Real-world comparative safety and efficacy of tenecteplase versus alteplase in acute ischemic stroke patients with large vessel occlusion

Abstract

Background and aims: Tenecteplase has recently emerged as an alternative thrombolytic agent in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO), possibly superior in achieving early reperfusion compared with alteplase. We aimed to compare the safety and efficacy of intravenous tenecteplase with intravenous alteplase for AIS patients with LVO in everyday clinical practice settings. Methods: We prospectively evaluated patients with AIS due to LVO, treated with intravenous thrombolysis (IVT) with or without mechanical thrombectomy in two tertiary stroke centers. Patients were treated with standard-dose alteplase (0.9 mg/kg) or 0.25 mg/kg tenecteplase. Safety outcomes included prevalence of symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes included averted thrombectomy, major neurological improvement at 24 h (defined as decrease in baseline NIHSS score of 8 points or greater) and functional status on discharge and on 3 months assessed by modified Rankin Scale (mRS). Results: Nineteen AIS patients with LVO received tenecteplase and 39 received alteplase. We observed a non-significant higher rate of averted thrombectomies (32% versus 18%, p = 0.243) and a non-significant higher rate of sICH (16% versus 5%, p = 0.201) in the tenecteplase group. The rate of 24 h major neurological improvement was higher in the tenecteplase group (64% versus 33%, p = 0.046) but this was marginally attenuated in multivariable analyses (adjusted OR 10.22, 95% CI: 0.73–142.98; p = 0.084). Discharge mRS, 3-months mRS, and 3-month functional independence (mRS scores of 0–2) did not differ ( p > 0.2) between the two groups. The rates of 3-month mortality (11% versus 18%, p = 0.703) were similar in the two groups. No independent association between thrombolytic agent and safety or efficacy outcomes emerged in multivariable regression analyses. Conclusion: The present pilot observational study highlights that AIS patients with LVO treated with 0.25 mg/kg bolus administration of tenecteplase had increased likelihood to achieve early neurological improvement compared with AIS patients treated with alteplase, but this association was attenuated after adjustment for potential confounders. There were no significant differences in 3-month functional or safety outcomes between the two groups. This preliminary real-world observation requires independent confirmation in larger, multicenter studies.

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

“…The funnel plots showed that there was no obvious publication bias. However, this meta-analysis also had certain flaws, such as the following: (1) the numbers of included studies and cases were small, which led to instability of the results, as shown in the sensitivity analysis; 6,[31][32][33] (2) the designs of the included studies varied, which may have affected the results; (3) the baseline data, such as sex, age, and NIHSS scores, varied among the studies, 6,7,30 which may have affected the results; and (4) most of the studies included in this analysis were performed in Europe and the United States, and the conclusions may only be generalizable to patients in European and American countries. More high-quality clinical studies in non-European and American countries are needed to clarify the overall efficacy of tenecteplase.…”

“…Additional screening led to the exclusion of 10 meta-analyses 8-17 related to tenecteplase and 12 studies [18][19][20][21][22][23][24][25][26][27][28][29] reporting subgroup analyses of clinical studies and control groups that were not administered alteplase. Ultimately, a total of 9 studies [5][6][7][30][31][32][33][34][35] were included in this meta-analysis, and all of them were published in English. The literature screening process is shown in Figure 1.…”

“…Seven studies [5][6][7][30][31][32][33] reported the proportions of patients with mRS scores of 0-1 at 90 days, and I 2 was 0%, indicating that there was no heterogeneity among the studies; therefore, a fixed-effects model was used. There was no significant difference between the two groups (OR= 1.20, 95% CI: 0.99-1.46, Z=1.82, P =0.07).…”

“…Six studies 6,7,[30][31][32][33]35 reported the incidence of symptomatic intracranial hemorrhage after intravenous thrombolysis, and I 2 was 17%, indicating that there was slight heterogeneity among the studies; therefore the fixed-effects model was used. There was no significant difference between the two groups (OR= 1.27, 95% CI: 0.78-2.07, Z=0.95, P =0.34).…”

“…In recent years, the number of clinical studies comparing the efficacy and safety of tenecteplase and alteplase as intravenous thrombolytic therapies for the treatment of acute ischemic stroke has gradually increased, and most studies have shown that tenecteplase is not inferior in terms of efficacy and safety. Some studies showed that tenecteplase had a certain advantage with regard to improving vascular recanalization and early neurological function, [5][6][7] but the conclusions varied among the studies. Therefore, this analysis was performed to clarify the recent evidence regarding the efficacy and safety of intravenous thrombolysis with tenecteplase.…”