Abstract
In the treatment of acute ischemic stroke (AIS), vessel recanalization correlates with improved functional status and reduced mortality. Mechanical neurothrombectomy achieves a higher likelihood of revascularization than intravenous thrombolysis (IVT), but there remains significant discrepancy between rates of recanalization and rates of favorable outcome. The poor neurological recovery among some stroke patients despite successful recanalization confirms the need for adjuvant therapy, such as pharmacological neuroprotection. Prior clinical trials of neuroprotectant drugs failed perhaps due to inability of the agent to reach the ischemic tissue beyond the occluded artery. A protocol that couples mechanical neurothrombectomy with concurrent delivery of a neuroprotectant overcomes this pitfall. Activated protein C (APC) exerts pleiotropic anti-inflammatory, anti-apoptotic, antithrombotic, cytoprotective, and neuroregenerative effects in stroke and appears a compelling candidate for this novel approach.
Highlights
Reviewed by: Lei Liu, University of Florida, College of Medicine, USA Richard F
Mechanical neurothrombectomy achieves a higher likelihood of revascularization than intravenous thrombolysis (IVT), but there remains significant discrepancy between rates of recanalization and rates of favorable outcome
Despite extensive research into the pathophysiology underlying acute ischemic stroke (AIS), intravenous tissue plasminogen activator (IV Tissue plasminogen activator (tPA)) remains the only drug approved by the United States Food and Drug Administration (FDA) for its treatment
Summary
Data from intravenous thrombolysis (IVT) trials serve as the benchmark against which recanalization therapies such as neurothrombectomy are measured. The seminal National Institute of Neurological Disorders and Stroke (1995) trial reported favorable results that formed the basis for FDA approval of IV tPA in AIS. There was a powerful and statistically significant benefit shown: at 3 months, the odds ratio for favorable outcome was 1.7 in the tPA group as compared with placebo. There was no statistically significant difference between the group given tPA and that given placebo in the percentage of patients who showed a 4-point neurological improvement at 24 h (47 vs 39% respectively, p = 0.06), using any other cut point yielded a highly significant benefit at 24 h (Haley et al, 1997). A long-term benefit 1 year later was observed for the tPA group using a global test statistic that represents a composite of other scales, including modified Rankin score
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