Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trials
ObjectiveTo systematically compare the benefits and risks of all thrombolytic agents (tenecteplase, reteplase, and alteplase) at different doses for thrombolytic therapy in patients with acute ischemic stroke (AIS).BackgroundAlteplase is the cornerstone treatment for AIS, but alternative thrombolyti...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1490476/full |
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| author | Li-Chao-Yue Sun Wen-Shu Li Wei Chen Zhao Ren Chun-Xing Li Ze Jiang Le Wang De-Li Wang Qing Xie |
| author_facet | Li-Chao-Yue Sun Wen-Shu Li Wei Chen Zhao Ren Chun-Xing Li Ze Jiang Le Wang De-Li Wang Qing Xie |
| author_sort | Li-Chao-Yue Sun |
| collection | DOAJ |
| description | ObjectiveTo systematically compare the benefits and risks of all thrombolytic agents (tenecteplase, reteplase, and alteplase) at different doses for thrombolytic therapy in patients with acute ischemic stroke (AIS).BackgroundAlteplase is the cornerstone treatment for AIS, but alternative thrombolytic agents are needed. The efficacy and safety of tenecteplase and reteplase, compared to alteplase, remain unclear, as does the optimal dosing for these treatments.MethodA systematic search was conducted in PubMed, Web of Science, SCOPUS, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant English-language studies up to July 5, 2024. Randomized controlled trials (RCTs) comparing standard-dose alteplase with varying doses of tenecteplase or reteplase in AIS patients were included. Primary outcomes were functional outcome at 90 days, symptomatic intracranial hemorrhage, death within 90 days, and serious adverse events. Data on study characteristics, patient demographics, interventions, and outcomes were extracted, and bias risk assessed. A multivariate random-effects model was used for network meta-analysis to derive odds ratios (OR) and 95% confidence intervals (CI).ResultTwelve RCTs were included (10 with tenecteplase, 2 with reteplase) involving 6,633 patients, all compared against 0.9 mg/kg alteplase. In comparison with alteplase, tenecteplase demonstrated OR of 1.08 for achieving an excellent functional outcome at 90 days (95% CI: 0.97 to 1.22, P = 0.17). Reteplase, on the other hand, showed a significantly higher OR of 1.55 for the same outcome (95% CI: 1.23 to 1.95, P = 0.0002). Reteplase at 18 mg + 18 mg (OR 1.6, 95% CI: 0.91–2.5) showed a higher probability of achieving an excellent functional outcome at 90 days compared to alteplase. When considering a good functional outcome at 90 days, tenecteplase had an OR of 1.03 (95% CI: 0.81 to 1.3, P = 0.82), while reteplase had an OR of 1.15 (95% CI: 0.61 to 2.19, P = 0.66). Tenecteplase at 0.25 mg/kg (OR 1.3, 95% CI: 0.79–2.5) had the highest probability of achieving a good functional outcome at 90 days. For safety outcomes, 0.25 mg/kg tenecteplase had lower incidences of symptomatic intracranial hemorrhage (OR 0.88, 95% CI: 0.35–1.8), death within 90 days (OR 0.91, 95% CI: 0.54–1.4), and serious adverse events (OR 1.0, 95% CI: 0.47–2.3) compared to alteplase, though differences were not statistically significant. Reteplase at 18 mg + 18 mg had higher incidences of death within 90 days (OR 1.2, 95% CI: 0.48–3) and serious adverse events (OR 1.4, 95% CI: 0.4–5.0) compared to alteplase, without significant differences. Subgroup analysis showed better efficacy with 0.25 mg/kg tenecteplase in Asians (OR 1.18, 95% CI 0.96–1.45, P = 0.12) than in Caucasians (OR 1.08, 95% CI 0.9–1.3, P = 0.39).ConclusionThis study suggests that tenecteplase and reteplase are viable alternatives to alteplase for thrombolysis in AIS. Tenecteplase at 0.25 mg/kg and reteplase at 18 mg + 18 mg may offer better efficacy compared to standard-dose alteplase, although the risk of adverse events with reteplase should be considered. Tenecteplase at 0.25 mg/kg appears to provide the best benefit-risk profile based on current evidence. Further head-to-head trials of tenecteplase and reteplase are needed to determine the optimal thrombolytic agent and dosing.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO CRD42024566146. |
| format | Article |
| id | doaj-art-9f77eb3bcfe94e878dc639e065d91219 |
| institution | Kabale University |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj-art-9f77eb3bcfe94e878dc639e065d912192025-01-07T05:23:55ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-01-011510.3389/fneur.2024.14904761490476Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trialsLi-Chao-Yue Sun0Wen-Shu Li1Wei Chen2Zhao Ren3Chun-Xing Li4Ze Jiang5Le Wang6De-Li Wang7Qing Xie8Department of Pharmacy, Aerospace Center Hospital, Beijing, ChinaDepartment of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, Emergency General Hospital, Beijing, ChinaDepartment of Pharmacy, Aerospace Center Hospital, Beijing, ChinaDepartment of Pharmacy, Aerospace Center Hospital, Beijing, ChinaDepartment of Pharmaceutical, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Pharmaceutical, Sichuan Taikang Hospital, Chengdu, Sichuan, ChinaDepartment of Pharmacy, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, ChinaDepartment of Pharmacy, Aerospace Center Hospital, Beijing, ChinaObjectiveTo systematically compare the benefits and risks of all thrombolytic agents (tenecteplase, reteplase, and alteplase) at different doses for thrombolytic therapy in patients with acute ischemic stroke (AIS).BackgroundAlteplase is the cornerstone treatment for AIS, but alternative thrombolytic agents are needed. The efficacy and safety of tenecteplase and reteplase, compared to alteplase, remain unclear, as does the optimal dosing for these treatments.MethodA systematic search was conducted in PubMed, Web of Science, SCOPUS, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant English-language studies up to July 5, 2024. Randomized controlled trials (RCTs) comparing standard-dose alteplase with varying doses of tenecteplase or reteplase in AIS patients were included. Primary outcomes were functional outcome at 90 days, symptomatic intracranial hemorrhage, death within 90 days, and serious adverse events. Data on study characteristics, patient demographics, interventions, and outcomes were extracted, and bias risk assessed. A multivariate random-effects model was used for network meta-analysis to derive odds ratios (OR) and 95% confidence intervals (CI).ResultTwelve RCTs were included (10 with tenecteplase, 2 with reteplase) involving 6,633 patients, all compared against 0.9 mg/kg alteplase. In comparison with alteplase, tenecteplase demonstrated OR of 1.08 for achieving an excellent functional outcome at 90 days (95% CI: 0.97 to 1.22, P = 0.17). Reteplase, on the other hand, showed a significantly higher OR of 1.55 for the same outcome (95% CI: 1.23 to 1.95, P = 0.0002). Reteplase at 18 mg + 18 mg (OR 1.6, 95% CI: 0.91–2.5) showed a higher probability of achieving an excellent functional outcome at 90 days compared to alteplase. When considering a good functional outcome at 90 days, tenecteplase had an OR of 1.03 (95% CI: 0.81 to 1.3, P = 0.82), while reteplase had an OR of 1.15 (95% CI: 0.61 to 2.19, P = 0.66). Tenecteplase at 0.25 mg/kg (OR 1.3, 95% CI: 0.79–2.5) had the highest probability of achieving a good functional outcome at 90 days. For safety outcomes, 0.25 mg/kg tenecteplase had lower incidences of symptomatic intracranial hemorrhage (OR 0.88, 95% CI: 0.35–1.8), death within 90 days (OR 0.91, 95% CI: 0.54–1.4), and serious adverse events (OR 1.0, 95% CI: 0.47–2.3) compared to alteplase, though differences were not statistically significant. Reteplase at 18 mg + 18 mg had higher incidences of death within 90 days (OR 1.2, 95% CI: 0.48–3) and serious adverse events (OR 1.4, 95% CI: 0.4–5.0) compared to alteplase, without significant differences. Subgroup analysis showed better efficacy with 0.25 mg/kg tenecteplase in Asians (OR 1.18, 95% CI 0.96–1.45, P = 0.12) than in Caucasians (OR 1.08, 95% CI 0.9–1.3, P = 0.39).ConclusionThis study suggests that tenecteplase and reteplase are viable alternatives to alteplase for thrombolysis in AIS. Tenecteplase at 0.25 mg/kg and reteplase at 18 mg + 18 mg may offer better efficacy compared to standard-dose alteplase, although the risk of adverse events with reteplase should be considered. Tenecteplase at 0.25 mg/kg appears to provide the best benefit-risk profile based on current evidence. Further head-to-head trials of tenecteplase and reteplase are needed to determine the optimal thrombolytic agent and dosing.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO CRD42024566146.https://www.frontiersin.org/articles/10.3389/fneur.2024.1490476/fullacute ischemic strokealteplasetenecteplasereteplasenetwork meta-analysis |
| spellingShingle | Li-Chao-Yue Sun Wen-Shu Li Wei Chen Zhao Ren Chun-Xing Li Ze Jiang Le Wang De-Li Wang Qing Xie Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trials Frontiers in Neurology acute ischemic stroke alteplase tenecteplase reteplase network meta-analysis |
| title | Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trials |
| title_full | Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trials |
| title_fullStr | Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trials |
| title_full_unstemmed | Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trials |
| title_short | Thrombolytic therapy for patients with acute ischemic stroke: systematic review and network meta-analysis of randomized trials |
| title_sort | thrombolytic therapy for patients with acute ischemic stroke systematic review and network meta analysis of randomized trials |
| topic | acute ischemic stroke alteplase tenecteplase reteplase network meta-analysis |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1490476/full |
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