at 0.6 mg/kg from 2011 to 2021 were enrolled from our single-center prospective stroke registry. We compared outcomes between patients taking DOACs and those not taking oral anticoagulants within 48 hours of stroke onset. The primary safety outcome was the rate of symptomatic intracranial hemorrhage with a ≥4-point increase on the National Institutes of Health Stroke Scale score from baseline. The efficacy outcome was defined as 3-month modified Rankin Scale score of 0 to 2 after stroke onset. Of 915 patients with acute ischemic stroke who received intravenous thrombolysis (358 women; median age, 76 years; median National Institutes of Health Stroke Scale score, 10), 40 patients took DOACs (6 took dabigatran, 8 took rivaroxaban, 16 took apixaban, and 10 took edoxaban) within 24 hours of onset and 753 patients did not take any oral anticoagulants. The rate of symptomatic intracranial hemorrhage was comparable between patients on DOACs and those not on oral anticoagulants (2.5% versus 2.4%, P=0.95). The rate of favorable outcomes was comparable between the 2 groups (59.4% versus 58.2%, P=0.46), although the admission National Institutes of Health Stroke Scale score was higher in patients on DOACs. No significant differences showed in any intracranial hemorrhage within 36 hours or mortality at 3 months. Conclusions Intravenous thrombolysis would be safely performed for patients on DOACs following the recommendations of the Japanese guidelines. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02251665.

Low-cost alternatives for the management of acute ischemic stroke in low and middle-income countries.

Acute ischemic stroke (AIS) patients arriving within a suitable time frame are treated with recanalization therapy i.e. intravenous thrombolysis (IVT) with alteplase and/or mechanical thrombectomy (MT). IVT with alteplase is indicated in AIS patients presenting within 4.5 hours of onset regardless of vascular territory involved. MT is indicated in AIS patients presenting within 24 hours of onset with large vessel occlusion in the anterior circulation. However, MT is ludicrously expensive and requires exorbitant setup, devices, and expertise which is not currently feasible in LMICs. Therefore, in LMICs the only feasible recanalization option left for AIS patients is IVT. The cost of IVT varies across the LMICs, however, most of them cost around 2000-5000 USD. Apart from IVT, patients with AIS often have other significant medical costs including those for neuroimaging, intensive care, and prolonged rehabilitative treatment. In LMICs, these costs can only be afforded by a handful of patients. The majority of the LMICs have health insurance in their infancy and family members of AIS patients opt-out IVT due to the economic burden. In general, the current treatment guidelines for AIS are not very useful in LMICs because of cost-related issues among several other factors. In this editorial, we discuss evidence for alternative treatment strategies that can help tackle the rising epidemic of AIS in poor countries by improvising on existing clinical guidelines and seeking alternative treatment regimens.