By Michael P. Lerario, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College; Attending Physician, New York-Presbyterian Queens Hospital; and Medical Director of the New York-Presbyterian Mobile Stroke Unit
Dr. Lerario reports no financial relationships relevant to this field of study.
SYNOPSIS: Deployment of a mobile stroke treatment unit in the field results in a higher percentage of patients treated with intravenous tPA, at a shorter interval from onset of symptoms, and results in better outcomes.
SOURCE: Kunz A, Ebinger M, Geisler F, et al. Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: An observational registry study. Lancet Neurol 2016;15:1035-1043.
Clinical data have established that the benefit-to-risk ratio of intravenous (IV) thrombolysis for acute ischemic stroke progressively improves when IV tPA is administered closer to the time of stroke onset.1 The number needed to treat to obtain one favorable outcome of no disability at three months following IV thrombolysis ranges from 4.5 for treatment within 0-90 minutes, to 9.0 for 91-180 minutes, to 14.1 for 181-270 minutes.1 Even delays as small as 15 minutes have been shown to significantly worsen in-hospital mortality, increase the risk of symptomatic intracranial hemorrhage (ICH), reduce the rate of recovery to independent ambulation, and decrease the likelihood of discharge home from the hospital.2 Unfortunately, only a minority of patients receive tPA within 90 minutes of stroke onset,3 or even within 60 minutes of arrival to the emergency department.4 This has resulted in the development of systematic approaches aimed to reduce in-hospital door-to-needle times.5 However, such approaches do not address prehospital delays, which have been shown to be the largest contributor to delays in tPA administration.6
Recently, a German team of physicians published their experience with prehospital IV thrombolysis for acute stroke patients. They equipped a specialized ambulance with an on-board computed tomography scanner and point-of-care laboratory testing. These mobile stroke units (MSUs) are staffed with a neurologist, a paramedic, and a radiology technician and are dispatched to the scene when a patient’s emergency call raises the clinical suspicion for stroke. Such units are capable of bringing standard-of-care stroke diagnostics and treatments directly to the patient’s doorstep, effectively removing unnecessary delays associated with transport times and hospital handoffs. In PHANTOM-S, the first randomized MSU trial, Ebinger et al reported a median reduction of 25 minutes in the time to treatment from stroke alarm, when compared to the routine transport of stroke patients.7 Thrombolysis rates were higher for stroke patients treated on the MSU, and the proportion of patients treated within the first hour following stroke onset (i.e., “the golden hour”) was six-fold higher with MSU deployment. Although an effect on the time to treatment was clearly demonstrated in this study, PHANTOM-S was not powered to detect a clinical benefit.
In a recent issue in Lancet Neurology, Kunz et al assessed the effect of MSU treatment on three-month disability outcomes using a prospective registry. Patients included in the registry were taken from the PHANTOM-S trial and its pilot phase, as well as an ad-hoc, nonrandomized continuation of the study based on a sample size calculation performed following the completion of the PHANTOM-S trial. The analysis was restricted to patients admitted to hospitals within the MSU catchment area and who were transported either by the MSU or by primary emergency medical services as a control arm. Patients were required to have a known time of stroke onset within 4.5 hours for this study. To better assess disability outcomes, the primary study population was restricted to patients who had lived at home without assistance before the index event. Follow-up for outcome assessment was assessed at three months by a standardized telephone interview, mail-in questionnaire, or via a discharge letter in patients who died in the hospital. The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0-1 (i.e., no disability) at three months.
The registry included 305 patients in the MSU arm and 353 patients in the standard transport arm who were evaluated in the primary analysis. Except for more women, higher blood pressure, and lower initial blood glucose values in the MSU group, the baseline parameters were well-balanced. In this study, the mean onset-to-treatment time was 33 minutes shorter (96.3 vs. 129.3; P < 0.0005) for patients receiving care in the MSU. Significantly more patients in the MSU arm received tPA within 60 minutes (37% vs. 4%; P < 0.0005) and 90 minutes (62% vs. 35%; P < 0.0005) of onset. In the primary outcome (mRS 0-1 at three months), there was no significant difference between treatment groups (53% in the MSU arm vs. 47% with conventional care; P = 0.14). However, multiple secondary outcomes clearly demonstrated the potential for benefit with MSU care. The dichotomized secondary outcomes of mRS score 0-3 (i.e., survival without severe disability; 83% vs. 74%; P = 0.004) and mortality (6% vs. 10%; P = 0.22) were more favorable for patients treated on the MSU. After adjusting for stroke severity and other covariables, there was a trend for higher rates of survival without disability in patients treated on board the MSU, with an odds ratio of 1.40 (95% confidence interval, 1.00-1.97; P = 0.052). Ordinal regression analysis resulted in a significantly better outcome for patients in the MSU cohort over the full range of the mRS. Safety outcomes did not differ between patients in the two arms, for either symptomatic ICH (P = 0.27) or seven-day mortality (P = 0.23).
This study further demonstrates the time benefit of a novel prehospital treatment approach for stroke patients, with MSU care allowing tPA administration approximately 30 minutes earlier than compared with standard transport. When taken together, these results describe the potential of MSU care to benefit acute ischemic stroke patients by significantly reducing severe disability and death at three months with similar rates of hemorrhage. This study was mainly limited by its nonrandomized design and by nonblinded outcome assessments, which were performed by different raters in the two study arms. Although studies such as this one are promising, further trials are necessary to prove that MSU care is an effective and cost-saving approach to shortening tPA treatment times and improving disability outcomes in stroke patients. Experience with stroke ambulances in the United States has been increasing as well, and a multisite, randomized trial is currently enrolling to more precisely establish the benefit of prehospital thrombolysis.8
- Lees KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome in stroke: An updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010;375:1695-1703.
- Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013;309:2480-2488.
- Wahlgren N, Ahmed N, Dávalos A, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): An observational study. Lancet 2008;372:1303-1309.
- Fonarow GC, Smith EE, Saver JL, et al. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: Patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation 2011;123:750-758.
- Ruff IM, Ali SF, Goldstein JN, et al. Improving door-to-needle times: A single center validation of the target stroke hypothesis. Stroke 2014;45:504-508.
- Evenson KR, Foraker RE, Morris DL, Rosamond WD. A comprehensive review of prehospital and in-hospital delay times in acute stroke care. Int J Stroke 2009;4:187-199.
- Ebinger M, Kunz A, Wendt M, et al. Effects of golden hour thrombolysis: A Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke (PHANTOM-S) substudy. JAMA Neurol 2015;72:25-30.
- Bowry R, Parker S, Rajan SS, et al. Benefits of Stroke Treatment Using a Mobile Stroke Unit Compared With Standard Management: The BEST-MSU Study Run-In Phase. Stroke 2015;46:3370-3374.