A retrospective study involving more than 200 patients has indicated that ‘bridging thrombolysis’ may not be associated with improved functional outcomes in stroke patients who achieve complete recanalisation—as compared to treatment with endovascular therapy (EVT) alone. As such, researchers conclude that their findings encourage ‘direct EVT’ approaches, particularly in patients with a higher likelihood of successful EVT.
Writing in the Journal of Clinical Medicine, Gabriel Broocks (University Medical Center Hamburg-Eppendorf, Hamburg, Germany) and colleagues speculate that significantly increased oedema volume and risk of symptomatic intracerebral haemorrhage (sICH) as secondary injury volumes could be a major reason for a lack of clinical benefit in this patient cohort.
Intravenous thrombolysis (IVT) with alteplase is a standard of care in ischaemic stroke, the authors note, while recent trials investigating direct EVT approaches have shown conflicting results. However, they continue, the effect of IVT on secondary injury volumes in patients with complete recanalisation has not been analysed to date. The researchers therefore hypothesised that IVT is associated with worse functional outcome and aggravated secondary injury volumes when administered to patients who subsequently attained complete reperfusion after EVT.
Broocks and colleagues analysed anterior circulation ischaemic stroke patients with complete post-EVT reperfusion—defined as a thrombolysis in cerebral infarction (TICI) scale score of 3 after thrombectomy—admitted to a single tertiary stroke centre between January 2013 and January 2021. Their study’s primary endpoints were the proportion of patients with functional independence (modified Rankin Scale [mRS] score 0–2 at day 90), and secondary injury volumes, including oedema volume on follow-up imaging—measured using quantitative net water uptake (NWU)—and the rate of sICH.
A total of 219 patients (median age=74 years; 48% female) were included, with 128 of these (58%) receiving bridging IVT with alteplase prior to a thrombectomy. Reporting their results, the authors note that no differences in median National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours were observed between bridging IVT patients and those who received direct EVT (10 vs 13, p=0.75), while median 90-day mRS scores were also similar (4 vs 3, p=0.61).
They detail that the proportion of patients with functional independence was 28% for bridging IVT compared to 34% for direct EVT (p=0.35). And, no significant treatment effect of IVT on functional independence as an endpoint was observed, after regression adjustment for age, NIHSS, Alberta stroke programme early CT score (ASPECTS), occlusion location, and time from onset to imaging (p=0.11), with an adjusted proportion of functional independence of 28% for bridging IVT versus 38% for direct EVT. Patients with bridging IVT had higher total infarct volumes (48ml vs 37ml, p=0.04) and higher oedema volumes (6ml versus 4ml, p=0.039) than those who underwent direct EVT. The rate of sICH was higher in patients with bridging IVT (26% vs 7%, p=0.01), with IVT having a significant effect on the occurrence of sICH (p=0.029) after regression adjustment—indicated by an adjusted proportion of sICH of 19% versus 7.8% in direct EVT patients.
In addition to concluding that IVT was not associated with improved functional outcomes compared to direct EVT, but was significantly and independently associated with increased rates of sICH and oedema volume as secondary injury volumes, the authors state that important predictors of outcome in TICI 3 recanalised patients were age and NIHSS, while ASPECTS, time from onset to imaging, and time from imaging to recanalisation, were not independent predictors. This “emphasises the importance of complete recanalisation as a major determinant of outcome”, they assert.
“To our knowledge, this is the first study that investigated the effect of bridging IVT on functional outcome and secondary injury volumes using quantitative imaging biomarkers in a patient collective exclusively consisting of complete reperfusion cases,” Broocks and colleagues write. “Considering the rising frequency of successful vessel recanalisation over time (e.g. approximately 60% in MR CLEAN, 72% in ESCAPE, 77% in DEFUSE-3, and 86% in ESCAPE-NA1), the importance of optimising treatment strategies for these patients is suggested by the high proportion of patients with poor outcomes despite successful EVT, as described in a recent meta-analysis (i.e. 45% mRS 3–6 in TICI 2b/3). The early identification of stroke patients who might not benefit from IVT could therefore be important to further improve functional outcome. The present study might give further insights into the effect of IVT on lesion pathophysiology in the setting of complete vessel recanalisation, and might help to tailor individual adjuvant treatment options.”
Closing their report, the authors detail limitations of the study, including its retrospective, single-centre nature, and lack of a control group containing patients with incomplete reperfusion, before noting that future studies should analyse the identification of baseline variables to guide IVT, and that further research is necessary to investigate the impact of IVT in relationship to the degree of reperfusion for patients with posterior circulation stroke.