Early Recanalization Among Patients Undergoing Bridging Therapy With Tenecteplase or Alteplase

Abstract

BACKGROUND: Intravenous thrombolysis (IVT) with alteplase or tenecteplase before mechanical thrombectomy is the recommended treatment for large-vessel occlusion acute ischemic stroke. There are divergent data on whether these agents differ in terms of early recanalization (ER) rates before mechanical thrombectomy, and little data on their potential differences stratified by ER predictors such as IVT to ER evaluation (IVT-to-ER eval ) time, occlusion site and thrombus length. METHODS: We retrospectively compared the likelihood of ER after IVT with tenecteplase or alteplase in anterior circulation large-vessel occlusion acute ischemic stroke patients from the PREDICT-RECANAL (alteplase) and Tenecteplase Treatment in Ischemic Stroke (tenecteplase) French multicenter registries. ER was defined as a modified Thrombolysis in Cerebral Infartion score 2b-3 on the first angiographic run, or noninvasive vascular imaging in patients with early neurological improvement. Analyses were based on propensity score overlap weighting (leading to exact balance in patient history, stroke characteristics, and initial management between groups) and confirmed with adjusted logistic regression (sensitivity analysis). A stratified analysis based on pre-established ER predictors (IVT-to-ER eval time, occlusion site, and thrombus length) was conducted. RESULTS: Overall, 1865 patients were included. ER occurred in 156/787 (19.8%) and 199/1078 (18.5%) patients treated with tenecteplase or alteplase, respectively (odds ratio, 1.09 [95% CI, 0.83–1.44]; P =0.52). A differential effect of tenecteplase versus alteplase on the probability of ER according to thrombus length was observed ( P interaction =0.003), with tenecteplase being associated with higher odds of ER in thrombi >10 mm (odds ratio, 2.43 [95% CI, 1.02–5.81]; P =0.04). There was no differential effect of tenecteplase versus alteplase on the likelihood of ER according to the IVT-to-ER eval time ( P interaction =0.40) or occlusion site ( P interaction =0.80). CONCLUSIONS: Both thrombolytics achieved ER in one-fifth of patients with large-vessel occlusion acute ischemic stroke without significant interaction with IVT-to-ER eval time and occlusion site. Compared with alteplase, tenecteplase was associated with a 2-fold higher likelihood of ER in larger thrombi.

Efficacy and safety of intravenous tenecteplase compared to alteplase before mechanical thrombectomy in acute ischemic stroke: a meta-analysis

“…Regarding study design, this meta-analysis included two RCTs [ 19 , 30 ] and eight non-randomized, non-blind cohort studies [ 16 , 23 – 29 ]. Eight used a prospective approach [ 16 , 19 , 23 – 25 , 27 , 28 , 30 ], while two were based on a retrospective approach [ 26 , 29 ]. Regarding review system, six were peer-reviewed studies [ 19 , 23 – 25 , 28 , 30 ] and four were non-peer-reviewed studies [ 16 , 26 , 27 , 29 ].…”

“…Eight used a prospective approach [ 16 , 19 , 23 – 25 , 27 , 28 , 30 ], while two were based on a retrospective approach [ 26 , 29 ]. Regarding review system, six were peer-reviewed studies [ 19 , 23 – 25 , 28 , 30 ] and four were non-peer-reviewed studies [ 16 , 26 , 27 , 29 ]. The largest sample was included in the study by Checkouri et al (n = 1865) [ 28 ], while Marín et al [ 29 ] had the smallest (n = 18).…”

“…Regarding review system, six were peer-reviewed studies [ 19 , 23 – 25 , 28 , 30 ] and four were non-peer-reviewed studies [ 16 , 26 , 27 , 29 ]. The largest sample was included in the study by Checkouri et al (n = 1865) [ 28 ], while Marín et al [ 29 ] had the smallest (n = 18). Six studies [ 16 , 19 , 23 , 26 , 27 , 29 ] included both anterior and posterior circulation occlusion, three studies [ 25 , 28 , 30 ] focused on anterior circulation occlusion, and one [ 24 ] on posterior circulation occlusion.…”

“…The largest sample was included in the study by Checkouri et al (n = 1865) [ 28 ], while Marín et al [ 29 ] had the smallest (n = 18). Six studies [ 16 , 19 , 23 , 26 , 27 , 29 ] included both anterior and posterior circulation occlusion, three studies [ 25 , 28 , 30 ] focused on anterior circulation occlusion, and one [ 24 ] on posterior circulation occlusion. Thrombolytic doses were highly consistent across studies, using intravenous TNK (0.25 mg/kg) and ALT (0.9 mg/kg).…”

Evolving Clinical–Translational Investigations of Cerebroprotection in Ischemic Stroke

“…Early trials supported these claims with higher recanalization rates [29], but some later studies demonstrated non-inferiority [30,31]. A new study has just demonstrated that TNK may be 2.4-times more effective for early recanalization of thrombi longer than 10 mm in comparison to TPA [32], highlighting how physical clot characteristics may determine the drug choice. Due to time restrictions, only 3-8% of patients are eligible for intravenous clot lysis.…”