Pre-Procedural Intravenous Thrombolysis Does Not Change Function and Cognitive Outcome As Long As Thrombectomy is Performed within 6 Hours of Stroke Onset

Direct Thrombectomy versus Bridging Thrombectomy within 6 Hours of Stroke Onset: A Prospective Cohort Study on Cognitive and Physical Function Outcomes

Clinical Question

Are there significant differences in outcomes regarding the physical and cognitive function of patients with acute large vessel occlusion who underwent either direct thrombectomy or bridging thrombectomy (with intravenous thrombolysis prior to thrombectomy)?

Take Away Point

Patients with anterior circulation large vessel occlusions treated within 6 hours of symptom onset demonstrated comparable outcomes regarding physical and cognitive function with both direct thrombectomy or bridging thrombectomy.

Reference

Direct Thrombectomy versus Bridging Thrombectomy within 6 Hours of Stroke Onset: A Prospective Cohort Study on Cognitive and Physical Function Outcomes. Li, Bing-Hu et al. Journal of Vascular and Interventional Radiology, Volume 34, Issue 11, P1875-1881, 10.1016/j.jvir.2023.07.008

Study Design

Prospective, observational, cohort study

Funding Source

This study was supported by grants from Department of Sichuan Provincial Science and Technology and Bureau of Chengdu Science and Technology.




Figure 2
Comparison of modified Rankin Scale between direct thrombectomy and bridging thrombectomy

Setting

Academic Medical Center, Chengdu, China

Summary

Acute ischemic strokes (AIS) account for 69.6% of all strokes in China, with endovascular thrombectomy being the standard and effective treatment for patients with large vessel occlusion (LVO). However, the question of whether intravenous thrombolysis before endovascular thrombectomy has a role in patients with acute anterior circulation LVO remains controversial. Recognizing the inconsistent data and limited data on bridging thrombectomy’s effects on cognitive function, the authors conducted this prospective study to assess both physical and cognitive function in anterior circulation LVO patients undergoing direct or bridging thrombectomy within 6 hours of stroke onset.

A total of 125 patients with LVO of the anterior circulation, including the intracranial internal carotid, middle cerebral artery segment 1 and/or segment 2, were confirmed by computed tomography angiography (CTA) or digital subtraction angiography (DSA) and included in the study. The median age of the patients was 71.0 (24.0-95.0) years, and among them 60 were men. The median time interval between stroke onset and reperfusion was 348 minutes (150 - 1,295). Patients in the bridging group underwent thrombectomy after receiving a standard dose of intravenous alteplase (0.9mg/kg; 10% as a bolus followed by a 1-hour infusion) within 4.5 hours or intravenous urokinase (1,000,000-1,500,000 units) within 6 hours. Meanwhile, patients in the direct group solely underwent thrombectomy.

The study assessed physical function at the 3-month mark using the Modified Rankin Score (mRS), a 7-point global disability scale that ranges from 0 (no symptoms) to 7 (death). Cognitive function was evaluated at the 6-month mark using the Clinical Dementia Rating (CDR), which ranges from 0 to 3. A score of 0 indicating absence of symptoms, 0.5 indicating questionable dementia, 1 indicating mild dementia, 2 indicating moderate dementia, and 3 indicating severe dementia. Both mRS and CDT assessments were performed via telephone calls by two trained neurologists using a blinded method. Symptomatic intracranial hemorrhage (sICH) was defined as the presence of intracranial hemorrhage with neurologic deterioration of 4 or more points on the NIH stroke scale.

The study included 75 patients in the direct group and 50 patients in the bridging group. The study determined that the direct group exhibited shorter reperfusion times (323.0 [160.0-820.0 minutes) compared to the bridging group (390.0 [150.0-1,295.0] minutes). Analysis of the results found no statistically significant differences between the direct and bridging groups in terms of the percentage of patients with an mRS score of 0-2 (25.3% vs 22.0%, P=.83.) or 0-3 (37.3% vs 44.0%, P=.58), the incidence of sICH within 24 hours (17.3% vs 14.0%, P=.80), or 90-day all-cause mortality rates (36.3% vs 30.0%, P=.34). Furthermore, the proportion of patients with normal cognition at 6 months was comparable between the direct and bridging group. Additionally, the proportion of patients with post-stroke dementia was comparable between the direct and bridging groups (42.1% vs 22.6%, P=.12).

Conflicting outcomes from various RCTs has resulted in an ongoing debate surrounding whether intravenous thrombolysis should precede thrombectomy for acute LVO strokes. While some previously published studies favor direct thrombectomy, others conclude that direct thrombectomy is noninferior to bridging thrombectomy. This prospective cohort study demonstrated that both direct thrombectomy and bridging thrombectomy have comparable physical function outcomes. Additionally, the study demonstrated that the bridging group observed a trend of lower cognitive impairment, however, the results were not statistically significant. The authors noted that the presence of diabetes was associated with a lower CDR score, suggesting a potential influence of antidiabetic drugs on preserving cognitive function. Overall, the study findings indicate that direct thrombectomy is comparable to bridging thrombectomy in patients with acute LVO strokes treated within 6 hours in regards to physical and cognitive function.

Commentary

The study was appropriately designed and executed effectively. While the original sample size was appropriate, the study experienced a considerable number of deaths and losses to follow-up in both treatment groups, impacting the power of the study. The authors employed appropriate statistical tests, including the X2, Fischer exact test, and Mann-Whitney U test, to analyze the data. Given the conflicting results in the published literature regarding direct and bridging thrombectomy for the treatment of LVO strokes, this study aimed to compare the effects of both treatment modalities on physical and cognitive function to determine their relative efficacy. Although the study did not definitively establish a superior treatment modality it effectively demonstrated that both treatment options are comparable. The results, while not statistically significant, offer convincing data that could potentially impact clinical decision-making. Ultimately, the paper provides valuable evidence that can contribute to the ongoing discussion about the management of patients with acute LVO strokes. However, further research with a more robust study design, such as an RCT, a larger sample size, a more diverse patient population, and more diversity in clinical sites, could lead to more robust conclusions and potentially significant changes in patient care.

Post Author 

Aric Patel, MS
OMS-IV
University of New England
College of Osteopathic Medicine