Progress in Intravenous Thrombolytic Therapy for Acute Stroke

Marshall, Randolph S.

doi:10.1001/jamaneurol.2015.0835

Cited by 76 publications

(59 citation statements)

References 35 publications

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“…Similar efficacy was observed between the two doses in regards to common carotid blood flow restoration, suggesting that low dose can be used safely for restoration of flow in large arterial vessels but not in the smaller in diameter ones. The latter is important for ischemic strokes where the combination of thrombolysis and interventional techniques is the currently preferable treatment [25].…”

Section: Discussionmentioning

confidence: 99%

Low dose tenecteplase restores vessel patency in a clinically relevant porcine animal model

Tseliou¹,

Ntalianis²,

Diakos³

et al. 2016

J Transl Sci

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Thrombolysis remains the treatment of choice in patients who are far from the catheterization laboratories. Although full dose is advisable low dose has not been preclinically tested. Here we tested the hypothesis that low dose tenecteplase, a recombinant fibrin-specific plasminogen activator can induce efficient thrombolysis even in lower doses than the hitherto indicated, compared to full-dose thrombolytic therapy for ST-segment myocardial infarction. Farm pigs (30-35 kg, n=23) were imposed in a clinically relevant model of thrombosis. We used both the common carotid arteries (CA) and the left anterior descending artery (LAD) below the first diagonal. The vessels were initially externally injured (application of pressure by forceps) followed by an appropriate for the vessel dose of thrombin (100 IU for the LAD and 190 IU for CA). Occluding thrombi was achieved in 80% for the LAD and 57% for the CA. Ten minutes post occlusion the animals were allocated under continuous electrocardiogram and ultrasonic flow meter monitoring to one of the following groups: Group A) half-dose tenecteplase (2000 IU); Group B) Full dose tenecteplase (5000 IU); Group C) saline only. All animals received 60IU heparin and antiplatelet agents. The follow-up was 120 minutes post therapy administration. Sixty minutes after lytic drug administration recanalization occurred in 58% of the occluded arteries in Group A, in 85% in Group B and in 20% in Group C (P=0.028). Both tenecteplase regimens were effective for treating carotid artery thrombosis (71% Group A vs. 75% in Group B vs. 33% in Group C, P=0.286), but low dose was significantly less effective in reestablishing flow in proximally occluded LADs (25 % in Group A vs. 100% in Group B vs. 0% in Group C, P=0.015). All vessels with restored flow at 60 minutes remained patent at least for 1 hr. In Group A, at 60 minutes after tenecteplase administration, flow velocity in LAD reached 30% of the baseline value and 45% in carotids, while in Group B flow was 160% and 55% respectively, suggesting restoration of larger lumen diameter in the treated vessels. Post reperfusion ventricular arrhythmias that required treatment occurred equally in all groups. No differences in hemodynamic tested parameters were observed between the groups. In conclusion, we developed a clinically relevant model useful for testing the efficacy of different thrombolytic regimens. Our data demonstrate that low dose tenecteplase can be successfully used for treating thrombosis of larger diameter vessels, such as the carotids, but appears inadequate for treating LAD thrombotic occlusions.

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Section: Discussionmentioning

confidence: 99%

Low dose tenecteplase restores vessel patency in a clinically relevant porcine animal model

Tseliou¹,

Ntalianis²,

Diakos³

et al. 2016

J Transl Sci

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“…We hypothesized that the presence of SUTI and/or advanced age would negatively impact the stroke rehabilitation hospital course, and ultimately decrease the likelihood of community discharge. The primary dependent variable was post-inpatient rehabilitation discharge disposition, which served as the proxy for functional status [2,16].…”

Section: Methodsmentioning

confidence: 99%

“…The primary outcome of acute thrombolysis trials has focused on a clinical endpoint of ninety day mRS (modified Rankin Scale) value [16]. However, patients and their families are interested in the events that occur during those three months that lead to the end result, namely, the process of rehabilitation care.…”

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confidence: 99%

Acute Intravenous Tissue Plasminogen Activator Therapy does not Impact Community Discharge after Inpatient Rehabilitation

Vahidy

Aramburo-Maldonado

Cai

et al. 2015

Int J Neurorehabilitation Eng

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IntroductionCerebrovascular disease is the leading cause of disability in the United States, costing an estimated $36.5 billion annually [1]. To curb cost and decrease disability rates, iterations of outcomes research are of critical importance, particularly related to post-acute rehabilitation care. In 1995, the NINDS [National Institute of Neurologic Disorders and Stroke] and Stroke t-PA (tissue plasminogen activator) trial showed improved functional outcomes at three months in patients treated with t-PA compared to placebo [2]. However, the impact of t-PA on the rehabilitation process and acute care re-hospitalization during those three months has not been elucidated.Early efforts to quantify the impact of intravenous thrombolysis on the need for inpatient rehabilitation in the acute stroke setting have been promising. In a 2011 study, acute stroke patients who received t-PA were found to have significant improvement in their NIHSS [National Institutes of Health Stroke Scale] values and increased likelihood of community discharge without an inpatient rehabilitation stay [3]. Unfortunately for the acute stroke patient who requires inpatient rehabilitation, the impact of intravenous thrombolysis on NIHSS score and eventual community discharge is unknown. AbstractBackground and purpose: Discharge status and acute re-hospitalization are used as indicators of stroke severity and recovery. Intravenous t-PA (tissue plasminogen activator) is one of two treatments shown to have a positive impact. Stroke rehabilitation patients are an important population who will end up integrated back into the community, institutionalized or hospitalized due to late stroke complications. We sought to determine factors contributing to post rehabilitation discharge and acute re-hospitalization, in particular, the impact of t-PA therapy.Methods: Retrospective analysis of census data from ischemic stroke patients on the UTHealth Stroke/ Neurorehabilitation Services at Memorial Hermann Hospital -Texas Medical Center between Jan 2011 and Nov 2013, discharged to the Community, SNF (Skilled Nursing Facility) or AC (Acute Care). Demographics and NIHSS (National Institutes of Health Stroke Scale) were collected. Discharge FIM (Functional Independence Measure) was the reference standard. Genitourinary infections were a negative mediator in the multivariate regression.Results: Of 346 patients, 274 returned to the community, 47 to SNF, and 25 to AC.NIHSS and t-PA therapy: Median NIHSS values were 8 in the community group, 11 in SNF and 9.5 in AC.31.8% of patients received IV t-PA in the community group, 23.4% in SNF and 24% in AC. There were no statistically differences in community discharge rates.Community vs. AC: One day increase in rehabilitation hospitalization correlated with 19% decreased odds of AC readmission (OR 0.81; P=0.001).One unit discharge FIM increase correlated with 13% decreased odds of AC readmission (OR 0.87; P=0.003).Community vs. SNF: One year age increase correlated with 4% increased odds of SNF admission (OR 1.04; P=0.02)...

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“…With the introduction of intravenous thrombolytic therapy and availability of modern neuroimaging modalities, timely diagnosis of an ischemic lesion and determining its vascular location and extent has led to efficient management of acute ischemic stroke and improved stroke outcomes (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%