American Heart Association

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Mechanical thrombectomy for stroke is cost-effective, but scalability remains an issue.

Neal S. Parikh, MD

Ganesalingam J, Pizzo E, Morris S, Sunderland T, Ames D, and Lobotesis K. Cost-Utility Analysis of Mechanical Thrombectomy Using Stent Retrievers in Acute Ischemic Stroke. Stroke. 2015

Five large, randomized clinical trials recently demonstrated that mechanical thrombectomy (MT) significantly reduces disability and mortality in patients presenting with proximal large vessel occlusions. MT is performed after IV-tPA administration or, when IV-tPA is contraindicated, as the sole intervention. In this issue of Stroke, Ganesalingam and colleagues seek to determine whether adjunctive MT for stroke is cost-effective, as compared to IV-tPA alone.

Data from the MT trials were used to determine the proportion of patients expected to achieve three functional categories (independent, dependent and deceased). These data were then run through a long-run Markov state-transition model to estimate the costs and outcomes over 20 years. The Markov model was transformed every 3 months over 20 years, which means patients in the independent (mRS 0,1,2) category were given the ability to have a recurrent stroke and change to any of the three states. The model utilizes cost data from the United Kingdom’s National Health Services (NHS): the cost of TPA was $2,953, the cost of MT was $13,803. The model makes a reasonable, evidence-based assumption that functional outcome correlates with quality adjusted life years (QALYs). Cost effectiveness was determined by assessing the incremental cost per gained QALY and the Net Monetary Benefits (NMB) of adjunctive MT over IV-tPA alone. NHS thresholds for willingness to pay per QALY were utilized: $33,000-$49,500.

The incremental cost of MT over IV-tPA alone was $11,651 per QALY gained. The NMB was below even the lower willingness to pay thresholds. Varying the cost of MT up to $33,000 and the utility of functional independence did not negate the results.

Given the meaningful clinical impact of MT on disability and death and the cost-effectiveness of the therapy, it is imperative that the treatment be made available to more patients. The therapy will become more cost-effective with improvements in stroke referral networks, technology and futile inter-hospital transfer rates (1). However, propagation of MT will face costly infrastructure challenges, as, even under optimal modeling, access to comprehensive stroke centers is limited in the United States (2). It would be worthwhile to assess the comparative and cost effectiveness of directed stroke prevention as compared to stroke treatment infrastructure development.

(1) Fuentes, et al. Futile interhospital transfer for endovascular treatment in acute ischemic stroke. Stroke. 2015;46:2156-2161.
(2) Mullen, et al. Optimization modeling to maximize population access to comprehensive stroke centers. Neurology. 2015;84:1196-1205.

Practice Kind of Makes Perfect

Ali Saad, MD

Strbian D, Ahmed N, Wahlgren N, Lees KR, Toni D, Roffe C, et al. Trends in Door-to-Thrombolysis Time in the Safe Implementation of Stroke Thrombolysis Registry: Effect of Center Volume and Duration of Registry Membership. Stroke. 2015

It seems intuitive that the longer you do a certain process and the more you see of a disease, the better you get at it.

This study looked at 44,359 patients in the SITS (safe implementation of stroke thrombolysis) registry in Europe from 2002-2011 and questioned whether the year a center joined the registry and the number of patients seen per year correlated with DTN (door to needle time). Mean DTN was 73 min overall. Centers that joined in 2003-2005 had a mean DTN of 68min while those who joined in 2006-2009 had a mean DTN of 72 min. Centers that saw >100 patients also had improved times and this variable actually had a more robust effect than the year the center joined the registry. Centers treating 75-100 patients per year who joined SITS early experienced a drop from 50 minutes in 2003 to 30 minutes in 2008. Although the results are significant, the only centers that saw robust drops in mean DTN were the minority that saw a large number of patients. 

Limitations of the study include not being able to perform a subgroup analysis of type of stroke center (primary, secondary, tertiary). Only 5 centers saw 100 or more patients per year. The year a center joined the SITS registry may not necessarily correlate with the experience of a center as they may very well have been practicing for years before officially joining. Outcome measures and safety data were also not mentioned. The study is biased in that centers had to opt into the registry on a voluntary basis.

How does this paper change my practice? If i had a stroke in Europe, I MIGHT (but not necessarily) go to the largest stroke center even it’s a few minutes further away than a smaller one that’s close.

Subclinical infarction post cardiac surgery: What’s the damage?

The disability that results from acute infarction is easier to recognize and treat when the patient presents with clear physical sequela of stroke. The impact of subclinical infarction is an understudied area and thus the treating physician lacks clear guidance. Neurologists are all too familiar with ordering head imaging and discovering evidence of prior ischemic insult with the patient denying history of an acute event. What is the physician to do with this information? As our population ages, one can expect that this will become a more common occurrence. More procedures, such as cardiac surgery are also being performed in the latter years. This provides an excellent backdrop upon which to investigate the sequela of accumulating new subclinical infarcts post procedure in those with pre-existing cerebrovascular disease. 

Patel et al. used rapidly evolving technology, the 3T MRI, to assess for new lesions following cardiac surgery, quantified against levels of pre-existing cerebrovascular disease, and also compared neuropsychological testing conducted at identical time intervals. Patients undergoing either a CABG and/or valve surgery at the University of Leicester were eligible for inclusion. Only those who had contraindication to MRI or were not native English speakers were excluded. 3mm 3T MRI images were obtained at intervals 1-2 weeks prior to surgery as well as 6-8 weeks postoperatively. Neuropsychological evaluation with standard battery assessments occurred at the same time intervals. Acute or chronic ischemic change was determined by comparing the DWI and FLAIR sequences by a blinded neuroradiologist. Chronic ischemic change was characterized using a computer program which looked at location and volume of the lesions. Patient cognitive improvement or decline was indicated by a change in the Z score which incorporated the mean and standard deviation from a healthy population.

77 of the 103 patients enrolled successfully completed pre/post-operative MRI and cognitive assessments. FLAIR signal change was found in 49 patients pre procedure. New FLAIR lesions were identified in 24 patients (9 with >1) post procedure with the majority occurring in the MCA territory. There were no baseline characteristics that differed between those with new lesions after cardiac surgery and those without. 22/24 with new lesions had evidence of prior FLAIR signal change. Volume comparison suggested that the accumulation of lesions following surgery is relatively minor (0.004%) in comparison with pre-existing burden (0.1%) due to chronic cerebrovascular disease. Of the 35 patients who showed a decline >1SD in neuropsychological testing following surgery, the majority (24) had NO NEW postoperative lesions. The incidence of cognitive decline (46%) was therefore irrespective of presence, number or size of new lesions. 5 patients notably had acute perioperative stroke but only one patient showed decline in cognition following the procedure.

What conclusions is the practicing neurologist to draw? The good news is that lesions accumulated post cardiac procedure found on imaging appears to have no impact on a patient’s cognition. However, the authors show that patients with pre-existing lesions were ten times more likely to experience new lesions post-operatively. While we may not fully understand the impact of these subclinical lesions, it does confirm what we know to be true. There must be something about the patient population with silent ischemic disease that predisposes them to further insult making prevention all the more important.

DVT Prophylaxis after ICH: What do YOU do?!

Mark N. Rubin, MD

Prabhakaran S, Herbers P, Khoury J, Adeoye O, Khatri P, Ferioli S, and Kleindorfer DO. Is Prophylactic Anticoagulation for Deep Venous Thrombosis Common PracticeAfter Intracerebral Hemorrhage? Stroke. 2015

Intracerebral hemorrhage (ICH), as has been discussed and re-discussed, is not only a terrible neurologic illness with exceedingly high morbidity and mortality, but systemically trying as well. Among the myriad complications that arise in the early period after ICH, venous thromboembolism (VTE) is perhaps chief among them given the potential morbidity and mortality, with one study suggesting a nearly four-fold increase in incidence as compared to ischemic strokes (1.9% vs 0.5%). This makes for an ostensibly difficult clinical conundrum, given the appropriate reluctance to anticoagulate – the preferred means of VTE prophylaxis – in the setting of ICH. However, given the suggestion that most ICH hematoma growth is in the first 24-48 hours from ictus, there is a guideline-based recommendation (albeit with a low level of evidence supporting it) to initiate low-dose heparin or heparinoid once a patient is 24-96 hours from the event and there has been demonstration of cessation of bleeding. Given the clinical dilemma of anticoagulating in the setting of a hemorrhage and the lack of high-level evidence to guide therapy, the current investigators conducted a nationwide survey to ascertain a gestalt of pharmacologic VTE prophylaxis in this country in the setting of ICH.

The survey was conducted in a standardized and structured fashion via an ICD-9-code-based database that includes all payer types (to expand the generalizability past, say, the Medicare population only), screening for adult ICH patients from 2006-2010. They found 32,690 patients meeting their inclusion criteria and, based on pharmacy records, only 5,395 (16.5%) received any prophylactic anticoagulation during the hospital stay. Among these patients, 2,416 (44.8%) received a dose by hospital day 2 and the dominating agent was unfractionated heparin (71.1% of those patients). Of interest, there was a trend toward increasing use of VTE prophylaxis over the study period (14.3% to 18% of patients) and there was a large variation in use by region, with the Northeast leading the way with 23.2%, the South 19%, the Midwest 10.8% and the West 9.8% of patients. Geographic location was the only independent predictor of prophylactic anticoagulation in their study.

This study has interesting implications not only for ICH practice but guideline-based initiatives for any clinical situation. Why are less than 20% of patients receiving what should be a safe intervention to prevent a major, life-ending complication? Is it only because some practitioners cannot get past the use of anticoagulants in the setting of a hemorrhage, in spite of an (albeit lacking) evidence-base and guideline to support the practice? Are these data and guidelines broadly accessible? Should this practice be under the kind of scrutiny we all know of when we care for other types of stroke (acute ischemic stroke in particular)? How does batting 0.200 compare to other guideline-based recommendations in acute neurology? Or any other specialty?

Acute Stroke Care in Europe

Ali Saad, MD

Wiedmann S, Hillmann S, Abilleira S, Dennis M, Hermanek P, Niewada M, et al. Variations in Acute Hospital Stroke Care and Factors Influencing Adherence to Quality Indicators in 6 European Audits. Stroke. 2015

This is a European study looking at risk factors that impact variations in acute hospital stroke care during 2007-2008. The authors used national databases from Germany, Poland, Scotland, Catalonia, Sweden, England/Wales/Northern-Ireland to look at demographic and clinical characteristics.

Key findings were that older patients were less likely to get thrombolysis, anticoagulation, and stroke unit care, but were more likely to be screened for dysphagia. Women were also less likely to receive anticoagulation/antiplatelet treatment or stroke unit treatment. aside from these trends, the study also found that there was great variation in stroke quality indicators like the delivery of thrombolytics, dysphagia screening, admission to a stroke unit for care, anticoagulant therapy, antiplatelet therapy etc. The use of thrombolytics alone varied from 1.3% to 9.1% among different audits.

Standardizing care in Europe would be more difficult compared to the US given hospitals’ different definitions of a stroke unit and the lack of a unifying governing body. Although the EU helps provide universal health care, it currently does not dictate best clinical practice for stroke. Joint Commission International does accredit hospitals as primary stroke centers, but no European countries have participated in this accreditation. I contacted the European stroke organization with the same question and am waiting to hear back from them. i’ll update this blog post with a comment if I do.

Some similarities the authors found compared to the US data include older patients being less likely to receive anticoagulation for Afib and more likely to receive dysphagia evals.

For those interested in the “weekend effect” on the delivery of stroke care, this study did not find one. the literature shows no consistent weekend effect and varies widely by country and hospital studied. Even different studies done of the same country, but at different hospitals or periods of time, show inconsistent findings.

Limitations of this study include no mention of a body (or lack thereof) that accredits stroke cares or enforces standard of care through hospital reimbursement like in the US. It is a retrospective study of several European countries so selection bias may have occurred. Although the authors showed a variation in stroke care, they did not present numbers comparing the same parameters measured in US counterparts, the data was also too limited to provide measures like functional outcome and mortality to show whether the lack of standardized care translated to worse morbidity and mortality. Lastly, there is no mention of a key stroke quality measure, post-stroke rehab, possibly due to the lack of data.

How does this study change my practice? It makes me more cognizant of biased treatment of women and the elderly. also makes me aware of the lack of standardized care for acute stroke in Europe.

Long term annual cost of ischemic stroke and intracranial hemorrahge

Duy Le, MD

Previous attempts have been made to evaluate the economic burden of ischemic stroke. The NEMESIS study, an Australian based study, evaluated costs 3 to 5 years out from the original stroke event. Gloede et al push the envelope by attempting to quantify the cost of ischemic stroke (IS) and intracranial hemorrhage (ICH) 10 years out. They used The Model of Resource Utilization Costs and Outcomes for Stroke (MORUCS) which was also employed by the NEMESIS study. NEMESIS patients were evaluated in this study and followed out to 10 years. The cost of illness models for both IS and ICH were updated from a 2004 to 2010 reference year, adjusting for inflation. The Australian population was used in this model and currency translated to USD in terms of cost.  

For first ever IS, 243/283 of the NEMESIS participants were interviewed (86% responder rate). For first ever ICH, 43/50 of the NEMESIS participants were interviewed. For IS, the overall average annual direct cost at 10 years was similar to survivors between 3-5 years (5,207 USD). The distribution of the costs however varied, as medication increased from 13% to 20%, while cost for rehabilitation services and facilities decreased over that same time span. ICH on the other hand had an increase of 24% in annual direct costs (from  5,807 USD to 7,607). Aged-care facility-costs for ICH were noted to be 64% higher at 10 years compared to 3-5 years. Costs were highest within the first year for both IS and ICH. Although the most practical way to evaluate the question of long term cost is to employ surveys as this study did; this is also the study’s biggest limitation. Surveys inherently can be biased, depending on the responder. Additionally, an Australian population was analyzed in an attempt to extrapolate costs for US patients. 

From this study, we find out that the cost of a first time ischemic stroke goes beyond the initial costs up front. The annual cost 10 years post IS however are not different from 3-5 years post IS. While some may argue this does not offer much information to us, it still reaffirms the fact that the financial burden of stroke is felt long after in the initial event. On the other end, ICH costs increase annually at 10 years compared to 3-5 years due to increased care facility costs; further making the point that the financial burden of these disease processes continue long after the index event.  Patient, families and physicians should be aware of this when dealing with patients in both the inpatient and outpatient setting with these disease processes.

A Familiar Stroke Prognosis Model Finds External Validation

Ali Saad, MD

Bray BD, Campbell J, Cloud GC, Hoffman A, James M, Tyrrell PJ, et al. Derivation and External Validation of a Case Mix Model for the Standardized Reporting of 30-Day Stroke Mortality Rates. Stroke. 2014

Prognosis can be a trepidacious component of the post-stroke conversation. Practitioners are often hesitant to provide concrete answers to patients and their families, leading to frustration on both sides. Multiple stroke prognosis scores have been created over the years and focus on NIHSS, age, and non-lacunar sub-type as the main variables. These scores are limited by lack of external validity, use of variables not universally recorded in the stroke registry, and limitation of use for either ischemic or hemorrhagic stroke.

This British study demonstrates external validity of a model that uses these common variables to predict 30 day ischemic/hemorrhagic stroke mortality. Internal data was derived from the Sentinel Stroke National Audit Programme (January-June 2013) and external validation was done using the South London Stroke Register (2005-2012).

2 models were ultimately created, A and B. The variables used were:
age (<60, 60-69, 70-79, 80-89, 90 or greater), Afib, ischemic or hemorrhagic stroke subtype, and NIHSS. The 2 models differed in that A used the full NIHSS while B used only the level of consciousness component.

Model A had a c-statistic of 0.86 (95% CI 0.85-0.88) and 0.87 (0.84-0.89) for internal and external validation respectively. For Model B, the corresponding c-statistics were 0.82 (0.81-0.83) and 0.86 (0.83-0.89)

The disadvantage of this model is that its c-statistic predictive value is not significantly better than prior models, like the iScore. Other limitations include this model being internally and externally validated in a UK (albeit ethnically diverse) population. It is also unknown whether these patients received IV-tPA, clot extraction, or aggressive measures for their bleeds, all of which would certainly skew outcomes.

The advantage of this model is that it only uses a few key variables and may be used for ischemic or hemorrhagic stroke. NIHSS’s are often incomplete in the medical record and level of consciousness alone appears to be a good surrogate. The population from the Sentinel program was unselected thereby making it more robust. Future stroke studies may now consider this model given its external validation and permission of cases mixing.

Cracking ICD-9-CM Codes: Accuracy of Discharge Diagnoses in Stroke

Mark McAllister, MD

Jones SA, Gottesman RF, Shahar E, Wruck L, Rosamond WD. Validity of Hospital Discharge Diagnosis Codes for Stroke: The Atherosclerosis Risk in Communities Study. Stroke. 2014

Epidemiological estimates regarding stroke prevalence and mortality are often based on ICD-9-CM codes from hospital discharge. The accuracy of such statements is dependent on the codes actually corresponding to the labelled diagnosis. The authors sought to investigate the sensitivity and positive predictive values of ICD-9-CM codes for stroke and intracranial hemorrhage using diagnoses from the Atherosclerosis Risk in Communities (ARIC) study as the gold standard.

The ARIC study is comprised of nearly 16,000 patients in four communities in the US, and the database was searched for hospitalizations for ischemic strokes and intracranial hemorrhage. Strokes were identified by use of a stroke/hemorrhage related ICD-9-CM code, keywords in the discharge summary, or cerebral radiographic findings and validated by both computer algorithm and physician reviewer. Using this group of validated stroke and hemorrhage diagnoses the ICD-9-CM codes were compared.

Looking at AHA/ASA code groupings for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage they found the positive predictive value to be 76% and sensitivity of 68%. An alternative grouping using more ICD codes increased sensitivity to 83%. These numbers are lower than previously published values and suggest stroke incidence may be underestimated based on ICD-9-CM codes.

10 years of experience with telestroke in Germany

Ali Saad, MD

Müller-Barna P, Hubert GJ, Boy S, Bogdahn U, Wiedmann S, Heuschmann PU, and Audebert HJ. TeleStroke Units Serving as a Model of Care in Rural Areas: 10-Year Experience of the TeleMedical Project for Integrative Stroke Care. Stroke. 2014

This paper presents data from the German telestroke network, TEMPiS (TeleMedical Project for integrative Stroke Care). Established in 2003, it provides remote stroke expertise to rural areas in Germany. They used prospective registries from TEMPiS hospitals from 2003-12 and looked at typical stroke metrics.

Key findings were
– percentage of patients seen in the hospital with stroke/TIA as the diagnosis 19%->78%
– thrombolytic administration 2.6%->15.5%,
– median onset to treatment time 150min->120min
– door to needle time 80min->40min

Limitations of the TEMPiS experience include the lack of data on sustainability due to its novelty. The data excludes in-hospital strokes, but included hemorrhagic strokes. Included patients were from the largest insurer in the area, but it only covers 40% of the population.

This treatment model is great for rural areas without access to large stroke centers as well as patients who prefer treatment at their local hospital. It also provides evidence that although stroke centers provide excellent care, telestroke is a cost-effective solution to rural areas who may not have the local expertise needed. The TEMPiS experience echoes the success of the telestroke networks in GA, USA and Alberta, CA.

The authors highlight the need to develop relationships with the surrounding community hospitals and convince them that telestroke will provide care that is reliable and beneficial to their patients. This might seem to go without saying, but one must keep in mind that these rural hospitals have been managing without this service for years. It takes great leadership and some charisma to convince a group of doctors to change the way they’ve been practicing for years and invest in a new system.