Reflection on the Past, Present, and Future of Thrombolytic Therapy for Acute Ischemic Stroke

Demel, Stacie L; Stanton, Robert J.; Aziz, Yasmin; Adeoye, Opeolu; Khatri, Pooja

doi:10.1212/wnl.0000000000012806

Cited by 9 publications

(6 citation statements)

References 62 publications

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“…and continuously optimized. 5 No such widely adopted time-based metrics currently exist for ICH (Figure 1).…”

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confidence: 99%

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Code ICH: A Call to Action

Li,

Yakhkind,

Alexandrov

et al. 2024

Stroke

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Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

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“…and continuously optimized. 5 No such widely adopted time-based metrics currently exist for ICH (Figure 1).…”

mentioning

confidence: 99%

“…Quality metrics including door-to-needle and door-to-groin puncture time are measured, reported, and continuously optimized. 5 No such widely adopted time-based metrics currently exist for ICH (Figure 1).…”

mentioning

confidence: 99%

Code ICH: A Call to Action

Li,

Yakhkind,

Alexandrov

et al. 2024

Stroke

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“…With endovascular therapy advances, multiple studies are investigating whether thrombolytic therapy can be bypassed in patients with LVO, where initial presentation is at thrombectomy or comprehensive stroke centers, in order to be treated with primary MT, as the case of acute myocardial infarction. To date, these studies have failed to provide any shared results and not one of these studies has reported an overall noninferiority when compared to combined treatment [180]. Moreover, the use of advanced neuroimaging techniques could allow the evaluation of collateral circulation status before and after revascularization strategies, to more consciously guide the management of AIS patients and reduce the rate of “futile recanalization,” as well as the design of clinical trials on interventions having collateral circulation as target to obtain a better clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

Treatments in Ischemic Stroke: Current and Future

Mosconi¹,

Paciaroni²

2022

Eur Neurol

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Background and Aim: Despite progress made over the last 30 years, stroke is still a leading cause of disability and mortality; likewise, its burden is expected to increase over the next decades, due to population growth and aging. The development of drugs with better safety-efficacy profiles as well as strategies able to improve ischemic stroke management from the pre-hospital setting is needed. Summary: The pathophysiology of ischemic stroke involves multiple pathways resulting in cerebral artery obstruction and brain tissue ischemia. To date, the only approved drug for acute ischemic stroke is intravenous thrombolytic alteplase. Intravenous thrombolysis (IVT) can be administered alone or in combination with endovascular treatment (EVT) with mechanical thrombectomy, in case of large vessel occlusion and generally within 6 h from symptoms onset. The risk of potential bleeding complications, especially symptomatic intracerebral hemorrhage, is one of the reasons for the reluctance to administer IVT. Tenecteplase is a promising alternative fibrinolytic agent, having a better safety profile than alteplase. Moreover, recent evidences have allowed an extension of the IVT ± EVT time window for patients with unknown onset time and for those with a known onset time thanks to the new “tissue-window” approach guided by advanced neuroimaging techniques, which also helps in collateral circulation estimation. Regarding primary-secondary prevention, researchers are focused on improving the efficacy of antithrombotic drugs with a “hemostasis-sparing” approach. Neuroprotective agents are also under development, particularly stem cells. The COVID-19 pandemic has critically stressed global healthcare systems, with collateral damage resulting in access delivery of only emergency care, such as ischemic stroke. Regarding telemedicine, it has had a minor role in acute stroke management, and with the onset of COVID-19, this role will most likely be adopted to increase access and delivery in stroke assessment, but also in the follow-up.

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“…EVT has been a critical advance in the management of LVO, but there is a continued role for thrombolysis in a subset of patients. Demel et al 28 investigate the opportunity for novel or adjunctive IV pharmacologic agents to achieve reperfusion. Specifically, safer and more efficacious drugs may allow for faster delivery of therapy (particularly when EVT is not immediately available) as well as facilitate recanalization (particularly of more distal occlusions).…”

Section: Treatments: Lytics and Neuroprotectionmentioning

confidence: 99%

The Neurointerventional Revolution

et al. 2021

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Purpose of the ReviewIn a short period of time, the field of interventional neurology has been transformed. Supported by strong Class IA evidence, the vascular and interventional neurology community has been empowered to realign systems of care to address the new challenges that have been introduced. Given the recent developments and accelerating pace of the field, the Society of Vascular and Interventional Neurology has collaborated with the American Academy of Neurology to provide an updated supplemental edition of Neurology® focused on endovascular therapy for acute ischemic stroke.Recent FindingsIn this supplemental edition, the authors discuss the unmet need for endovascular therapy, emerging trends in stroke systems of care, the role of imaging in patient selection, prognostication and treatment-related factors, procedural considerations, current top tier guidelines, recent advances in neuroprotection, and future directions of the field.SummaryThe field of interventional neurology continues to grow and advance, particularly since the seminal stroke trials published between 2015 and 2018. Whereas this progress has significantly improved the ability to alter outcomes after acute ischemic stroke due to large vessel occlusion, important new hurdles present themselves to the neurology community.

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Reflection on the Past, Present, and Future of Thrombolytic Therapy for Acute Ischemic Stroke

Cited by 9 publications

References 62 publications

Code ICH: A Call to Action

Code ICH: A Call to Action

Treatments in Ischemic Stroke: Current and Future

The Neurointerventional Revolution

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