Dose Of Alteplase Research Articles

The outcomes of mechanical thrombectomy in patients with acute stroke with and without intravenous injection of tissue plasminogen activator

Background: Stroke is a major health problem and leading cause of mortality worldwide. This study aimed to evaluate the consequences of intravascular interventions in patients with acute ischemic stroke with and without intravenous tissue plasminogen activator (tPA) injection. Methods: This prospective cohort study was conducted on 120 patients with acute ischemic stroke. Patients were divided into three groups based on the type of disease treatment: angiography, tPA, and combined therapy (angiography + tPA). Patients in the tPA group were treated with a standard dose of intravenous alteplase (0.9 mg/kg). The severity of acute ischemic stroke was calculated on days 0, 14, and 90 after the interventions using the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) questionnaires. Results: All three groups were homogeneous regarding age, gender, location, job status, education, and body mass index (BMI) distribution. Coronary disease was the most common risk factor for stroke in 38.33% of patients. There was no significant difference in mean NIHSS and mRS scores between the groups on days 0, 14, and 90 after intervention (p > 0.05). Mean NIHSS and mRS scores significantly decreased from the first time point (day 0), 10 days until 90 days after treatment in all three groups (p < 0.001); however, there was no significant difference in treatment effect between the three groups at these time points (p > 0.05). Conclusion: Treatment with angiography and tPA alone or with combined therapy significantly decreased the severity of acute ischemic stroke. A significant decrease was observed in the mean NIHSS and mRS scores in all therapy groups, indicating that these treatments were effective in mitigating acute ischemic stroke and improving functional independence in these patients. The eligibility criteria by which patients with acute ischemic stroke are selected for each specific therapy are essential to achieving better clinical outcomes.

Effectiveness of alteplase infusion for the management of prosthetic mitral valve thrombosis in paediatric age group and proposed algorithm.

The incidence of prosthetic valve implantation is increasing in the paediatric population. Prosthetic valve thrombosis leading to obstruction could potentially be a life-threatening complication. There is a debate regarding optimal management of this complication, and there is limited use of thrombolytic therapy in childhood in the setting of valve thrombosis. We aim to share our experience of successfully using fibrinolytic therapy in terms of alteplase for paediatric prosthetic mitral valve thrombosis and to propose a management algorithm. This retrospective analysis of the database was conducted at our hospital including patients who underwent thrombolysis (alteplase) for prosthetic mitral valve thrombosis from June, 2011 to June, 2021. A total of 10 patients with 20 attempts of alteplase infusion were found in our record. Alteplase was successful in 19 attempts to relieve valve thrombosis. The safe and effective dose of alteplase was between 0.1 and 0.3 mg/kg/hour. There were no associated major bleeding complications and alteplase was administered either by central or peripheral line. Thrombolysis by alteplase infusion was found to be successful in relief of prosthetic mitral valve thrombosis in paediatric population without major bleeding complications.

TPA or not tPA? Lysis therapy in the setting of COVID‐19 and ECMO

We read with interest the recent article entitled, “Using lysis therapy to treat five critically ill COVID-19 patients who show echocardiographic criteria of right ventricular strain” by Mahdy et al., which described five patients who underwent lysis therapy for COVID-19-associated critical illness with respiratory failure and right heart strain. We find this topic especially relevant in the context of the global COVID-19 pandemic, which has now claimed over 800,000 American lives and over 1.5 million worldwide. Critical illness secondary to COVID-19 is associated with an inflammatory state and coagulopathy; the mechanisms underlying this state are still under investigation [1-4]. There are multiple case reports describing adverse thrombotic events in this population [1-4] and we are particularly interested in the authors’ report of Patient 5, who was receiving extracorporeal membranous oxygenation (ECMO) at the time of lysis therapy. ECMO generally requires systemic anticoagulation due to a hypercoagulable state induced by contact of the patient's blood with the cannulas, but the choice of medication and the intensity of therapy vary in different settings and in patients with different medical conditions. The increased volume of distribution caused by the circuit also calls the standard dosing of alteplase into question. The balance between thrombotic events and bleeding complications is a delicate one without even accounting for the coagulopathy associated with COVID-19. Recently, we provided veno-venous ECMO for a 47-year-old man with severe hypoxemia secondary to acute respiratory distress syndrome (ARDS) associated with COVID-19 pneumonia. His hypoxemia was refractory to mechanical ventilation, neuromuscular blockade, and prone positioning. In addition, the patient had completed a course of dexamethasone and remdesivir as targeted therapy for COVID-19. His medical history was significant for obesity, congenital solitary kidney, hypothyroidism, and hyperlipidemia. While on ECMO, he received therapeutic anticoagulation with unfractionated heparin. On hospital day 17 (ICU day 13 and day 21 since symptom onset), our patient developed a massive pulmonary embolism with acute right ventricle (RV) failure (Figure 1). The patient's coagulation parameters on this day were as follows: PTT 102.3 s, INR 2, d-dimer 85,940 FEU. He was too hemodynamically unstable to transfer for thrombectomy. After a multidisciplinary discussion, we gave intravenous alteplase (10 mg bolus over 1 min followed by 90 mg infusion over 2 h). Within minutes, he stabilized and there were no associated bleeding complications. Anticoagulation decreases mortality in COVID-19-associated critical illness and is recommended while patients are on ECMO [2-4], but studies reporting thrombotic complications despite therapeutic heparin are common [5]. The ideal anticoagulation strategy for these patients is still unclear. Prior to the pandemic, there were scant reports on the use of thrombolytics while on ECMO, leaving little guidance for clinicians at the bedside. We are curious if the authors of this case series are able to report more on Patient 5's coagulation studies, how they chose their alteplase dose, their consideration of bleeding risks, and if they have other recommendations for clinicians considering lytic therapy for patients with COVID-19 disease requiring veno-venous ECMO. We are grateful to the patient described here, and to the patient's family who consented to the publication of this report. The authors declare no conflict of interest. The authors received no specific funding for this work.

Tenecteplase versus alteplase for the management of acute ischaemic stroke in Norway (NOR-TEST 2, part A): a phase 3, randomised, open-label, blinded endpoint, non-inferiority trial

Tenecteplase is a modified tissue plasminogen activator with pharmacological and practical advantages over alteplase-which is currently the only approved thrombolytic drug for ischaemic stroke. The NOR-TEST trial showed that 0·4 mg/kg tenecteplase had an efficacy and safety profile similar to that of a standard dose (0·9 mg/kg) of alteplase, albeit in a patient population with a high prevalence of minor stroke. The aim of NOR-TEST 2 was to establish the non-inferiority of tenecteplase 0·4 mg/kg to alteplase 0·9 mg/kg for patients with moderate or severe ischaemic stroke. This phase 3, randomised, open-label, blinded endpoint, non-inferiority trial was performed at 11 hospitals with stroke units in Norway. Patients with suspected acute ischaemic stroke with a National Institutes of Health Stroke Scale score of 6 or more who were eligible for thrombolysis and admitted within 4·5 h of symptom onset were consecutively included. Random assignment, done by a computer with a block size of 4 and with allocations placed into opaque envelopes to be opened consecutively, was 1:1 between intravenous tenecteplase (0·4 mg/kg) or standard dose alteplase (0·9 mg/kg). Doctors and nurses providing acute care were not masked to treatment, but primary outcome assessment at 3 months was masked. The primary outcome was favourable functional outcome defined as a modified Rankin Scale score of 0-1 at 3 months, assessed in the modified intention-to-treat analysis (excluding patients who did not qualify for thrombolysis after randomisation or who withdrew informed consent). The non-inferiority margin was 3%. This trial (NOR-TEST 2) is registered with EudraCT (number 2018-003090-95) and ClinicalTrials.gov (NCT03854500). The trial was stopped early for safety reasons and is designated part A for analysis. Part B is ongoing with a lower dose of tenecteplase (0·25 mg/kg). Between Oct 28, 2019, and Sept 26, 2021, 216 patients were enrolled. Patient enrolment was stopped after a per-protocol safety review showed an imbalance in the rates of symptomatic intracranial haemorrhage between the treatment groups, which surpassed the prespecified criteria for stopping the trial. Of 204 patients entering the modified intention-to-treat analysis, 100 were randomly allocated tenecteplase and 104 were allocated alteplase. All patients were followed up within 14 days of the end of the 3-months' follow-up period. A favourable functional outcome was reported less frequently in patients receiving tenecteplase (31 [32%] of 96 patients) compared with alteplase (52 [51%] of 101 patients; unadjusted OR 0·45 [95% CI 0·25-0·80]; p=0·0064). Any intracranial haemorrhage was significantly more frequent with tenecteplase (21 [21%] of 100 patients) than with alteplase (seven [7%] of 104 patients; unadjusted OR 3·68 [95% CI 1·49-9·11]; p=0·0031). Mortality at 3 months was also significantly higher with tenecteplase (15 [16%] of 96 patients) than with alteplase (five [5%] of 101 patients; unadjusted OR 3·56 [95% CI 1·24-10·21]; p=0·013). Numerically more cases of symptomatic intracranial haemorrhage were reported with tenecteplase (six [6%] of 100 patients) than with alteplase (one [1%] of 104 patients; unadjusted OR 6·57 [95% CI 0·78-55·62]; p=0·061). In this prematurely terminated study (terminated to fulfil the prespecified safety criteria), tenecteplase at a dose of 0·4 mg/kg yielded worse safety and functional outcomes compared with alteplase. Our study consequently could not show that 0·4 mg/kg tenecteplase is non-inferior to alteplase in moderate and severe ischaemic stroke. Future stroke trials should assess a lower dose of tenecteplase versus alteplase in patients with moderate or severe stroke. The Norwegian National Programme for Clinical Therapy Research.

Post-thrombolytic coagulopathy and complications in patients with pulmonary embolism treated with fixed-dose systemic alteplase

Alteplase treatment can cause a systemic coagulopathy although the incidence and contributory factors are unknown in pulmonary embolism (PE). Fixed-dosing of alteplase for PE may lead to interpatient variability in drug exposure and influence post-thrombolytic coagulopathy (PTC). While changes in fibrinogen and INR have been used to describe PTC, no universal PTC definition is available. Evaluate the incidence of PTC after alteplase treatment for PE, the effect of patient weight and blood/plasma volume and the association with bleeding complications. We conducted a retrospective cohort study of patients treated with alteplase for massive or high-risk submassive PE. Demographics, alteplase dosing, laboratory assessment of coagulopathy, and bleeding events were collected. The primary endpoint was incidence of PTC defined as an international normalized ratio (INR) > 1.5 or fibrinogen < 170mg/dL. Secondary outcomes included correlation between coagulopathies and alteplase dose normalized to actual body weight (ABW), ideal body weight (IBW), plasma volume (PV), and estimated blood volume (EBV). Bleeding events in patients with and without PTC were compared. 125 patients met criteria for inclusion in the study. PTC occurred in 35.3% of patients, with INR >1.5 in 21.8% and fibrinogen <170mg/dL in 26%. Alteplase dose >50mg was associated with increased odds of PTC (OR 6.5, CI 2.1-19.9). Dose normalized to ABW and EBV correlated weakly with absolute increase in post-alteplase INR (r =0.20, p =0.06 and r =0.21, p =0.057 respectively) and to percent change in INR (r =0.20, p = 0.058 and r =0.21, p =0.048 respectively). Dose/ABW, dose/PV, and dose/EBV each correlated moderately with absolute decrease in fibrinogen (r =-0.53, -0.49, and -0.47 respectively, p <0.001 for each) and percent change in fibrinogen (r = -0.55, -0.49, and -0.49 respectively, p < 0.001 for each). Dose/IBW correlated weakly with absolute and percent decrease in fibrinogen (r = -0.32, p =0.013 and r =-0.33, p =0.011). Patients with bleeding were more likely to have PTC (58.3% vs. 28.6%, p= 0.05) and a bleeding event was predictive of PTC (OR 5.33, 1.32-23.99). PTC is prevalent in patients with PE. PTC is influenced by alteplase dose and exposure parameters (ABW, IBW, PV, EBV) and may contribute to the bleeding risk.

Catheter-directed thrombolysis in acute critical limb ischemia

Acute limb ischemia has great clinical significance due to its common occurrence and serious complications. Besides open surgical intervention, catheter-directed thrombolysis is a proven treatment alternative, however, it is not widely used in Hungary. To evaluate the efficacy and safety of catheter-directed thrombolysis in acute limb ischemia. In a retrospective single-center study, we analyzed the data of 40 patients (mean age: 64, SD: ±11.79; 25 men, 69.57%) who underwent catheter-directed thrombolysis due to acute limb ischemia at Semmelweis University Heart and Vascular Centre between 01. 03. 2012 and 31. 12. 2019. 42 thrombolysis were performed on 40 patients. The median alteplase dose was 5 mg (IQR: 5), the median continuous dose was 2 mg/h (IQR: 0.8). 23 (54.76%) procedures were successful and 16 (69.57%) cases required further percutaneous interventions. Hemorrhage led to 5 and occlusion to 3 emergency interventions. The most common postoperative complications were amputation (17.5%), hematoma (11.9%) and distal embolisation (7.14%). 16 (40%) cases required late reintervention at the surgical site. 11 (27.5%) cases needed major amputation. 30 day postoperative mortality was 2.5%. Average intervention-free survival was 1626 days (SD: ±1710), while average amputation-free survival was 2038 days (SD: ±1665). Additional intravenous heparin given during thrombolysis did not affect reocclusion rate and amputation-free survival. Catheter-directed thrombolysis is a therapeutic option in acute limb ischemia. Successful thrombolysis often requires endovascular intervention at the same time. Frequent early complications and late reinterventions have to be considered. Further studies are needed for developing specific therapeutic protocol. Orv Hetil. 2022; 163(11): 424-430.

Comparison of Different Dosages of Alteplase in Atrial Fibrillation-Related Acute Ischemic Stroke After Intravenous Thrombolysis: A Nationwide, Multicenter, Prospective Cohort Study in Taiwan.

BackgroundInsufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses.Methods and ResultsThis multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk‐scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non‐AF group, the AF group exhibited a 2‐ to 3‐fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk [RR], 2.10 [95% CI, 1.35–3.26]). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke‐Monitoring Study standards did not significantly differ between the AF and non‐AF groups. In addition, the low‐dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 [95% CI, 1.63–4.96]). A validation study confirmed these findings after adjustment for scores determined using different stroke risk‐scoring tools.ConclusionsDifferent alteplase dosages did not affect functional status at 90 days in the AF and non‐AF groups. Thus, the adoption of low‐dose alteplase simply because of AF is not recommended.

Safety and Effectiveness of Lower Alteplase Dose Driven by Impending Clinical Deterioration Factors in very Elderly Submassive Pulmonary Embolism Patients. Case Series

Although thrombolysis improves the outcome and mortality in submassive (SM) and massive PE, its role is controversial because of the high rate of intracranial hemorrhage. In addition, safety and efficacy are unclear since randomized controlled studies have excluded very elderly patients because of frailty, multiple comorbidities, and a higher risk of bleeding. Therefore, the best thrombolytic regimen is unknown. Furthermore, it is unclear whether the decision-making for thrombolysis is performed according to the guidelines or based on clinical risk factors associated with poor outcomes. We report three very elderly SMPE associated with several impending clinical deterioration factors (ICDF) (in-transit thrombus, saddle thrombus, etc.). Therefore, we decided on 25 mg alteplase in one- or two-hour continuous infusion based on ICDF rather than clinical instability and systolic hypotension. In addition, we initiate DOACs around 48 hours after stopping unfractionated heparin (UFH). As a result, all patients improve right ventricular performance without bleeding complications. Our results suggest that the lower alteplase dose in one- or two-hour continuous infusion, followed by weight-adjusted UFH, was effective and safe, involving a complicated scenario as an intransit thrombus. Also, DOACs standard doses driven by the patient´s characteristics were unrelated to bleeding complications avoiding recurrence in very elderly SMPE.

Outcomes of stroke patients undergoing thrombolysis in Sri Lanka; an observational prospective study from a low-middle income country

BackgroundStroke related deaths are relatively higher in low- and middle-income countries where only a fraction of eligible patients undergo thrombolysis. There is also limited evidence on post-thrombolysis outcomes of patients from Asian countries in these income bands.MethodsThis is a single center prospective observational study of a patient cohort with acute ischaemic stroke, undergoing thrombolysis with alteplase (low and standard dose), over a 24-month period in 2019/2020. Modified Rankin scale (mRS) for dependency at 3 months (primary outcome), duration of hospital stay, incidence of symptomatic intracranial haemorrhages and all-cause mortality at 3 months (secondary outcomes) were recorded. Demographic, clinical and treatment related factors associated with these outcomes were explored.ResultsEighty-nine patients (males – 61, 69%, mean age: 60 years ±12.18) were recruited. Time from symptom onset to reperfusion was 174 min ± 56.50. Fifty-one patients were independent according to mRS, 11 (12.4%) patients died, and 11 (12.5%) developed symptomatic intracranial haemorrhages by 3 months. Functional independence at 3 months was independently associated with National Institutes of Health Stroke Scale (NIHSS) on admission (p < 0.05). Thrombolysis with low dose alteplase did not lead to better or worse outcomes compared to standard dose.ConclusionsOn admission NIHSS is predictive of functional independence at 3 months post-thrombolysis. Low dose alteplase may be as efficacious as standard dose alteplase with associated cost savings, but this needs to be confirmed by a prospective clinical trial for the Sri Lankan population.

Predictors of mortality in patients with intermediate risk pulmonary embolism

Abstract Introduction Information about treatment and outcome of patients with pulmonary embolism (PE) intermediate risk remains limited. Little is known about the benefits of reperfusion therapy in patients with intermediate risk PE and evidence of right ventricular dysfunction. Objective To evaluate clinical outcomes and predictors of mortality in patients admitted to ICU with pulmonary embolism and intermediate risk. Methods In a prospective single-center study 103 normotensive patients with an established diagnosis of pulmonary embolism confirmed by pulmonary CT were included. All patients met intermediate risk criteria according to the European Society of Cardiology guidelines (ESC 2019) for pulmonary embolism using severity index [PESI] with signs of right ventricular dysfunction and elevated cardiac biomarkers. The average age of patients was 67.6 years (95% CI, 65.1–70.5), 42 (41%) of them were men. Thrombolysis with standard dose of alteplase was performed in 54 (52%) patients. CT scan and echocardiography were done for all patients. Results Outcome data were collected for all patients through the 30-day and 180-day follow-up. During 30 days follow up 14 patients died (13,6%, 95% CI, 6,9–20%). The all-cause mortality rate after 180 days was 22,2% (95% CI, 13,5–31%) - 22 patient. In the thrombolysis group only 2 patients died after 180-day follow-up, mortality rate was 4,4% (95% CI, 1,7–10,6%), the mortality rate in patients not treated by thrombolysis was 40% (95% CI, 25,3–54,7%). Thrombolysis was associated with a significant decrease in mortality [OR 0.07 (95% CI, 0.01–0.31)]. In the thrombolysis group 2 patients (4.1%; 95% CI, 1.1–10%) had a non-fatal major bleeding event. The presence of chronic heart failure [OR 6 (95% CI, 1.8–20.2)] and previous stroke [OR 4.3 (95% CI, 0.9–21.1)] were higher among non-survivors when compared to survivors (p≤0.05). TAPSE less than 16 mm was found to be negatively associated with survival [OR 5.5 (95% CI, 0.9–40.3)], p=0.02. Conclusion In our study thrombolysis in patients with pulmonary embolism and intermediate-risk was associated with improved prognosis. Predictors of mortality were the presence of CHF, previous stroke and TAPSE of less than 16 mm. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier mortality curves. p&amp;lt;0.05

Low-dose versus standard-dose alteplase for intravenous thrombolysis in patients with acute ischemic stroke in Iran: Results from the safe implementation of treatments in stroke registry

Background: Rates of intracranial hemorrhage (ICH) after intravenous thrombolysis (IVT) differ depending on ethnicity, one reason that few Eastern countries have approved a lower dose of alteplase. Data in this regard are scarce in the Middle Eastern region. Methods: The present retrospective study was performed on data extracted from the Safe Implementation of Treatments in Stroke (SITS) registry. Computed tomography (CT) image analysis was based on the SITS-Monitoring Study (SITS-MOST) definition for symptomatic ICH (SICH). Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS). Multivariate logistic regression including adjusted analysis was used for comparison between groups. Results: Of 6615 patients, 1055 were enrolled. A total of 86% (n = 906) received a standard dose and 14% (n = 149) received a low dose of alteplase. Favorable 3-month outcome was achieved in 481 (53%) patients in the standard group and 71 (48%) patients in the low-dose group [adjusted odds ratio (AOR) = 1.24, 95% confidence interval (CI): 0.87-1.75, P = 0.218]. SICH occurred in 14 (1.5%) patients in the standard group and 3 (2%) patients in the low-dose group [odds ratio (OR) = 2.77, 95% CI: 0.36-21.04, P = 0.120]. At 3 months, mortality occurred in 145 (16.0%) patients in the standard group and 29 (19.4%) patients in the low-dose group (OR = 1.22, 95% CI: 0.78-1.91, P = 0.346). Conclusion: Low-dose compared to standard-dose alteplase for patients with acute ischemic stroke (AIS) was not associated with fewer hemorrhagic events and there was no significant difference in the favorable 3-month outcome (mRS: 0-2) or mortality rate.

Stability of alteplase for ultrasound-facilitated catheter-directed thrombolysis

AbstractUltrasound-facilitated catheter-directed thrombolysis is used with low-dose alteplase to treat pulmonary embolism. This reduces the risk of bleeding that accompanies systemic administration of higher alteplase doses. Some studies suggest that alteplase given over 2 to 6 hours is safe and effective, but there are few data to support the stability of alteplase under these conditions. Therefore, we undertook this in vitro study to determine the duration of alteplase stability. Alteplase was prepared in solutions of 8 mg in 100 mL, 6 mg in 150 mL, and 8 mg in 200 mL. Solutions were administered through the EkoSonic Endovascular System (with and without ultrasound) to simulate administration over 2, 4, and 6 hours. Alteplase was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). Assays were performed at time 0 and at 30-minute intervals during simulated infusion. An enzyme-linked immunosorbent assay was used to measure alteplase concentrations at time 0 and at 15-minute intervals during simulated infusion. By using RP-HPLC in the absence of ultrasound, the alteplase concentration remained within 1% of the original concentration through 120, 240, and 360 minutes of infusion. By using RP-HPLC for measurement, alteplase in the presence of ultrasound degraded steadily over time to ∼90% of its original amount in 120 minutes, ∼80% in 240 minutes, and ∼70% in 360 minutes. The remaining alteplase was available for enzymatic activity. Alteplase solutions of 0.04 and 0.08 mg/mL degraded steadily over time during simulated ultrasound-facilitated catheter-directed administration. Alteplase that did not degrade remained available for enzymatic activity.

Early decompressive hemicraniectomy in thrombolyzed acute ischemic stroke patients from the international ENCHANTED trial

Decompressive hemicraniectomy (DHC) can improve outcomes for patients with severe forms of acute ischemic stroke (AIS), but the evidence is mainly derived from non-thrombolyzed patients. We aimed to determine the characteristics and outcomes of early DHC in thrombolyzed AIS participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international, partial-factorial, open, blinded outcome-assessed, controlled trial in 4557 thrombolysis-eligible AIS patients randomized to low- versus standard-dose intravenous alteplase (Arm A, n = 2350), intensive versus guideline-recommended blood pressure control (Arm B, n = 1280), or both (Arms A + B, n = 947). Logistic regression models were used to identify baseline variables associated with DHC, with inverse probability of treatment weights employed to eliminate baseline imbalances between those with and without DHC. Logistic regression was also used to determine associations of DHC and clinical outcomes of death/disability, major disability, and death (defined by scores 2–6, 3–5, and 6, respectively, on the modified Rankin scale) at 90 days post-randomization. There were 95 (2.1%) thrombolyzed AIS patients who underwent DHC, who were significantly younger, of non-Asian ethnicity, and more likely to have had prior lipid-lowering treatment and severe neurological impairment from large vessel occlusion than other patients. DHC patients were more likely to receive other management interventions and have poor functional outcomes than non-DHC patients, with no relation to different doses of intravenous alteplase. Compared to other thrombolyzed AIS patients, those who received DHC had a poor prognosis from more severe disease despite intensive in-hospital management.

Institutional trends over a decade in catheter-directed interventions for pulmonary embolism

ObjectiveCatheter-directed interventions (CDIs) are commonly performed for acute pulmonary embolism (PE). The evolving catheter types and treatment algorithms impact the use and outcomes of these interventions. This study aimed to investigate the changes in CDI practice and their impact on outcomes. MethodsPatients who underwent CDIs for PE between 2010 and 2019 at a single institution were identified from a prospectively maintained database. A PE team was launched in 2012, and in 2014 was established as an official Pulmonary Embolism Response Team. CDI annual use trends and clinical failures were recorded. Clinical success was defined as physiologic improvement in the absence of major bleeding, perioperative stroke or other procedure-related adverse event, decompensation for submassive or persistent shock for massive PE, the need for surgical thromboembolectomy, or death. Major bleeding was defined as requiring a blood transfusion, a surgical intervention, or suffering from an intracranial hemorrhage. ResultsThere were 372 patients who underwent a CDI for acute PE during the study period with a mean age of 58.9 ± 15.4 years; there were males 187 (50.3%) and 340 patients has a submassive PE (91.4%). CDI showed a steep increase in the early Pulmonary Embolism Response Team years, peaking in 2016 with a subsequent decrease. Ultrasound-assisted thrombolysis was the predominant CDI technique peaking at 84% of all CDI in 2014. Suction thrombectomy use peaked at 15.2% of CDI in 2019. The mean alteplase dose with catheter thrombolysis techniques decreased from 26.8 ± 12.5 mg in 2013 to 13.9 ± 7.5 mg in 2019 (P < .001). The mean lysis time decreased from 17.2 ± 8.3 hours in 2013 to 11.3 ± 8.2 hours in 2019 (P < .001). Clinical success for the massive and the submassive PE cohorts was 58.1% and 91.2%, respectively; the major bleed rates were 25.0% and 5.3%. There were two major clinical success peaks, one in 2015 mirroring our technical learning curve and one in 2019 mirroring our patient selection learning curve. The clinical success decrease in 2018 was primarily derived from blood transfusions owing to acute blood loss during suction thrombectomy. ConclusionsCDIs for acute PE have rapidly evolved with high success rates. Multidisciplinary approaches among centers with appropriate expertise are advisable for the safe and successful implementation of catheter interventions.

Thrombolysis outcomes according to arterial characteristics of acute ischemic stroke by alteplase dose and blood pressure target.

We explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models. There were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56-2.90]) but comparable in MVO (1.34 [0.96-1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54-1.30]/0.48 [0.25-0.91]/0.99 [0.75-2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74-2.38]/0.78 [0.31-1.94]/1.24 [0.64-2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14-2.72]/0.17 [0.02-1.47]/2.69 [0.90-8.04], Pinteraction = 0.05). Functional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power.Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifiers: NCT01422616.

Disparities between Asian and Non-Asian Thrombolyzed Acute Ischemic Stroke Patients in the Enhanced Control of Hypertension and Thrombolysis Stroke Trial

Background and Purpose: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). Methods: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130–140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2–6), major disability (mRS 3–5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1–24 h. Results: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2–6 or 3–5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85–1.19 [p = 0.958] and OR 0.95, 95% CI 0.80–1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95–1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23–1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18–2.12; p = 0.002). Conclusions: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups.

Direct to Thrombectomy.

Direct to Thrombectomy.

Maximum intravenous alteplase dose for obese stroke patients is not associated with greater likelihood of worse outcomes

BackgroundIV alteplase is a primary treatment for acute ischemic stroke (AIS) at a weight-based dose (WBD) of 0.9 mg/kg and maximum dose (MD) of 90 mg. There are conflicting data regarding outcomes for those weighing ≥100 kg. There is also a paucity of data in Hispanics. The prevalence of adult obesity in the US has progressively increased; hence, the percentage of patients receiving the maximum dose also is expected to rise. We examined differences between patients treated with WBD vs. MD. MethodsA retrospective review of our center's Get With The Guidelines-Stroke database was performed for IV alteplase cases between October 2013–February 2017. Selection criteria included age ≥18 years, IV alteplase administration, and a recorded measured weight. Patients were dichotomized into WBD group weighing <100 kg and MD group weighing ≥100 kg. Categorical variables were analyzed using Chi square tests and continuous variables were analyzed using independent samples t-tests. Multivariable logistic regression analysis was performed to determine whether MD in combination with other variables was associated with poor outcomes. ResultsThere were 328 patients included in the study, 38 (11.6%) received MD. Proportions of younger, male, and non-Hispanic were higher in the MD group. There were no statistically significant differences for initial NIHSS, discharge modified Rankin Scale (mRS), 90-day mRS, symptomatic intracerebral hemorrhage (sICH), or systemic hemorrhage between groups. ConclusionOne in ten patients thrombolysed for the treatment of AIS received MD. In a predominantly Hispanic population, those who received MD and WBD had similar rates of sICH, discharge disposition, and functional outcome (mRS) at discharge and at 90 days. Limitations include small sample size and attrition for the 90-day mRS.

Randomized Trial Comparing Standard Versus Ultrasound-Assisted Thrombolysis for Submassive Pulmonary Embolism: TheSUNSET sPE Trial.

The aim of this trial was to determine whether ultrasound-assisted thrombolysis (USAT) is superior to standard catheter-directed thrombolysis (SCDT) in pulmonary arterial thrombus reduction for patients with submassive pulmonary embolism (sPE). Catheter-directed therapy has been increasingly used in sPE and massive pulmonary embolism as a decompensation prevention and potentially lifesaving procedure. It is unproved whether USAT is superior to SCDT using traditional multiple-side-hole catheters in the treatment of patients with pulmonary embolism. Adults with sPE were enrolled. Participants were randomized 1:1 to USAT or SCDT. The primary outcome was 48-hour clearance of pulmonary thrombus assessed by pre- and postprocedural computed tomographic angiography using a refined Miller score. Secondary outcomes included improvement in right ventricular-to-left ventricular ratio, intensive care unit and hospital stay, bleeding, and adverse events up to 90days. Eighty-one patients with acute sPE were randomized and were available for analysis. The mean total dose of alteplase for USAT was 19 ± 7mg and for SCDT was 18 ± 7mg (P=0.53), infused over 14 ± 6 and 14 ± 5 hours, respectively (P=0.99). In the USAT group, the mean raw pulmonary arterial thrombus score was reduced from 31 ± 4 at baseline to 22 ± 7 (P< 0.001). In the SCDT group, the score was reduced from 33 ± 4 to 23 ± 7 (P< 0.001). There was no significant difference in mean thrombus score reduction between the 2 groups (P=0.76). The mean reduction in right ventricular/left ventricular ratio from baseline (1.54 ± 0.30 for USAT, 1.69 ± 0.44 for SCDT) to 48 hours was 0.37 ± 0.34 in the USAT group and 0.59 ± 0.42 in the SCDT group (P=0.01). Major bleeding (1 stroke and 1 vaginal bleed requiring transfusion) occurred in 2 patients, both in the USAT group. In the SUNSET sPE (Standard vs. Ultrasound-Assisted Catheter Thrombolysis for Submassive Pulmonary Embolism) trial, patients undergoing USAT had similar pulmonary arterial thrombus reduction compared with those undergoing SCDT, using comparable mean lytic doses and durations of lysis.

Adjunctive Intra-arterial Thrombolysis in Endovascular Thrombectomy: A Systematic Review and Meta-analysis.

To evaluate the safety and efficacy of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in ischemic stroke, we performed a systematic review and meta-analysis of the literature. Searches were performed using MEDLINE, Embase, and Cochrane databases for studies that compared EVT with EVT with adjunctive IAT (EVT + IAT). Safety outcomes included symptomatic intracerebral hemorrhage and mortality at 3 months. Efficacy outcomes included successful reperfusion (Thrombolysis in Cerebral Infarction score of 2b-3) and functional independence, defined as a modified Rankin Scale score of 0-2 at 3 months. Five studies were identified that compared combined EVT + IAT (IA alteplase or urokinase) with EVT only and were included in the random-effects meta-analysis. There were 1693 EVT patients, including 269 patients treated with combined EVT + IAT and 1,424 patients receiving EVT only. Pooled analysis did not demonstrate any differences between EVT + IAT and EVT only in rates of symptomatic intracerebral hemorrhage (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.20-1.85; p = 0.78), mortality (OR: 0.77, 95% CI: 0.54-1.10; p = 0.15), or successful reperfusion (OR: 1.05, 95% CI: 0.52-2.15; p = 0.89). There was a higher rate of functional independence in patients treated with EVT + IAT, although this was not statistically significant (OR: 1.34, 95% CI: 1.00-1.80; p = 0.053). Adjunctive IAT appears to be safe. In specific situations, neurointerventionists may be justified in administering small doses of intra-arterial alteplase or urokinase as rescue therapy during EVT.