rt-PA Group Research Articles

Efficacy and safety of tirofiban plus recombinant tissue plasminogen activator versus recombinant tissue plasminogen activator alone in acute ischemic stroke patients: a meta-analysis

ObjectiveTirofiban plus recombinant tissue plasminogen activator (rtPA) shows good efficacy and safety in treating acute ischemic stroke (AIS) patients, but there is a lack of comprehensive assessment. This meta-analysis aimed to compare the efficacy and safety of rtPA plus tirofiban with rtPA alone in AIS patients. MethodsThis meta-analysis retrieved studies comparing rtPA intravenous thrombolysis followed by tirofiban (rtPA+T group) versus rtPA intravenous thrombolysis alone (rtPA group) for AIS patients in Excerpt Medica Database, Web of Science, Cochrane, PubMed, China National Knowledge Infrastructure, Wanfang, and SinoMed until March 2024. ResultsTwenty studies with 2048 AIS patients were enrolled in this meta-analysis. National Institute of Health stroke scale (NIHSS) score after treatment was lower in the rtPA+T group than the rtPA group [standardized mean differences (SMD)=-1.41; 95% confidence interval (CI)=-1.83, -0.98; P<0.001]. The proportion of AIS patients achieving a favorable functional outcome (modified Rankin Scale score ≤2) was increased in the rtPA+T group versus the rtPA group [relative risk (RR)=1.13; 95% CI=1.05, 1.21; P=0.001]. The incidence of re-occlusion was lower in the rtPA+T group than in the rtPA group (RR=0.24; 95% CI=0.10, 0.59; P=0.002), but the incidence of intracranial hemorrhage (ICH) (RR=0.85; 95% CI=0.51, 1.43), symptomatic ICH (RR=1.10; 95% CI=0.43, 2.84), and mortality (RR=1.39; 95% CI=0.53, 3.65) was not different between the two groups (all P>0.05). The stability assessed by sensitivity analysis was good, and no publication bias was found. ConclusionrtPA plus tirofiban achieves superior efficacy with comparable safety profiles compared to rtPA alone in AIS patients.

Predictors of hemorrhagic transformation in patients of first ever acute ischemic stroke receiving recombinant tissue plasminogen activator (rTPA)

Abstract Background Hemorrhagic transformation (HT) represents a serious complication of acute ischemic stroke (AIS). Aim To detect predictive factors linked to HT among patients having a first-ever AIS who received recombinant tissue plasminogen activator (rTPA), for better preselection of patients eligible for thrombolytic therapy. Patients and methods This research took place at the Neuropsychiatry Department and Centre of Psychiatry, Neurology, and Neurosurgery, Tanta University Hospitals over 12 months. The total number of patients included was 460, with 115 who received rTPA and 345 who did not receive rTPA. All participants underwent a comprehensive medical history, clinical and neurological assessments, radiological evaluation (ASPECT score), cardiac investigation, and were followed-up for two weeks to detect any HT. Results Patients with HT represented 21.7% of all rTPA patients, with symptomatic intracranial hemorrhage representing 6.9%, while non-rTPA patients with HT represented 13.9% and symptomatic intracranial hemorrhage represented 4.3%. HT patients in the rTPA group had significantly higher rates of smoking, respiratory rate, and lower platelet count, low density lipoprotein and cholesterol levels, while HT patients in the non-rTPA group exhibited significantly higher blood pressure, random blood sugar, as well as lower ASPECT scores. Conclusion There was an association between HT and five predictors (higher smoking rate, higher respiratory rate, lower platelet count, and lower low density lipoprotein and cholesterol levels) in first ever acute ischemic stroke patients receiving rTPA. In patients who did not receive rTPA, HT was associated with lower ASPECT scores, higher blood pressure, and random blood sugar.

Evaluation of demographic/clinical features and hemorrhagic complications in patients with ischemic stroke who underwent reperfusion therapy.

The relationship between demographic/clinical characteristics, clinical outcomes and the development of hemorrhagic complications in patients with ischemic stroke who underwent reperfusion therapy has not been studied sufficiently. We have aimed to compare genders and age groups in terms of clinical features and outcome; and types of reperfusion treatments and clinical features regarding the development of hemorrhagic complications in patients with ischemic stroke who underwent recombinant tissue plasminogen activator (rtPA) and/or thrombectomy. Patients with acute ischemic stroke undergoing rtPA and/or thrombectomy were divided into six age groups. Parameters including hemorrhagic complications, anticoagulant and antiaggregant use, hyperlipidemia, smoking status, biochemical parameters, and comorbidities were documented. National Institutes of Health Stroke Scale (NIHSS) scores, modified Rankin Score (mRS) and Glasgow Coma Scale scores were recorded. Etiological classification of stroke was done. These parameters were compared in terms of age groups, genders, and hemorrhagic complications. Significant differences were found between age groups concerning hypertension, coronary artery disease, smoking status, and antiaggregant use. Rate of hemorrhagic complications in rtPA group was significantly lower when compared with other treatment groups. Hemorrhagic complications developed mostly in the rtPA+thrombectomy group. Among the patients who developed hemorrhagic complications, NIHSS scores on admission were found to be significantly lower in men than women. Admission, discharge, and 3rd month mRS values in men were significantly lower than those of women. Knowing demographic and clinical features of patients that may have an impact on the clinical course of ischemic stroke managed with reperfusion therapy will be useful in predicting the hemorrhagic complications and clinical outcomes.

The value of thrombolysis for the management of acute ischemic stroke: a cost effectiveness analysis based on real world data from the SUN4P study

Background: Previous studies have shown that patients with Acute Ischemic Stroke (AIS) treated with recombinant tissue plasminogen activator (rtPA) have better clinical and in several cases economic outcomes than those who are not. However, the cost-effectiveness of rtPA in the Greek setting is totally unknown. This study aims to evaluate the cost-effectiveness of rtPA for the management of AIS in Greece based on real world data (RWD). Methods: A cost-effectiveness model was developed in Microsoft® Excel to examine the clinical and economic impact of rtPA from a Greek third-party payer perspective based on RWD collected during the “Improving Stroke Care in Greece in Terms of Management, Costs and Health Outcomes” project, with the participation of nine Greek hospitals from different cities. The primary outcome of the analysis was the incremental cost-effectiveness ratio (ICER) expressed in euros per quality adjusted life year (QALY). The primary clinical outcome was the mRS value at 3 months. Robustness of the results was tested using both one-way and probabilistic sensitivity analyses. Results: Compared with conservative management, rtPA led to 0.009 incremental QALYs per patient in the first 3 months. The total cost per patient incurred by the rtPA group was 2,196.65€, compared to 2,499.45€ in the conservative treatment group, leading to 302.79€ savings per patient, indicating that rtPA is more effective and costs less than conservative management from a Greek third-party payer perspective. However, probabilistic sensitivity analyses (PSA) showed that there is a significant variability and the probability of rtPA to be cost effective or dominant in the Greek setting is between 58.9%-74.1% within the threshold of one to three times the national GDP per capita. Conclusion: Intravenous rtPA represents a dominant or cost-effective strategy for the management of AIS in Greece. The analysis may have underestimated the potential benefits of rtPA. Although this study provides additional evidence to decision-makers, more data are required to improve the robustness of the conclusion

Mediation of long-pulsed ultrasound enhanced microbubble recombinant tissue plasminogen activator thrombolysis in a rat model of platelet-rich thrombus.

Ultrasound (US)-enhanced microbubble (MB) therapy has been investigated as a therapeutic technique to facilitate the thrombolysis for the treatment of pericardial and microvascular obstruction. This study sought to assess the therapeutic effects of long-pulsed US-assisted MB-mediated recombinant tissue plasminogen activator (rt-PA) thrombolysis in a rat model of platelet-rich thrombus. Ferric chloride (10%) was used to induce total arterial occlusion before formation of platelet-rich thrombi. Therapeutic long-tone-burst US (1 MHz, 0.6 MPa, 1,000-µs pulse length) was used, and 2.9×109/mL of lipid MBs and 1 mg/mL of rt-PA were infused. Subsequently, 42 Sprague-Dawley (SD) male rats were randomly divided into seven groups: (I) control; (II) rt-PA; (III) high duty cycle US + MB; (IV) low duty cycle US + rt-PA; (V) high duty cycle US + rt-PA; (VI) low duty cycle US + rt-PA + MB; and (VII) high duty cycle US + rt-PA + MB. The recanalization grades were evaluated after 20 minutes' treatment. Compared to the control, there was significant improvement in recanalization in the US + rt-PA groups (P=0.01 vs. control), US (low duty cycle) + rt-PA + MB (P=0.003 vs. control) and US (high duty cycle) + rt-PA + MB (P<0.001 vs. control) groups, in which recanalization was successfully achieved in all rats. Long-pulsed US-enhanced MB-mediated rt-PA thrombolysis offered a powerful approach in the treatment of platelet-rich thrombus.

Optional therapeutic management of intermediate-risk pulmonary embolism patients

Background: Few studies have evaluated the thrombolytic treatment in patients with intermediate-high risk pulmonary embolism, making this study more valuable. Material and methods: It was a prospective, non-randomized, open-label, single-center study. Eligible patients at the age of 18 or older with an acute pulmonary embolism (PE) confirmed by CT pulmonary angiography with onset until 14 day and signs of right ventricular (RV) overload on echocardiography took part in the study. Pulmonary Arterial CT Obstruction Index Rate (PACTOIR) was used to define the localization and the expansion zone of thromboembolism. This study included 18 patients with intermediate risk and acute submassive pulmonary thromboembolism. In thrombolysis (TT) group (n=9) were used 50 mg of tissue-plasminogen activator (t-PA) administered in infusion as 0.4 mg/h for 2 hours. In the standard anticoagulation group, unfractioned heparin (UFH) was administered as a bolus of 70 units/kg or a maximum of 5000 units, followed by continuous infusion at an initial rate of 16 units/kg or a maximum of 1000 units/h. Results: The mean age for TT group was 69 vs 63 for the UFH group. PACTOIR was 100% in 3 patients in the half-dose rt-PA group and in 2 patients in the UFH group. RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p &lt; 0.0001). Mean pulmonary artery systolic pressure was 55 mm Hg in both groups (p &lt; 0.05), with 53 [43–60] in TT group vs. 41.5 [37–45] mmHg in UFH group, P&lt;0.05. Also, RV/ LV ratio and systolic PAP decreased significantly in both groups. Severe bleeding with a need in red blood cell transfusion was seen in 0.11% (1 patient) in the TT group vs 0 in UFH group. The hospitalization length of stay was significantly shorter in the TT group (3.8±1.8, p &lt; 0.05). The rate of secondary endpoints was significantly higher in the UFH group with a high rate of pulmonary hypertension (0 vs. 19%, p=0.003). Conclusions: Half-dose thrombolytic therapy in patients diagnosed with submassive pulmonary embolism significantly reduced death and hemodynamic decompensation in the first 7 days compared to anticoagulant therapy only. With all that being said, it can be concluded that patients with high-intermediate risk PE could benefit from reduced-dose TT.

EFFICACY AND SAFETY OF INTRAVENOUS THROMBOLYTIC THERAPY IN PATIENTS OVER EIGHTY YEARS

: Introduction: Intravenous thrombolytic therapy (IVTT) is licensed for patients under 80 years in many countries. In this study, we aimed to demonstrate functional results and complication rates of IVTT in patients over eighty years and whether there is a difference in efficacy and safety between low dose and standard dose recombinant tissue plasminogen activator (rTPA). Methods: A retrospective observational study of patients over eighty who admitted to Suleyman Demirel University Faculty of Medicine Hospital between August 2016 and April 2021 and to Isparta City Hospital between April 2017 and April 2021 and diagnosed with acute ischemic stroke were conducted. Third month modified rankin scores (mRS) and mortality rates of patients and hemorrhagic transformations were determined. Results: There were 29 patients in IVTT group and 25 patients in non-IVTT group. By the third month, it was observed that functional independence (mRS 0-2) ratio was increased more in IVTT group, but it wasn’t statistically significant (p: 0.087). In mortality and symptomatic intracerebral hemorrhage rates, there wasn't statistically significant diffirence between IVTT and non-IVTT groups and low dose and standard dose rTPA groups by the third month. Conclusion: The efficacy and complication rates of IVTT in patients over 80 years were found similar to not receive IVTT. These results support the safety of IVTT in patients over 80 years. In low or standard dose rTPA preference, we observed that there wasnt’ statistically significance in efficacy and safety. We believe that these results will be supported by studies with larger number of patients.

Biosimilar Tenecteplase Versus Alteplase in Acute Ischemic Stroke: A Real World Study.

There is an unmet need for a more effective thrombolytic agent in acute ischemic stroke (AIS) management. Various studies and meta-analysis suggest tenecteplase (TNK) as non-inferior over alteplase (rTPA). The present single-center study compares biosimilar TNK and rTPA in a tertiary care setting. Data of patients who presented with AIS and underwent intravenous thrombolysis (IVT) were recruited retrospectively from January 2018 to July 2021. Primary efficacy outcome was a modified Rankin score (mRS) at 90 days dichotomized at < = 2. Qualitative and quantitative variables were assessed using Chi-square test and Student's t-test, respectively. A total of 160 patients, 103 in the rTPA and 57 in TNK group, were analyzed. The baseline characteristics were well matched apart from hypertension. Large artery atherosclerosis was the most frequent subtype of stroke among the two groups. Good functional outcome was seen in 47.92% of patients TNK and 64.77% of patients in rTPA group (p = 0.069). No difference was seen in the rates of any ICH (p = 0.29) and mortality at 3 months (p = 0.32) among the two groups. This present study observed no difference in the efficacy and safety between biosimilar TNK and rTPA. Our findings are in concordance with published trials showing equivalence between the two molecules.

Can chronic kidney disease staging early predict outcome of large-artery ischemic stroke with impaired renal function?

Ischemic stroke poses a major threat to human beings, and a prompt intravenous thrombolytic management remains the gold standard protocol for stroke sufferers. Although the role of thrombolytic therapy (r-tPA) for ischemic stroke patients and those with underlying impaired renal function has been advocated as effective treating strategy, there is still a lack of investigation as to finding out baseline important variables that are capable of early outcome prediction. In this project, we hypothesize that the change of clinical chronic kidney disease (CKD) staging (delta stage = CKD stage after 3-month follow-up - CKD stage at admission) could serve as a crucial predictor of the prognosis of patients. This is a cohort longitudinal retrospective study. A total of 765 cerebral artery ischemic stroke patients with impaired renal function were recruited and followed up for 1 year. Among them, 116 had received the thrombolytic treatment (r-tPA) after being evaluated at the triage in the emergency department and the rest had not (non-r-tPA). Propensity-matching was applied to compare the mortality between the r-tPA and non-r-tPA groups. Multiple logistic regression (LR) and decision tree (DT) algorithm were used to identify important prediction factors for mortality as well as the improvement in neurological function. The 1-year mortality rates for r-tPA and non-r-tPA groups were 32.8% and 44.4%, respectively. The propensity-matched odds ratio of mortality for the r-tPA group compared with the non-r-tPA group is 0.469, with p = 0.003. Logistic regressions suggest that age, Hct, diabetes mellitus type 2, coronary artery disease, and delta stage are important factors for mortality for the non-r-tPA group, whereas age, diabetes mellitus type 2, chronic heart failure, hospital day, and delta stage are important factors for the r-tPA group. On the usage of antihypertensive drugs, ACEI/ARB was not associated with mortality (p = 0.198), whereas the diuretic was, with odds ratio at 1.619 (p = 0.025), indicating higher mortality after administration. Both LR and DT analyses indicate that delta stage is the most important predictor. For the r-tPA group, patients with delta stage ⩽0 had a 24% mortality, while that for delta stage >0 the mortality is 75%. For non-r-tPA patients, the corresponding mortalities were 30.9 and 66.3, respectively. Delta stage is also useful for predicting patients' improvement of neurological function, assessed by NIHSS, mRS, and Barthel Index. The areas under the curve for the three assessments are 0.83, 0.835, and 0.663, respectively. Large-artery ischemic stroke patients who received thrombolytic treatment had significantly lower mortality, even when presenting underlying impaired renal function. The change of CKD staging (delta stage) is capable of acting as a powerful clinical baseline surrogate for both r-tPA and non-r-tPA patients in terms of early outcome prediction. Long-term use of diuretics could be potentially harmful to this group of patients. Moreover, delta stage correlates well with clinical long-term neurological functionality assessment (NIHSS, mRS, and Barthel index), which is helpful in aiding urgent clinical decision-making.

Sono-assisted-thrombolysis by three-dimensional diagnostic ultrasound improves epicardial recanalization and microvascular perfusion in acute myocardial infarction.

BackgroundThis study aimed to evaluate the multiple interactions between therapeutic ultrasound (TUS), microbubbles (MB), and recombinant tissue plasminogen activator (r-tPA) by using three-dimensional (3D) ultrasound to examine the impact of thrombolysis with r-tPA on epicardial recanalization and microcirculation in patients with acute ST-segment-elevation myocardial infarction (STEMI).MethodsAcute thrombotic occlusion of the left anterior descending (LAD) artery was induced in 32 Bama pigs, who were fed a high-cholesterol diet and randomized into four groups: (I) a 3D-sono-assisted-thrombolysis (3D/TUS + MB + r-tPA) group; (II) a 3D/TUS + MB group; (III) a full-dose r-tPA group; and (IV) a 3D/TUS alone group. Epicardial angiographic recanalization rate, microcirculation in the at-risk myocardium, ST-segment elevation on electrocardiogram, and changes in the at-risk myocardium and the myocardial infarct area were compared between the groups.ResultsAfter treatment, distal LAD recanalization was observed in 87.5% (7/8) of pigs in the 3D/TUS + MB + r-tPA group, which was significantly higher than the rates observed in the 3D/TUS + MB (37.5%) and the full-dose r-tPA (50.0%) groups (all P<0.05). The average acoustic intensity in the 3D/TUS + MB + r-tPA group (193.78±10.15 dB) was also significantly higher than that in the 3D/TUS + MB (154.29±31.94 dB) and the r-tPA (141.42±28.31 dB) groups (all P<0.05). The decrease in ST-segment elevation in the 3D/TUS + MB + r-tPA group (1.31±1.22 mm) was significantly higher than that in the 3D/TUS + MB (5.38±1.77 mm) and the r-tPA (4.30±2.08 mm) groups (all P<0.05). Furthermore, the ratio of the infarcted myocardial area divided by the at-risk myocardial area was markedly lower in the 3D/TUS + MB + r-tPA group (0.51±0.14) than in the 3D/TUS + MB (0.69±0.28) and r-tPA (0.75±0.23) groups (all P<0.05).ConclusionsThree-dimensional sono-assisted-thrombolysis directly improves infarct-related recanalization rates, enhances microcirculation, reduces r-tPA dosage, and ameliorates the thrombolytic effect of r-tPA in acute STEMI.

Elevated NT-proBNP levels are associated with CTP ischemic volume and 90-day functional outcomes in acute ischemic stroke: a retrospective cohort study

ObjectiveTo investigate the impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on CTP infarct core volume and poor 90-day functional outcomes in acute ischemic stroke (AIS).MethodsA total of 403 hospitalized patients with AIS in the Stroke Center of the First Hospital Affiliated to Soochow University were enrolled from March 2018 to January 2021. The association between NT-proBNP and clinical outcomes in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Also, subgroup analyses were conducted based on treatment decisions.ResultsNT-proBNP was positively correlated with CTP ischemic volume (p < 0.001), infarct core volume (p < 0.001), and ischemic penumbra volume (p < 0.001). Univariate analysis showed that the influence of NT-proBNP and functional outcomes were statistically significant in model 1 (p = 0.002). This phenomenon was persistent after adjusted for age, sex, and body mass index in model 2 (p = 0.011), adjusted for SBP, current smoking, family history of stroke, hypertension, and diabetes mellitus in model 3 (p < 0.001), and adjusted for TnI, D-dimer, PLT, Cr, TC, TG, HDL-C, treatment decisions, and NIHSS score in model 4 (p = 0.027). A high NT-proBNP was associated with a high 90-days mRS score among the total population, IV rt-PA, and standardized treatment groups, but not in IV rt-PA + EVT, EVT, and EVT/IV rt-PA + EVT groups.ConclusionElevated NT-proBNP levels reveal large CTP infarct core volume and poor 90-day functional outcome in AIS. NT-pro BNP is an independent risk factor for functional outcomes.

Safety and efficacy of low-dose rt-PA with tirofiban to treat acute non-cardiogenic stroke: a single-center randomized controlled study

Background and purposeThe recanalization rate after intravenous thrombolysis (IVT) is not enough and there is still the possibility of re-occlusion. We aim to investigate the effectiveness and safety of infusing tirofiban after IVT.MethodsWe performed a prospective controlled study of 60 patients with acute non-cardiogenic ischemic stroke who were hospitalized in Yantai Yuhuangding Hospital from January 2018 to December 2019. The patients were divided into 2 groups: those who received tirofiban for 24 h after IVT (rt-PA + T group) and those who did not receive postprocedural intravenous tirofiban (rt-PA group). The rt-PA + T group received low-dose rt-PA (0.6 mg/kg). The rt-PA group received standard dose rt-PA (0.9 mg/kg). The main outcome measure were safety, included the symptomatic intracranial hemorrhage (sICH), any ICH, severe systemic bleeding, and mortality. The secondary outcome measure is curative efficacy which were evaluated by the 7d-NIHSS score and functional outcomes at 90 days. During hospitalization, the deterioration of neurological function was recorded.ResultsAll patients completed the follow-up with complete data, there were 30 patients in each of groups. The general characteristics between the two group patients had no statistically significant differences. Compared with the rt-PA + T group and the rt-PA group, in terms of safety, the rates of the sICH, severe systemic bleeding, and mortality in both groups were 0, and there was no statistically significant difference in the rates of any ICH between the two groups (10.0% vs. 3.3%, P = 0.306). In terms of efficacy, the rate of the early neurological deterioration events (END) was no statistical significance (0 vs. 6.6%, P = 0.246). There was no significant difference in the NIHSS score between the two groups before the IVT, and also at 24 h, however, the 7d-NIHSS score was lower in the rt-PA + T group compared with the rt-PA group (2.33 ± 1.85 vs. 4.80 ± 4.02, P = 0.004). At 90 days, 83.3% of patients in the rt-PA + T group had favorable functional outcomes compared with 60.0% of patients in the rt-PA group (P = 0.045).ConclusionsLow-dose rt-PA combined with tirofiban in acute non-cardiogenic ischemic stroke did not increase the risk of ICH, and mortality, and it was associated with neurological improvement.Trial RegistrationThe trial has been registered at the ChiCTR and identified as ChiCTR1800014666 (28/01/2018).

Effect of microbubbles on transcranial doppler ultrasound-assisted intracranial recombinant tissue-type plasminogen activator thrombolysis.

The aim of this study was to evaluate the effect of microbubbles on the efficacy of transcranial doppler (TCD) ultrasound-assisted thrombolytic therapy of recombinant tissue-type plasminogen activator (rt-PA). Male New Zealand white rabbits (n = 36) were randomly divided into an rt-PA group (n = 18) and an rt-PA plus microbubble group (n = 18). After the cerebral infarction model was constructed with autologous blood clots, rt-PA and rt-PA plus microbubble intervention were performed, respectively. The hemodynamic changes and infarct size of the two groups were recorded. In addition, the ELISA method was used to detect the level of nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) in the brain tissue of the two-group graph model and high-sensitivity C-reactive protein (hs-CRP) in the serum. In the rt-PA group, the recanalization rate was 38.9% and the average infarct size was 11.8%. In the rt-PA plus microbubble group, the recanalization rate was 66.7% and the average infarct size was 8.2%. In addition, the average values for NO, SOD, MDA, and hs-CRP were 16.48 ± 5.39 μmol/L, 730.2 ± 9.86 U/mg, 0.92 ± 0.43nmol/mg, and 8.56 ± 1.64mg/L in the rt-PA group, respectively, and the average values were 9.18 ± 3.37 μmol/L, 426.2 ± 6.39 U/mg, 0.73 ± 0.44nmol/mg, and 5.23 ± 0.94mg/L in the rt-PA plus microbubble group, respectively. The addition of microbubbles enhanced the effects of TCD-assisted rrt-PA thrombolysis.

Intravenous Alteplase Treatment of Acute Ischemic Stroke Patients Exhibiting Mild Neurological Deficits.

Alteplase is increasingly used for treating ischemic stroke cases with low NIHSS scores, but the guidelines and evidence regarding outcomes are lacking. So, the authors conducted an updated meta-analysis to better understand the effects of alteplase for the treatment of acute mild ischemic stroke. PubMed, Cochrane, EMBASE were systematically explored for all relevant investigations published as in September 2021. Study quality was assessed as per the Cochrane system criteria, and Stata 15.1 was utilised to carry out a meta-analysis. In total, 16 trials incorporating 5,846 patients were analysed (1,926 and 3,920 cases in the rt-PA and non-thrombolytic groups, respectively). The main outcome measure revealed that the treatment of rt-PA was correlated with better odds of a modified Rankin Scale (mRS) score of 0-1 relating to the non-thrombolytic group (OR = 1.12, 95% CI = 1.02-1.23, p <0.05), and with moderate heterogeneity (I2 = 0.0%, p = 0.930). For the secondary study outcomes, symptomatic intracranial hemorrhage incidence was 4.46 times greater in the group of rt-PA, relating to the non-thrombolytic group (OR = 4.46, 95% CI = 2.75-7.23, p <0.001). There were no considerable differences in the mortality between the two groups (OR = 0.64, 95% CI = 0.39-1.03, p >0.05). No significant heterogeneity was detected in secondary study outcomes. Subgroup analysis showed that the function outcomes was the best within 3-4.5 hours; and the risk and mortality of sICH were the lowest within 3-4.5 hours. Intravenous rt-PA administration is associated with improved functional outcomes at three months after the stroke in mild ischemic stroke patients. Key Words: Acute ischemic stroke, Mild, Alteplase, Meta-analysis.

Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study

BackgroundTenecteplase (TNK) possesses several pharmacological characteristics superior to conventional alteplase (rt-PA), with well-established safety and efficacy profile in Caucasians. There exists controversy over the optimal dose of intravenous rt-PA for...

Comparison of side effects between thrombolytic and anticoagulation therapy in patients with pulmonary embolism

Purpose: The treatment of Pulmonary Embolism (PE) which is a life-threatening disease must be planned considering the risk-benefit relationship. In this study, patients with PE given thrombolytic therapy, low-molecular-weight heparin, and warfarin were monitored for 5 years to compare them in terms of hemorrhage side effects due to therapy. Method: A total of 219 patients were included in the study. 50.2% (n=109) of the patient’s were female and 49.8% (n=110) were male, (p=0.20). Clinical findings, radiologic and laboratory parameters, treatments and side effects were recorded. A total of 121 (55.25%) patients were given thrombolytic therapy (Group 1 n=121). Enoxaparin therapy was given to 205 patients (Group 2). During therapy maintenance, warfarin therapy was conducted for 159 patients (Group 3). Results: Cerebral hemorrhage observed in 1 case (0.83%) in group 1, 2 case (0.98%) in group 2 and 1 cases (0.62%) in group 3 (p&gt;0.05). Gastrointestinal system (GI) bleeding happened 2 cases (1.65%) in group 1 and 2 cases (0.98%) in group 2 (p&gt;0.05). Minor bleeding was observed at similar rates due to the treatments. There was no fatality due to hemorrhage. There is no significant difference in terms of death, recurrence, residual chronic thrombus, and chronic PE in the follow-up for five years between the rt-PA group (group1) and non-rt-PA group (p&gt;0.05). Conclusion: According to our results; major hemorrhage was observed similarly in thrombolytic, enoxaparin, and warfarin therapy. Study results about the rate of cerebral hemorrhage related to thrombolytic therapy were low in contrast to the results reported in the literature before.

Low-dose thrombolysis for submassive pulmonary embolism

The role of thrombolysis in submassive pulmonary embolism (PE) is controversial due to the high risk of hemorrhage. This study aimed to evaluate the role of half-dose tissue-type plasminogen activator...

Intra-Arterial Thrombolysis after Unsuccessful Mechanical Thrombectomy in the STRATIS Registry.

Recent data suggest that intra-arterial thrombolytics may be a safe rescue therapy for patients with acute ischemic stroke after unsuccessful mechanical thrombectomy; however, safety and efficacy remain unclear. Here, we evaluate the use of intra-arterial rtPA as a rescue therapy in the Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) registry. STRATIS was a prospective, multicenter, observational study of patients with acute ischemic stroke with large-vessel occlusions treated with the Solitaire stent retriever as the first-line therapy within 8 hours from symptom onset. Clinical and angiographic outcomes were compared in patients having rescue therapy treated with and without intra-arterial rtPA. Unsuccessful mechanical thrombectomy was defined as any use of rescue therapy. A total of 212/984 (21.5%) patients received rescue therapy, of which 83 (39.2%) and 129 (60.8%) were in the no intra-arterial rtPA and intra-arterial rtPA groups, respectively. Most occlusions were M1, with 43.4% in the no intra-arterial rtPA group and 55.0% in the intra-arterial rtPA group (P = .12). The median intra-arterial rtPA dose was 4 mg (interquartile range = 2-12 mg). A trend toward higher rates of substantial reperfusion (modified TICI ≥ 2b) (84.7% versus 73.0%, P = .08), good functional outcome (59.2% versus 46.6%, P = .10), and lower rates of mortality (13.3% versus 23.3%, P = .08) was seen in the intra-arterial rtPA cohort. Rates of symptomatic intracranial hemorrhage did not differ (0% versus 1.6%, P = .54). Use of intra-arterial rtPA as a rescue therapy after unsuccessful mechanical thrombectomy was not associated with an increased risk of symptomatic intracranial hemorrhage or mortality. Randomized clinical trials are needed to understand the safety and efficacy of intra-arterial thrombolysis as a rescue therapy after mechanical thrombectomy.

Short-term outcome in ischemic stroke patients after thrombolytic therapy

BackgroundStroke represents the second leading cause of death in the world after myocardial infarction. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (alteplase, rt-PA) is the only pharmacological therapy that was approved for treatment within 4.5 h of acute ischemic stroke (AIS) onset. We aimed to predict the 3-month outcome of AIS patients who received alteplase regarding mortality, spontaneous intra-cerebral hemorrhage (sICH), and functional outcome in comparison with non-thrombolyzed patients and to evaluate the predictors of the outcome after 3 months.MethodsAll the clinical, National Institute of Health Stroke Scale (NIHSS) scores, radiological, and laboratory data of 40 AIS patients and received rt-PA during the period from 2016 to 2018 were collected and analyzed retrospectively. For comparison, 40 patients, as a control group, were selected to match the alteplase group as regards the baseline data and received regular treatment, rather than rt-PA within the first 24 h, that were obtained. The outcome of the thrombolyzed patients after 3 months was evaluated in comparison with controls by using a modified ranking scale.ResultsAfter a 90-day follow-up period, the death rate was slightly higher among the rt-PA group (7.5%) in comparison with the control group (5%). sICH occurred in 7.5% of the patients in the alteplase group and in 5% of the non-thrombolyzed patients; however, this difference was not significant. More patients had a favorable outcome (mRS = 0–2) in the rt-PA group than in the control group (65% vs 60%, OR 1.38, 95% CI 0.50–3.6, P = 0.51). NIHSS score on admission, body mass index (BMI) (≥ 30), and previous transient ischemic attacks (TIA)/previous ischemic stroke were significant predictors of outcome after IV thrombolysis. Age, sex, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, smoking, atrial fibrillation (AF), stroke subtype, size of infarction, and hyperdense middle cerebral artery had a non-significant effect.ConclusionAfter 3 months of follow-up, rt-PA had a non-significant more increase of favorable outcome with increased risk of sICH and death than controls. Baseline NIHSS, BMI, and history of TIA or previous ischemic stroke were significant predictors of outcome after thrombolysis.

Assessing the Clinical Efficacy of Recombinant Tissue Plasminogen Activator on Acute Cerebral Infarction.

To assess the efficacy of intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis on clinical outcomes and risk of death in patients with acute cerebral infarction. Patients (n = 258) with acute cerebral infarction, treated within 4-5 h of the episode, were grouped according to whether intravenous thrombolysis was performed using rt-PA or not. Both groups received routine treatment for cerebral infarction, but the former received rt-PA intravenously at a dosage of 0.9 mg/kg. The National Institutes of Health Stroke Scale (NIHSS) score, clinical efficacy, and risk of bleeding and death were compared between the two groups. The NIHSS score and clinical effects for the rt-PA group were more favorable than those of its counterpart (P < 0.05), though there was no significant difference in risk of an intracranial hemorrhage. The mortality rate for the rt-PA group was lower than that of the control group (P < 0.05). Administration of intravenous rt-PA thrombolysis within 4.5 h of an acute cerebral infarction had a significant impact and did not increase risk of intracranial hemorrhage or death.