Abstract
Ischemic stroke is the most widespread cause of disability and a leading cause of death in developed countries. To date, the most potent approved treatment for acute stroke is recanalization therapy with thrombolytic drugs such as tissue plasminogen activator (rt-PA or tPA) or endovascular mechanical thrombectomy. Although tPA and thrombectomy are widely available in the United States, it is currently estimated that only 10–20% of stroke patients get tPA treatment, in part due to restrictive selection criteria. Recently, however, tPA and thrombectomy selection criteria have loosened, potentially allowing more patients to qualify. The relatively low rate of treatment may also reflect the perceived risk of brain hemorrhage following treatment with tPA. In translational research and a single patient study, protease activated receptor 1 (PAR-1) targeted therapies given along with thrombolysis and thrombectomy appear to reduce hemorrhagic transformation after recanalization. Such adjuncts may likely enhance the availability of recanalization and encourage more physicians to use the recently expanded selection criteria for applying recanalization therapies. This narrative review discusses stroke therapies, the role of hemorrhagic transformation in producing poor outcomes, and presents the data suggesting that PAR-1 acting agents show promise for decreasing hemorrhagic transformation and improving outcomes.
Highlights
Each year about 795,000 people in the United States experience a stroke [1]
Recanalization therapy with thrombolytic drugs such as recombinant tissue plasminogen activator is the most common treatment for acute stroke. tPA is approved for intravenous administration within 3 h of onset of acute ischemic stroke in the United States and for up to 4.5 h following the stroke in Europe [1, 18]
The National Institute of Neurological Disorders and Stroke (NINDS) trials, defined symptomatic intracranial hemorrhage (SICH) as “any hemorrhagic transformation temporally related to any worsening in neurologic condition [30].”Over the 2 decades, this definition was recognized as over-inclusive
Summary
Each year about 795,000 people in the United States experience a stroke [1]. Of all types of stroke, 87% are ischemic (i.e., caused by an interruption of blood supply), 10% are intracerebral hemorrhage strokes (i.e., caused by a ruptured blood vessel), and 3% are subarachnoid hemorrhage strokes (bleeding into the outermost layer of the brain) [2]. Stroke continues to be a major public health concern despite significant previous research that has produced treatment approaches addressing acute reperfusion and revascularization [12,13,14], neuronal protection [12], and regeneration of damaged brain tissue [15, 16] All these tactics were based on scientific principles and preclinical data, yet no candidate cytoprotective therapy has successfully entered clinical practice [15]. It is clear that single-action, single-target agents fail to treat stroke because ischemia produces a combination of pathologic pathways proceeding in parallel that damage neural tissue [17] This narrative review presents a discussion of stroke therapies, the role of hemorrhagic transformation in producing poor outcomes, and presents the data suggesting that PAR-1 acting agents show promise for decreasing hemorrhagic transformation and improving outcomes. In patients without documented large vessel occlusion, thrombolytic therapy alone is generally sufficient to reperfuse the microvasculature
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