Debunking 7 Myths That Hamper the Realization of Randomized Controlled Trials on Intra-Arterial Thrombolysis for Acute Ischemic Stroke

Ciccone, Alfonso; Valvassori, Luca; Gasparotti, Roberto; Scomazzoni, Francesco; Ballabio, E.; Sterzi, Roberto

doi:10.1161/strokeaha.106.465567

Cited by 44 publications

(30 citation statements)

References 42 publications

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“…As such, reperfusion may be followed by different clinical scenarios, including neurologic improvement, worsening, and even death related to reperfusion brain edema and/or ICH. 9 Overall, the revascularization rates described in the literature are higher with IA than IV thrombolysis. 8,9 In angiographic and transcranial Doppler sonographic controlled trials of IV rtPA, partial or complete recanalization of middle cerebral artery (MCA) occlusions has been reported in approximately one third of the patients 10-13 compared with two thirds of patients with IA recombinant pro-UK (rpro-UK) and IV heparin in the Prolyse in Acute Cerebral Thromboembolism II (PROACT II) trial.…”

mentioning

confidence: 97%

Endovascular Approaches to Acute Stroke, Part 2: A Comprehensive Review of Studies and Trials

Nogueira¹,

Yoo²,

Buonanno³

et al. 2009

AJNR Am J Neuroradiol

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SUMMARY:Reperfusion remains the mainstay of acute ischemic stroke treatment. Endovascular therapy has become a promising alternative for patients who are ineligible for or have failed intravenous (IV) thrombolysis. The conviction that recanalization of properly selected patients is essential for the achievement of good clinical outcomes has led to the rapid and widespread growth in the adoption of endovascular stroke therapies. However, comparisons of the recent reperfusion studies have brought into question the strength of the association between revascularization and improved clinical outcome. Despite higher rates of recanalization, the mechanical thrombectomy studies have demonstrated substantially lower rates of good outcomes compared with IV and/or intra-arterial thrombolytic trials. However, such analyses disregard important differences in clot location and burden, baseline stroke severity, time from stroke onset to treatment, and patient selection in these studies. Many clinical trials are testing novel devices and drugs as well as the paradigm of physiology-based stroke imaging as a treatment-selection tool. The objective of this article is to provide a comprehensive review of the relevant past, current, and upcoming data on endovascular stroke therapy with a special focus on the prospective studies and randomized clinical trials. Mirroring its intravenous (IV) counterpart, much of the early work in endovascular stroke therapy has been reported in nonrandomized case series. Reports of successful intra-arterial thrombolysis (IAT) date back to the late 1950s, when Sussmann and Fitch 1 described the recanalization of an acutely occluded internal carotid artery (ICA) with intra-arterial (IA) injection of plasmin. Although pioneering work continued, it was not until the early 1990s that IAT was studied in a more systematic manner. In 2002, Lisboa et al 2 published a meta-analysis regarding the safety and efficacy of this approach. They performed a meta-analysis of 27 studies (minimum of 10 patients in each) with a total of 852 patients who had received IAT and 100 control subjects, in the era before the mechanical thrombectomy trials.3-5 There were more favorable outcomes in the IAT group than in the control group (41.5% versus 23%, P ϭ .002), with a lower mortality rate for IAT (27.2% versus 40%, P ϭ .004). The IAT group had an odds ratio (OR) of 2.4 (95% confidence interval [CI,], 1.45-3.85) for favorable outcome, despite a higher frequency of symptomatic intracranial hemorrhage (SICH; 9.5% versus 3%, P ϭ .046). In addition, they found a trend toward better outcomes with combined IV recombinant tissue plasminogen activator (rtPA) and IAT than with IAT alone. They also remarked that IAT-treated supratentorial strokes were more likely to have favorable outcomes than infratentorial ones (42.2% versus 25.6%, P ϭ .001; OR, 2.0; 95% CI, 1.33-3.0).A recent retrospective study compared 144 patients treated with IAT by using urokinase (UK) within 6 hours of symptom onset versus 147 patients treated with aspirin (250...

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mentioning

confidence: 97%

Endovascular Approaches to Acute Stroke, Part 2: A Comprehensive Review of Studies and Trials

Nogueira¹,

Yoo²,

Buonanno³

et al. 2009

AJNR Am J Neuroradiol

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“…27 The high rate of recanalization with endovascular treatment might give the impression that this method is effective in most cases, although it may provide no clinical benefit in almost half the patients. 28 This trial did not show that endovascular therapy achieves superior outcomes as compared with intravenous thrombolysis, and our findings do not provide support for the use of the more invasive and expensive endovascular therapy over intravenous treatment.…”

Section: Figure 2 (Facing Page) Effect Of Treatment On the Primary Omentioning

confidence: 99%

Endovascular Treatment for Acute Ischemic Stroke

Arnold¹,

Schroth²,

Gralla³

2013

N Engl J Med

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“…Questions remain over the safety and efficacy of IAT compared with intravenous rt-PA. Most reports of safety with IAT come from case series [Ciccone et al 2007].…”

Section: Intra-arterial Thrombolysismentioning

confidence: 99%

Thrombolysis in acute ischaemic stroke: an update

Robinson

Zaheer

Mistri

2011

Therapeutic Advances in Chronic Disease

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Stroke is a major cause of mortality and morbidity, and thrombolysis has served as a catalyst for major changes in the management of acute ischaemic stroke. Intravenous alteplase (recombinant tissue plasminogen activator) is the only approved thrombolytic agent at present indicated for acute ischaemic stoke. While the licensed time window extends to 3 h from symptom onset, recent data suggest that the trial window can be extended up to 4.5 h with overall benefit. Nonetheless, 'time is brain' and every effort must be made to reduce the time delay to thrombolysis. Intracranial haemorrhage is the major complication associated with thrombolysis, and key factors increasing risk of haemorrhage include increasing age, high blood pressure, diabetes and stroke severity. Currently, there is no direct evidence to support thrombolysis in patients >80 years of age, with a few case series indicating no overt harm. Identification of viable penumbra based on computed tomography/magnetic resonance imaging may allow future extension of the time window. Adjuvant transcranial Doppler ultrasound has the potential to improve reperfusion rates. While intra-arterial thrombolysis has been in vogue for a few decades, there is no clear advantage over intravenous thrombolysis. The evidence base for thrombolysis in specific situations (e.g. dissection, pregnancy) is inadequate, and individualized decisions are needed, with a clear indication to the patient/carer about the lack of direct evidence, and the riskbenefit balance. Patient-friendly information leaflets may facilitate the process of consent for thrombolysis. This article summarizes the recent advances in thrombolysis for acute ischaemic stroke. Key questions faced by clinicians during the decision-making process are answered based on the evidence available.

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Debunking 7 Myths That Hamper the Realization of Randomized Controlled Trials on Intra-Arterial Thrombolysis for Acute Ischemic Stroke

Cited by 44 publications

References 42 publications

Endovascular Approaches to Acute Stroke, Part 2: A Comprehensive Review of Studies and Trials

Endovascular Approaches to Acute Stroke, Part 2: A Comprehensive Review of Studies and Trials

Endovascular Treatment for Acute Ischemic Stroke

Thrombolysis in acute ischaemic stroke: an update

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