Abstract
In 1995, the results of a landmark clinical trial by National Institute of Neurological Disorders and Stroke (NINDS) made a paradigm shift in managing acute cerebral ischemic stroke (AIS) patients at critical care centers. The study demonstrated the efficacy of tissue-type plasminogen activator (tPA), alteplase in improving neurological and functional outcome in AIS patients when administered within 3 h of stroke onset. After about 12 years of efforts and the results of the ECASS-III trial, it was possible to expand the therapeutic window to 4.5 h, which still represents a major logistic issue, depriving many AIS patients from the benefits of tPA therapy. Constant efforts in this regards are directed toward either speeding up the patient recruitment for tPA therapy or expanding the current tPA window. Efficient protocols to reduce the door-to-needle time and advanced technologies like telestroke services and mobile stroke units are being deployed for early management of AIS patients. Studies have demonstrated benefit of thrombolysis guided by perfusion imaging in AIS patients at up to 9 h of stroke onset, signifying “tissue window.” Several promising pharmacological and non-pharmacological approaches are being explored to mitigate the adverse effects of delayed tPA therapy, thus hoping to further expand the current tPA therapeutic window without compromising safety. With accumulation of scientific data, stroke organizations across the world are amending/updating the clinical recommendations of tPA, the only US-FDA approved drug for managing AIS patients. Alteplase has been a part of our neurocritical care and we intend to celebrate its silver jubilee by dedicating this review article discussing its journey so far and possible future evolution.
Highlights
Acute cerebral stroke is a cerebrovascular disease characterized by an acute compromise of cerebral perfusion or vasculature
Part 1: No significant difference in neurologic improvement at 24 h between the type plasminogen activator (tPA) and placebo group Part 2: Patients treated with tPA we 30% more likely to have no or minimal disability at 3 months after treatment, compared to placebo group ICH was significantly higher in tPA group (p < 0.001) Mortality at 3 months was little lower in tPA group compared to placebo, not significant
Treatment with tPA within 3 h of stroke onset improved the clinical outcome at 3 months in acute cerebral ischemic stroke (AIS) patients, despite an initial increase in ICH incidence
Summary
Acute cerebral stroke is a cerebrovascular disease characterized by an acute compromise of cerebral perfusion or vasculature. AIS patients receiving tPA at 5–6 h of stroke onset demonstrated a significant increase in sICH Due to these safety concerns the window was changed to 0– 5 h and continued as ATLANTIS part-B, the results of which was reported according to two subsets of therapeutic window; 0–3 and 3–5 h [21, 22]. In 2004 a pooled analysis of the data from NINDS, ECASS, and ATLANTIS trials suggested two interesting conclusions: [1] a greater benefit was observed when tPA administered to AIS patients within 90 min of stroke onset, upholding the concept of “sooner the better” and [2] a potential benefit beyond 3 h of tPA administration was observed, with some risks [23] This second conclusion prompted the initiation of ECASS III study, at the request from European regulators, to confirm the benefit of the tPA administration beyond 3 h [3].
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