Introduction: The use of alteplase (ALT) bridging to endovascular mechanical thrombectomy (MT) has become the standard approach in treating patients with large vessel occlusion (LVO) stroke. Tenecteplase (TNK) has emerged as an equivalent fibrinolytic agent in treating ischemic stroke due to its remarkable pharmacological characteristics. This study aimed to compare the use of intravenous TNK to ALT bridging to MT in patients with LVO. Methods: We included observational and randomized controlled trials of patients with LVO who received bridging TNK versus ALT before undergoing MT. Efficacy outcomes included functional independence which is indicated by a modified Rankin Scale [mRS] score of 0–2 at 90 days. Radiological outcomes included the rate of successful recanalization post-MT (Modified Treatment in Cerebral Ischemia [mTICI] score of 2b/3) and the rate of pre-MT recanalization, indicated by an mTICI of 2b/3 at the first angiographic assessment. The all-cause mortality at 90 days (mRS of 6) was considered the primary safety outcome, while the symptomatic intracranial hemorrhage rate was reported as an adverse event. Results: We identified 5 comparative observational studies and 1 randomized controlled trial, totaling 4,186 patients with LVO. The crude odds ratio (OR) for post-MT recanalization in patients with LVO who received TNK was comparable to those who received ALT (OR = 1.14; 95% CI: 0.57–2.27, I2 = 54%). The rate of pre-MT recanalization was significantly higher in those given TNK as a bridging therapy to MT compared to those who received ALT (OR = 2.66; 95% CI: 1.60–4.41, I2 = 0%; p <0.001). Functional independence at 90 days was not significantly different between patients with stroke who received TNK and those who were given ALT before MT (OR = 1.41; 95% CI: 0.84–2.35; I2 = 45%). The 90-day mortality was similar between patients with LVO who received TNK and those who were given ALT prior to undergoing MT (OR = 0.74; 95% CI: 0.46–1.21; I2 = 0%). Conclusion: Patients with LVO who received TNK as the primary fibrinolytic agent bridging to MT demonstrated higher rates of pre-MT recanalization, similar rates in post-MT recanalization and equivalent functional independence outcomes at 90 days compared to those who received ALT. The administration of TNK before MT showed comparable results in the 90-day all-cause mortality rate compared to those who received ALT. These results warrant further trials for TNK to be used as a superior fibrinolytic agent to ALT in LVO-MT candidates.

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