Reteplase 10unit powder and solvent for solution for injection vials

BackgroundThrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and iteration of thrombolytic agents, and the efficacy and adverse effects of different agents have different effects on PE due to their different mechanisms of action.ObjectivesThe aim of the study was to evaluate the efficacy and safety of different thrombolytic agents in the treatment of all types of acute PE: hemodynamically unstable PE (massive PE) and hemodynamically stable PE (submassive PE and low-risk PE), using a network meta-analysis.MethodsA search was conducted of the following databases: PubMed, The Cochrane Library, Embase, and Web of Science to collect randomized controlled trials (RCTs) comparing thrombolytic agents with heparin or other thrombolytic agents in patients with acute PE; the clinical outcomes included patient mortality, recurrent PE, pulmonary artery systolic pressure (PASP) after treatment, and major and minor bleeding. The measurement duration of outcome indicators was the longest follow-up period. Thereafter, a network meta-analysis was performed using a Bayesian network framework.ResultsA total of 29 RCTs (3,067 patients) were included, of which 6 studies (304 patients) were massive PE, 14 studies (2,173 patients) were submassive PE, 1 study (83 patients) included massive and submassive PE, and 8 studies (507 patients) were PE of unknown type. The treatment regimens included thrombolytic therapy (alteplase, reteplase, tenecteplase, streptokinase, and urokinase) and anticoagulant therapy alone. The results showed that the mortality using thrombolytic agents (except tenecteplase) was significantly lower compared with heparin. The recurrence of PE with alteplase was significantly lower compared with heparin (RR = 0.23, 95% CI, 0.04, 0.65). The PASP after using alteplase was significantly lower compared with heparin (mean difference = -11.36, 95% CI, -21.45, -1.56). Compared with heparin, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.27, 95% CI, 1.36, 7.39); compared with streptokinase, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.22, 95% CI, 1.01, 11.10).ConclusionFor patients with acute PE, four thrombolytic agents (alteplase, reteplase, streptokinase, and urokinase) appeared to be superior in efficacy compared with anticoagulants alone due to a reduction in mortality and no increase in bleeding risk. Alteplase may be a better choice because it not only reduced mortality but also reduced PE recurrence rate and treated PASP. Tenecteplase did not reduce mortality compared with anticoagulants alone and may not be a good choice of thrombolytic agent due to an increase in minor bleeding compared with streptokinase and anticoagulants alone. Thrombolytic drugs should be rationally selected to optimize the thrombolytic regimen and achieve as good a balance as possible between thrombolysis and bleeding.

Abstract licence: CC BY-NC

IntroductionThrombolytics are widely used for the treatment of ischaemic stroke. Alteplase is the most commonly used thrombolytic. Newer thrombolytics, particularly tenecteplase and reteplase, are currently available. As such, we performed a network meta-analysis to compare the efficacy of thrombolytic agents.MethodsA systematic search of PubMed MEDLINE, Embase, Scopus and the Cochrane Library was conducted from database inception to 31 August 2024 to identify studies evaluating the efficacy of different thrombolytic agents. Studies analysing thrombolytic effects in terms of mortality or modified Rankin Scale (mRS) in patients with acute ischaemic stroke were included. Comparative efficacy on the two main outcomes was then analysed using a random effects network meta-analysis.ResultsTwenty-three studies were included with a pooled patient cohort of 25,379 patients. In patients with AIS, the network meta-analysis demonstrated no difference in terms of mortality outcomes across the thrombolytics. In terms of functional outcomes, reteplase was associated with a better functional outcome compared to alteplase (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.06, 1.77) and urokinase (OR 1.54, 95% CI 1.14, 2.08). These results were analysed regardless of the duration of follow-up. Further sensitivity analysis based on 90-day follow-up showed no significant differences in terms of mortality outcomes, while reteplase showed similar functional outcomes compared to alteplase and tenecteplase.ConclusionReteplase appeared to be associated with better functional outcomes and had similar mortality rates compared to alteplase. Further head-to-head randomised controlled trials between the thrombolytic agents are needed to confirm these findings.

Abstract licence: CC BY-NC-SA