Mark R. Etherton, MD PhD

Bellwald S, Weber R, Dobrocky T, Nordmeyer H, Jung S, Hadisurya J, et al. Direct Mechanical Intervention Versus Bridging Therapy in Stroke patients Eligible for Intravenous Thrombolysis. Stroke. 2017

In this entry, I discuss the matched pairs analysis of IV tPA eligible patients with large-vessel occlusion (LVO) of the anterior circulation that underwent endovascular thrombectomy (EVT) with or without pre-treatment with IV tPA.

The clinical importance of understanding the role of bridging therapy in patients with LVO is critical for efficaciously triaging this population to stroke centers. The hypothetical scenario is, how should emergency medical services appropriately triage a patient with suspicion for LVO with regards to transfer to a primary stroke center with tPA capabilities or a comprehensive stroke center with EVT capabilities that is further away? This scenario epitomizes why there is great interest in understanding the contribution that bridging therapy with tPA has on outcomes in patients with LVO of the anterior circulation.

In the article by Bellwald et al, the authors explore this question in a retrospective analysis of individual patient data from two studies (Essen and Bernese Stroke registries) comparing outcomes of IV tPA eligible patients that underwent EVT with and without bridging therapy. In the patients that were treated with IV tPA, they received either standard dose (0.9 mg/kg body weight) or 2/3 dose (0.6 mg/kg) within 4.5 hours of symptom onset. In total, 111 IV tPA eligible patients received only EVT and were compared to 249 patients treated with bridging thrombolysis. There was no difference in age, admission NIHSS, vessel occlusion site, endovascular outcome (assessed as TICI 2b-3), sICH, or 90-day rates of good or excellent functional outcomes (assessed as mRS 0-2 or 0-1, respectively). The direct EVT group had higher rates of coronary artery disease (27.1% vs. 16.6%) and decreased time from symptom onset to endovascular treatment (3.23 vs. 4.26 hours; p < 0.001). These findings were similar when subjects in the two groups were matched in a 1:1 fashion based on age, sex, NIHSS, time from symptom onset to diagnosis, occlusion location, and hypertension.

The findings of this article suggest that bridging therapy in IV tPA eligible LVO patients does not significantly impact endovascular outcomes or long-term functional outcomes after EVT. However, there are several limitations of this study, as well as data from other studies that warrant consideration for addressing the larger question. The major strength of this study is that it was an analysis of only IV tPA eligible patients that underwent EVT, whereas other studies have also included IV tPA ineligible patients in their analyses. There are several noteworthy limitations of this study: 1) the lack of information on why the 111 IV tPA eligible patients treated with EVT only were not treated with tPA; 2) the significantly decreased time to endovascular treatment in the EVT only group; and 3) the relatively small sample size and retrospective nature of this study. These results are in direct contrast to a recently published meta-analysis of 13 studies looking at ~1700 LVO patients treated with EVT +/- IV tPA (EA Mistry et al. Stroke 2017), which showed patients treated with bridging therapy had better 90-day functional outcomes (mRS 0-2: OR 1.27; 95% CI 1.05-1.55; P= 0.02), decreased mortality (OR 0.71; 95% CI 0.55-0.91; P=0.006) and better endovascular outcomes. An important distinction in this meta-analysis, however, which limits the comparison to the study discussed here, is that a significant percentage of patients that received direct EVT were not eligible for bridging therapy with IV tPA.

At present, the triage of this population of stroke patients with LVO is predicated on emergent evaluation for treatment with IV tPA and subsequent EVT. Going forward, further data in the form of randomized clinical trials looking at functional outcomes in LVO patients treated with EVT +/- IV tPA, such as SWIFT DIRECT, will be required to answer this question.

Matched case-control analysis (multivariate matching): modified Rankin Scale (mRS) after 3 months.

Figure: Matched case-control analysis (multivariate matching): modified Rankin Scale (mRS) after 3 months.