Tenecteplase versus alteplase for acute ischemic stroke thrombolysis: a systematic review and meta-analysis

Background: Intravenous thrombolysis is the preferred clinical treatment for acute ischemic stroke. Alteplase is an intravenous thrombolytic drug used in clinical practice. Recently, studies have shown the efficacy of another intravenous thrombolytic drug, tenecteplase, and have reported that the risk of bleeding is low. However, at present, Chinese and international research has yielded controversial results regarding the efficacy and risks of tenecteplase. Therefore, this systematic review and meta- analysis of the efficacy and safety of tenecteplase were performed. Methods: PubMed, the Cochrane Library, MEDLINE, the Wanfang Database and CNKI were searched for all studies on the thrombolytic treatment of acute ischemic stroke. All studies published in English prior to March 2021 were retrieved. The studies were screened and selected based on the inclusion and exclusion criteria. Then, the data were extracted and recorded by trained researchers. RevMan 5.4 statistical software was used to analyze the data on the 24h recanalization rate, early neurological improvement (24h reduction in the National Institutes of Health Stroke Scale [NIHSS] score of at least 8 points or 24 h NIHSS score of 0~1 point), mRS score at 90 days, intracranial hemorrhage, symptomatic intracranial hemorrhage and mortality in the tenecteplase group and alteplase group. Results: A total of 565 related studies were identified through the initial searches in each database. The citations of meta-analyses and related reviews were screened for additional eligible articles. Eventually, 9 high-quality English-language articles that included 2149 patients with acute ischemic stroke (including 1035 in the tenecteplase group and 1046 in the alteplase group)were included in this meta-analysis. The meta-analysis results were as follows: (1) Efficacy: The 24 h recanalization rate with regard to vascular recanalization was significantly better in the tenecteplase group than in the alteplase group(OR = 1.83, 95% CI: 1.23~2.72, z = 2.97, P = 0.003). There was significantly greater improvement in early neurological function in the tenecteplase group than in the alteplase group (OR= 1.34, 95% CI: 1.11~1.63, Z=3.00, P =0.003). There were no significant differences in 90-day mRS scores between the two groups (mRS score =0-1, OR = 1.20, 95% CI: 0.99~1.46, z = 1.82, p = 0.07; mRS score =0-2, OR = 1.17, 95% CI: 0.94~1.45, z = 1.38, p = 0.17). However, the subgroup analysis showed that the 90-day mRS score of the 0.25 mg/kg tenecteplase group was significantly different from that of groups treated with other doses of tenecteplase (OR = 1.48, 95% CI: 1.01~2.03, z = 2.03, p = 0.04). (2) Safety: The incidences of any intracranial hemorrhage (OR = 0.91, 95% Ci: 0.55~1.49, z = 0.39, p = 0.70), symptomatic intracranial hemorrhage (OR = 1.21, 95% CI: 0.63~2.32, z = 0.56 P = 0.57), and mortality (OR = 0.85, 95% CI: 0.57~1.26, z = 0.82, p = 0.41) were not significantly different between the tenecteplase and alteplase groups. Conclusions: Tenecteplase can significantly increase the 24-hour vascular recanalization rate and improve the neurological prognosis of patients with acute ischemic stroke and it does not increase the risk of intracranial hemorrhage or mortality.

Preparation and Properties of Thrombus-Targeted Urokinase/Multi-Walled Carbon Nanotubes (MWCNTs)-Chitosan (CS)-RGD Drug Delivery System

In order to improve the therapeutic effect, prolong the action time and reduce the side effects of the first generation thrombolytic drug urokinase (UK), a novel UK/multi-walled carbon nanotubes (MWCNTs)-chitosan (CS)-arginine-glycine-aspartic acid (Arg-Gly-Asp) (RGD) drug delivery system was synthesized by chemical bonding/non covalent bond modification/ultrasonic dispersion. The results showed that the diameter of the UK/MWCNTs-CS-RGD drug delivery system was about 30–40 nm, there was a layer of UK was attached to the surface of the tube wall, and the distribution was relatively uniform. The average encapsulation efficiency was 83.10%, and the average drug loading was 12.81%. Interestingly, it also had a certain sustained-release effect, and its release law was best fitted by first-order kinetic equation. Moreover, the accelerated and long-term stability test results show that it had good stability. Compared with free UK, UK/MWCNTs-CS-RGD had thrombolytic effect in vitro. In addition, MTT experiment showed that the prepared MWCNTs-CS-RGD nanomaterials had good biocompatibility. A rabbit model of carotid artery thrombosis was used to conduct targeted thrombolysis experiments in vivo. Compared with free UK, UK/MWCNTs-CS-RGD could be enriched in the thrombosis site to achieve thrombus targeting. UK/MWCNTs-CS-RGD drug delivery system was expected to become an effective thrombolytic drug for targeted therapy of thrombosis.

Study on the therapeutic and nursing effect of thrombus targeted thrombolysis mediated by recombinant plasminogen activator modified nanoparticles on stroke patients

Tissue plasminogen activator (rt-PA) is a thrombolytic drug used for the treatment of stroke. However, it has a short half-life and a high risk of complications of cerebral hemorrhage, which complicates its use in clinical applications. In this study, polyethylene glycol and polycaprolactone were used as nano-carriers in the development of new nano-drug-recombinant plasminogen activator modified nanoparticles (PEG-PCL@rt-PA) loaded with rt-PA. Following treatment, the patients received with either conventional nursing or continuous nursing. Compared with traditional treatment and nursing, the nanoparticles had stronger thrombolytic and therapeutic effects, significantly improved the self-care recovery rate of patients, and reduced the occurrence of complications. This new mode of PEG-PCL@rt-PA drug therapy combined with continuous nursing is expected to improve the recovery and survival rates of stroke patients.

Efficacy of thrombolytics in patients with acute coronary syndrome

Funding Acknowledgements Type of funding sources: None. Background/Introduction: The optimal choice of the thrombolytic drug for emergency revascularization in patients with acute coronary syndrome (ACS) still remains to be defined. Percutaneous coronary intervention is a more safe and effective method of reperfusion compared with thrombolytic therapy, that’s why the last is relatively not common nowadays. But in the COVID-19 era in a number of cases some patients with ACS can’t be quickly hospitalized due to different reasons like the absence of the nearest available cardiovascular center, or lack of an ambulance. A long period of chest pain forces the doctors to use systemic thrombolytic therapy. Purpose This study investigates the efficacy and safety of Alteplase, Prourokinase, Tenecteplase, and Streptokinase in patients with acute coronary syndrome. Methods A retrospective, open, non-randomized cohort study was conducted. We have analysed 600 patients with ACS, who underwent systemic thrombolytic therapy at the prehospital and in-hospital stages from 2009 to 2011. Patients were divided into several groups according to the thrombolytic agent administered: Alteplase (254 patients), Prourokinase (309 patients), Tenecteplase (6 patients), Streptokinase (31 patients). Treatments were to be given as soon as possible. The ECG reperfusion criterion was a decrease in the ST segment by 50% or more from the initial elevation. Results Among 600 patients (mean age, 61 years (SD = 20); 119 women [19.7%]), 440 had successful reperfusion. The median time from chest pain onset to the start of treatment was 3 hours (P < 0.001). The percentages of successful thrombolysis for each agent were similar: Alteplase 74,4% Prourokinase 71,2%, Tenecteplase 83%, Streptokinase 74,2%. No statistical differences were observed in thrombolytic results among these groups (OR: 0.60, 95% CI: 0,2868 to 1,217; P = 0.17). At the same time, the hospital treatment with prourokinase was more effective than prehospital care with prourokinase: 110 successful reperfusions in 138 patients (79.7%) and 110 successful reperfusions in 171 patients (64.3%), respectively. Regardless of the onset of the attack (OR: 0.45, 95% CI: 0,2004 to 0,9913; P = 0.05). The effectiveness of the other thrombolytics cannot be compared between prehospital care and hospital treatment due to the rare use at the hospital stage in our cases. In the study, there was also no statistical difference in complication rates among the treatment groups. Among all patients, there were 9 fatal outcomes (1.5%): Alteplase 3,15% Prourokinase 1,9%, Streptokinase 3,22%. Conclusion(s): In patients with ACS, all thrombolytic drugs showed similar effectiveness. There is no difference in the safety and efficacy among the agents in our study, but there is a difference in cost and route of administration. However, upcoming prospective trials with long follow-up periods might be expected to determine the most appropriate systemic thrombolytic drug.

Reperfusion failure despite recanalization in stroke: New translational evidence

Current treatment for acute ischemic stroke aims at recanalizing the occluded blood vessel to reperfuse ischemic brain tissue. Clot removal can be achieved pharmacologically with a thrombolytic drug, such as recombinant tissue plasminogen activator, or with mechanical thrombectomy. However, reopening the occluded vessel does not guarantee full tissue reperfusion, which has been referred to as reperfusion failure. When it occurs, reperfusion failure significantly attenuates the beneficial effect of recanalization therapy and severely affects functional recovery of stroke patients. The mechanisms of reperfusion failure are somewhat complex and not fully understood. Briefly, after stroke, capillaries show stalls, constriction and luminal narrowing, being crowded with neutrophils, and fibrin–platelet deposits. Furthermore, after recanalization in stroke patients, a primary clot can break, dislodge, and occlude distal arterial branches further downstream. In this review, we highlight a rodent model that allows studying the pathophysiological mechanisms underlying reperfusion failure after stroke. We also describe the vascular and intravascular changes involved in reperfusion, which may provide relevant therapeutic targets for improving treatment of stroke patients.

Long-term echocardiography results in patients with ST-segment elevation myocardial infarction after pharmaco-invasive reperfusion therapy, depending on the choice of thrombolytic drug

Objectives: to analyze the results of echocardiography 1 year after STEMI in patients undergoing pharmaco-invasive reperfusion using various thrombolytic drugs.Materials and Methods: 240 patients with STEMI after pharmaco-invasive reperfusion were included in an open-label prospective cohort study. Depending on the thrombolytic agent used, the patients were divided into 4 groups: in the 1st (n = 73) — lysis was performed with alteplase; in the 2nd (n = 40) — tenecteplase; in the 3rd (n = 95) — forteplase; in the 4th (n = 32) — streptokinase. Depending on the fibrin-specificity of the thrombolytic, all patients were presented with 2 groups: the group of fibrin-specific thrombolytics (FST, n = 208) and the group of fibrin-nonspecific streptokinase (FNST, n = 32). Echocardiography was assessed 1 year after reperfusion.Results: after 1 year, there was a slight violation of the global LV systolic function, while the EF between the groups did not differ (p = 0.420). A higher EF was recorded in the FST group compared with FNST (49.8 ± 7.4 % versus 47.4 ± 6.8 %; p = 0.048). After 1 year, violations and local LV contractility persisted in each of the four groups (p = 0.161). At the same time, lower WMSI were recorded in the FST group compared to FNST (1.19 [1.06; 1.38] versus 1.25 [1.175; 1.5]; p = 0.029). In the FST group, significantly lower iEDV were recorded (p = 0.048), and iESV (p = 0.022) and LA size (p = 0.007) compared with FNST. In dynamics, 1 year after reperfusion in the FST group, there was a significant increase in EF by 5.5 % (p = 0.000) and a decrease in LV WMSI by 5 % (p = 0.000) compared with the FNST group.Conclusions: pharmaco-invasive treatment of STEMI with the use of thrombolytic drugs after 1 year of follow-up is characterized by comparable echocardiography parameters. After 1 year of follow-up, patients undergoing pharmaco-invasive treatment with fibrin-specific drugs had significantly higher EF, as well as lower WMSI, iEDV, iESV, and LA size compared to fibrin-nonspecific streptokinase.