Category: Stroke

For tPA, Is Delusion the Standard of Care?

Yet again, the tPA apologists dip into their bag of registry data in an attempt to defend tPA – and end up contradicting themselves.

In 2009, neurologists in India published a retrospective case series examining the outcomes following tPA at their institution.  Specifically, they divided up the cases between those with arterial occlusion present on CT angiogram of the cerebral vessels, and those with no demonstrated arterial occlusion.  For patients with demonstrated occlusion, there were significant differences in early NIHSS improvement favoring tPA, but no long term mRS improvements.  Conversely, there were 119 without occlusion present – and the early NIHSS improvement and late mRS improvement outcomes were similar.  There were, however, substantial baseline differences between those receiving tPA and those who did not – and retrospective studies are confounded by many biases – but there was at least a suggestion that some stroke subtypes might not benefit from tPA.

Clearly, that did not sit well with the authors of this study, a handful of whom are paid representatives of Boehringer Ingelheim.  They performed their own retrospective review of a multi-center registry to evaluate outcomes of patients without arterial occlusion demonstrated on initial angiography, but definitive acute stroke seen on follow-up MRI.  They also further subdivided stroke subtypes into lacunar (subcortical, thalamic, and pontine infarct <20mm) vs. non-lacunar (all others).

They identified 154 non-lacunar strokes, 49 of whom underwent thrombolysis, and 102 lacunar strokes, 54 of whom underwent thrombolysis.  Outcomes favored tPA for non-lacunar stroke syndromes, with 51% of tPA patients mRS 0-1 at 90 days, compared with 30% for those who did not receive tPA.  Symptomatic intracranial hemorrhage occurred in 6.1% of tPA patients, compared with 1% without.  Lacunar strokes, however, had identical 90 day mRS outcomes – 65% vs. 63%.  For lacunar strokes, sICH occured in 3.7% of tPA patients vs. 0% without.  The authors still try to statistically adjust their way out of this equivalency for the primary outcome – but fail.

So, again, this is a retrospective study confounded by many biases.  However, the authors have nicely demonstrated support for a hypothesis some stroke subtypes – particularly those for whom no arterial occlusion is demonstrated on angiography – might not benefit from tPA.  Thus, the conclusion:

“In conclusion, this retrospective study demonstrates the efficacy of intravenous thrombolysis in patients with ischemic stroke who have no radiographically demonstrated arterial occlusion at presentation. Both subgroups, nonlacunar and lacunar strokes, were found to have had better clinical outcome after receiving r-tPA.”

Or, the opposite of what their data suggests.

Is it really so impossible conceive tPA might not be magical?

“Thrombolysis in Ischemic Stroke Without Arterial Occlusion at Presentation”

Should the 48-hour Cardioversion Window Be Revised?

It has become generally accepted practice to treat new-onset atrial fibrillation and atrial flutter with electrical cardioversion in the acute setting – provided the known onset of atrial fibrillation is less than 48 hours.  Beyond that, caution tends to be advised – whether through use of transesophageal echocardiography to rule out left atrial thrombus, or through pre- and post-procedural anticoagulation.

However, this data from a research letter in JAMA suggests – possibly we ought to be even more cautious regarding time-of-onset.

This is a re-analysis of FinCV, a 7 year trial registry of cardioversion for atrial fibrillation from Finland.  The study cohort is comprised of 2,481 patients undergoing 5,116 electrical cardioversions, all without peri-procedural anticoagulation for symptom onset <48 hours.  Outcomes were gathered from vital records review, evaluating for cerebrovascular thrombotic complications within 30 days.

Of these patients undergoing cardioversion, there were 38 definite thrombotic complications.  30 of these 38 occurred in patients whose symptom onset was >12 hours.  There were few apparent pro-thrombotic differences between groups, and thus, the authors very reasonably conclude – we should be cautious regarding cardioversion after 12 hours.  Other predisposing factors in their multivariate analysis include female sex, heart failure, and diabetes – but increasing length of time showed the strongest association.

The 12-48 hour window in this study still only represented a 1.1% risk for 30-day thromboembolism, compared to the ~2% risk after 48 hours.  However, it still exceeds the ~0.3% risk of thromboembolism with peri-procedural anticoagulation.  There are other risks associated with anticoagulation, but it is reasonable to suggest the management strategy is no longer as clear-cut around 48 hours.

“Time to Cardioversion for Acute Atrial Fibrillation and Thromboembolic Complications”
http://www.ncbi.nlm.nih.gov/pubmed/25117135

Just Another Advertisement for tPA

As with last week’s coverage of the updated Cochrane Systematic Review for tPA in acute ischemic stroke, the key question is: what’s new?

The first pooled meta-analysis, published in The Lancet in 2004, included NINDS, ECASS I, ECASS II, and ATLANTIS.  It was subsequently updated in 2010 to add ECASS III and EPITHET.  Now, these authors have decided to add IST-3.

I am actually a huge fan of individual-patient meta-analyses.  Depending on the data availability, the similarity of trial protocols, and other issues associated with heterogeneity, this is the gold-standard for aggregating data and increasing power.  Individual-patient analyses also allow for more reliable exploration of subgroup effects not otherwise possible through regular meta-analyses or systematic reviews.

But, at the crux of it, a meta-analysis is only as good as the included trials – and this is a topic much debated over the last twenty years.  Entertainingly, the 2014 publication includes this bland statement:

Role of the funding source 

The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data and responsibility for the decision to submit for publication.

Yes, the funding source had nothing to do with the study design, excepting all the folks receiving speaker fees and honoraria – and the fact the original idea and refinements to the approach were contributed by one of the authors who is an employee Boehringer Ingelheim:

KRL has received speaker fees from and has served on the data monitoring committee of trials for Boehringer Ingelheim; his department has received research grant support from Genentech.  GA has received research grant support from Lundbeck, fees for consultancy and advisory board membership from Lundbeck, Covidien, Codman, and Genentech, fees for acting as an expert witness, and owns stock in iSchemaView. EB is employed by Boehringer Ingelheim. SD has received honoraria from Boehringer Ingelheim, EVER Pharma, and Sanofi and has received fees for consultancy and advisory board membership from Boehringer Ingelheim and Sanofi. GD has received research grant support from the NHMRC (Australia) and honoraria from Pfizer and Bristol-Myers Squibb. JG has received fees for consultancy and advisory board membership from Lundbeck. RvK has received speaker fees and honoraria from Penumbra and Lundbeck. RIL has received honoraria from Boehringer Ingelheim. JMO has received speaker fees from Boehringer Ingelheim. MP has received travel support from Boehringer Ingelheim. BT has received honoraria from Pfizer.  DT has received speaker fees and fees for consultancy and advisory board membership from Boehringer Ingelheim and Bayer.  JW has received research grant support from the UK Medical Research Council and from Boehringer Ingelheim to the University of Edinburgh for a research scanner bought more than 10 years ago. WW has received research grant support from the UK Medical Research Council. PS has received honoraria for lectures which were paid to the department from Boehringer Ingelheim. KT has received research grant support from the Ministry of Health, Labour, and Welfare of Japan, and speaker fees from Mitsubishi Tanabe Pharma.  WH has received research grant support from Boehringer Ingelheim, and speaker fees and fees for consultancy and advisory board membership from Boehringer Ingelheim.

The same level of COI was present in previous versions – including employees of the sponsor as authors – but, interestingly, at least the 2004 version explicitly acknowledges a critical issue:

Role of the funding source 

For the ATLANTIS trials, Genentech provided full support for the study and Genentech employees participated to some extent in study design, data collection, data analysis, and data interpretation, writing of the report, and in the decision to submit the manuscript for publication. For the ECASS trials, Boehringer Ingelheim provided full support. Employees of Boehringer Ingelheim participated in study design, in data collection, data analysis, data interpretation, writing of the report, and in the decision to submit the report for publication.

Nothing has changed.  If you trusted the data then, you trust the data now – and vice-versa.

So, what is new?  If anything, what’s new is worse than preceded it.  The authors have nearly doubled the cohort for analysis – by the inclusion of a decade-long trial crippled by the bias introduced by an open-label, mostly unblinded design.  Despite the massive resources invested in conducting it, unfortunately, IST-3 is too flawed for inclusion – due to the unfortunate likelihood any small positive signals regarding tPA are certain to be exaggerated.  And, simply put, that’s where the astute reader ought to stop reading this publication.  There’s no point in trying to interpret their results, to fuss over the heterogeneity between trials, missing baseline characteristics for their many subgroup analysis, or whether the trials stopped early for harm or futility – ATLANTIS – are properly acknowledged.  The authors also omit several planned secondary analyses described in their statistical protocol – although, considering the garbage-in/garbage-out nature of this work, it’s of debatable importance.

The last decade of prospective research – ECASS III and IST-3 – has done nothing but degrade the quality of evidence describing tPA in acute ischemic stroke.  If there is, indeed, anyone left on the fence regarding the pro/con tPA debate, this effort ought move the needle zero to none.  Very early treatment with tPA probably benefits a properly selected subset of patients with acute ischemic stroke.  The rest – whether increasing age, high-or-low NIHSS, specific stroke syndromes, or time-dependent factors – have much smaller, if any, chance of benefit exceeding chance of harm.  Until we have unbiased evidence, we’ll never truly know how to best select patients for this therapy – and neurologists will continue to lament low treatment rates, while Emergency Physicians continue to reject pro-tPA clinical policies.  Only new, independent data has a chance to substantially change our approach to acute ischemic stroke.

“Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60584-5/abstract

The tPA Cochrane Review Takes Us For Fools

It’s been 5 years since the last Cochrane Review synthesizing the evidence regarding tPA in acute ischemic stroke.  Clearly, given such a time span, in an area of active clinical controversy, a great deal of new, important, randomized evidence has been generated!

Or, sadly, the only new evidence available to inform practice is IST-3 – a study failing to demonstrate benefit, despite its pro-tPA flaws and biases.  So, it ought not be a very exciting update, considering the 2009 version included 26 trials, and the 2014 update now includes only 27 trials.  Their summary conclusion, with only additional evidence of regression to the mean, ought remain essentially the same, or even less optimistic, right?

Of course not:

2009:
Overall, thrombolytic therapy appears to result in a significant net reduction in the proportion of patients dead or dependent in activities of daily living. This overall benefit was apparent despite an increase both in deaths (evident at seven to 10 days and at final follow up) and in symptomatic intracranial haemorrhages. Further trials are needed to identify which patients are most likely to benefit from treatment and the environment in which thrombolysis may best be given in routine practice.

2014:
Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Those treated within the first three hours derive substantially more benefit than with later treatment. This overall benefit was apparent despite an increase in symptomatic intracranial haemorrhage, deaths at seven to 10 days, and deaths at final follow-up (except for trials testing rt-PA, which had no effect on death at final follow-up). Further trials are needed to identify the latest time window, whether people with mild stroke benefit from thrombolysis, to find ways of reducing symptomatic intracranial haemorrhage and deaths, and to identify the environment in which thrombolysis may best be given in routine practice. 

They added a neutral trial comprising 43% of the tPA subjects to the existing analysis, and now it can be decisively promoted “up to six hours”?  How is this conceivable?

So, in the most literal sense, technically, the authors’ statement is not untrue.  Analyses 1.12 and 1.13 aggregate all patients treated in trials between 0-6 hours, looking at mRS 0-2 and 0-1 at the end of follow up.  Indeed, for mRS 0-2, the OR favors thrombolysis at 1.17 (1.06 to 1.29), and for mRS 0-1, the OR favors thrombolysis at 1.29 (1.16 to 1.43).  Therefore, the authors are not falsely advertising tPA as beneficial for reducing death and dependency out to six hours – as long as you wear your pro-tPA blinders.

These authors, with multiple professional and financial conflicts-of-interest, simply choose to focus on inappropriate chunking of data for a theoretically time-dependent condition, rather than acknowledge their own analyses performed providing evidence to the contrary.  Analysis 1.21, in which they split out the patients treated into 0-3 and 3-6 hour cohorts, clearly demonstrates there is no basis upon which to claim benefit beyond 3 hours.  The OR for favorable outcome with thrombolysis in the 0-3 hour window is 1.53 (1.26 to 1.86), but the OR for 3-6 hours is 1.07 (0.96 to 1.20).  Then, the authors also neglect to mention Analysis 1.26, showing deaths are neutral between 0-3 hours, with an OR of 0.91 (0.73 to 1.13), but increased by thrombolysis in the 3-6 window, with an OR of 1.16 (1.00 to 1.35).

So, tPA after 3 hours: no functional outcome benefit and increased deaths – yet the authors are extolling the benefits of tPA to 6 hours?  There is no reasonable justification for such distorted reporting of their own analyses.  Simply unacceptable – and grossly misleading for the vast population of clinicians who do not or cannot access the full text, and only read the abstract.

Let’s be perfectly clear – I am not anti-tPA.  I am, however, opposed to the unfettered expansion of tPA as guideline-mandatory treatment to a larger eligible cohort – as is increasingly prevalent across contemporary literature, and fueled by manufactured-sponsored COI.  Acute ischemic stroke is a heterogenous disease, with varying underlying etiology and diverse cerebrovascular substrate.  It is clear there are subsets of patients for whom the likelihood of harm from tPA exceeds the benefit, and we ought to be using precision medicine to narrow the treatment population, not expand it.

Thanks to Rory Speigel (@EMNerd_) for alerting me to this publication.

“Thrombolysis for acute ischaemic stroke (Review)”
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000213.pub3/abstract

Lives Saved … or Profiteering by Overdiagnosis?

Following an initial acute ischemic stroke, a search for the cause must be undertaken – for small vessel vasculitis, atherosclerotic emboli, thrombi from the systemic circulation, and so forth, beyond the domain of the Emergency Physician.  However, what the Emergency Physician does encounter is the sequelae of this search, in the form of oral anticoagulants.

These two articles from the New England Journal of Medicine, on their own, seem to reflect advances in diagnostic yield following acute ischemic stroke or transient ischemic attack.  The authors point out approximately 25% of patients suffering AIS and half of those suffering TIA never receive an ultimate identified etiology for stroke – and are classified as “cryptogenic”.  The authors in each of these studies suppose this may be due to the paroxysmal nature of atrial fibrillation, and that short-term electrocardiographic monitoring is missing this diagnosis.  In each study, some type of long-term monitoring technology is utilized, and, ultimately, the rate of diagnosis for paroxysmal atrial fibrillation jumps from 1-3% in each cohort to 8-12% in each cohort.

The catch – scads of authors for each report conflict-of-interest with both manufacturers of novel oral anticoagulants, or device manufacturers likely related to continuous ambulatory monitoring.  There is clear benefit to each of these parties, considering potential expanded indication for both monitoring and for anticoagulation.  These articles will likely be used to support both activities, despite not measuring any patient-oriented benefit.  How much of a primary or recurrent stroke risk is attributable to these very-infrequent paroxysms of atrial fibrillation?  Do they benefit equally from anticoagulation?

Given the conflict-of-interest enshrined in these articles, I am certain the advertised presumption will be they do.  They may, of course, be right – or, this may turn into yet another example of overdiagnosis and high-cost, low-yield medicine.

“Atrial Fibrillation in Patients with Cryptogenic Stroke”
http://www.nejm.org/doi/full/10.1056/NEJMoa1311376

“Cryptogenic Stroke and Underlying Atrial Fibrillation”
http://www.nejm.org/doi/full/10.1056/NEJMoa1313600

How Much Money Is Wasted By Endovascular Treatment for Stroke?

If you recall, last year was a bumper crop of prospective, randomized, controlled trials testing the efficacy of endovascular devices versus tPA alone for acute ischemic stroke.  These trials – SYNTHESIS, MR-RESCUE, and IMS-III – were unified by demonstrating no additive benefit.  Of course, these trials proved nothing to proponents of endovascular therapy, owing to the “outdated” devices used.

Interestingly, IMS-III also prospectively gathered costs associated with both treatment modalities.  Presumably, the authors expected to show a treatment advantage despite increased costs, and would follow-up with a cost-effectiveness analysis.  Now, since there was no advantage with endovascular treatment, this is simply a fascinating observational report.

So, how much did everything cost?  The answer, like everything in medicine:  depends on who’s paying.  Hospital charges for patients receiving tPA were a mean of $86,880, with a median of $58,247, and ranged from $13,701 to $830,652.  Hospital charges for endovascular treatment would have been a mean of $113,185, with a median cost of $86,481, and ranged from $23,350 to $552,279.  Thankfully, this is the funny money that few patients are realistically expected to pay.  Costs, on the other hand, are based off the negotiated Medicare reimbursements, and were estimated at a mean cost of $25,630 for IV tPA and $35,130 for endovascular therapy.  So, a fair bit of extra cost to the system for a therapy that isn’t providing any proven benefit.

Given the lack of efficacy and increased costs, you’d think it should be obvious we ought not be deploying endovascular therapy widely – but, clearly, this is unfortunately not the case.  Medicare and Medicaid still reimburse for endovascular interventions – and its use is bolstered by its sponsors and other such propaganda in the NEJM.  Until proven otherwise, this is all simply money down the drain.

“Drivers of Costs Associated With Reperfusion Therapy in Acute Stroke: The Interventional Management of Stroke III Trial”
http://stroke.ahajournals.org/content/early/2014/05/13/STROKEAHA.113.003874.abstract

Stroke MRI in 6-Minutes or Your Money Back

Despite the advances of modern medicine, the non-contrast CT of the brain is a crude tool.  It is especially poor in the setting of acute stroke – infrequently providing helpful diagnostic information, while serving primarily to rule out intracranial hemorrhage.

These authors, however, offer us a glimpse of the MRI of the future – a useful diagnostic test without long delays of image acquisition time.  These authors report on a single-center, convenience sample of patients with acute neurologic deficits who were able to undergo MRI.  They use a 3.0T MRI to acquire DWI, FLAIR, GRE, perfusion, and MRA sequences using a 6-minute protocol on 62 patients, and two radiologists rated image quality as moderate or good 94% or greater for each modality.

The authors also provide two sample cases, one of which being an acutely altered, profoundly disabled patient within the 3-hour window for tPA.  The 6-minute MRI, however, showed heterogeneous perfusion abnormalities more suggestive of seizure, rather than stroke.  After treatment with anti-eplipetics, the patient made a full neurologic recovery.

This series is small enough it’s clearly just a technology pilot.  Additional study regarding diagnostic accuracy and feasbility in the acute setting is necessary, but it would certainly be a vast improvement over the current state of the art.  Considering the present rush to judgement for tPA and the likelihood of overtreatment of stroke mimics, a diagnostic modality that adds to clinical assessment is sorely needed.a

“Six-Minute Magnetic Resonance Imaging Protocol for Evaluation of Acute Ischemic Stroke: Pushing the Boundaries”
http://www.ncbi.nlm.nih.gov/pubmed/24916906

The Struggles of tPA Consent

Providing informed consent for any therapeutic intervention can be challenging.  And, then there’s stroke.  Acute stroke spans the gamut from mildly limiting to profoundly disabling – with a non-linear relationship between the NIHSS and disability.  There are folks with NIHSS score of 4 who can walk into the Emergency Department, and there are folks with the same score or lower who are functionally incapacitated.  All this means it’s a struggle to provide an individualized estimate of the benefits, risks and alternatives in consent for tPA.

This is a lovely, short, qualitative survey of a handful of (mostly) neurology consultants in the United Kingdom, asking a few questions regarding the diagnostic process, shared decision-making, and consent for thrombolysis.  Not all consultants surveyed seemed to appreciate the challenges, but others recognized limitations in the data, as well as how difficult it made informed consent:

“I think there needs to be em, err a minimum standard, standardised information available based on what you believe is the right interpretation of the trial. We have to remember that this is based on em, err limited number of randomised trials ….. This is a particularly heterogeneous disease it cannot be applied to a single patient, I think the predictions em in model could be designed but again I don’t think it can be predicted for an individual group of pa-, individual patients so we believe these are the kind of risks and benefits but you know it cannot be predicted to the individual patient.”

Other physicians commented upon the challenges of making a rapid, certain diagnosis, and the inadequate demands made upon patients and families to choose in a time-compressed setting.  Overall, it’s an interesting little read.

“Risk communication in the hyperacute setting of stroke thrombolysis: an interview study of clinicians”
http://emj.bmj.com/content/early/2014/05/16/emermed-2014-203717.short

tPA: We Don’t Need No Stinkin’ Consent!

Yes, this the brave future imagined by pro-tPA colleagues:  there are neurologists in a van down by the river, and they’ll drive right to your house and give you tPA – without your consent!

This is a research letter from JAMA, in which researchers from UCSF performed a survey of patient preferences through an online cohort representative of the adult U.S. population over 50 years of age.  These authors, as they would lead you to believe, asked participants to compare their desire to receive CPR after cardiac arrest with their desire to receive tPA after a stroke.  75.9% of surveyed participants wanted CPR and 76.2% wanted tPA.  Therefore, these authors conclude:

“… there are equally strong empirical grounds for presuming individual consent to thrombolysis for stroke as for presuming individual consent to CPR.”

I am not an ethicist, so I’m unable to precisely articulate how odd this comparison is at face value.  Would any therapy patients would choose 75% of time mean we ought to presume consent?  Is CPR the “gold standard” for emergency consent?  There are interesting questions regarding how this data ought to be interpreted in the context of emergency consent I’m not qualified to answer.

However, I am qualified to comment on their methodology, i.e., the best way to get the answer you want: ask a question in such a way they’ll answer how you intend.  How did they ask patients if they wanted CPR?  They showed them a “depiction of probabilistic outcomes after paramedic-initiated CPR”.  This depiction is not provided in the text, only a reference to an article they used to make it.  For tPA?  They used a graphical depiction of the benefits of tPA from this article.  They do not specify which graphical depiction they used, but the final product of the previous pro-tPA physicians was this, Figure 3:

With a graphic like this, is it any wonder the patients surveyed were amenable to tPA?  Interestingly, the authors who created the graphical depiction state this graphic “complements the numeric text of a national patient education tool developed jointly by US neurology, emergency medicine, and stroke patient organizations.”  The link in their citations is broken, but I have found a reproduction here, which contains the following fantastic isolated quote:

“If given promptly, 1 in 3 patients who receive tPA resolve their symptoms or have major improvement in their stroke symptoms.”

It boggles the mind ACEP was complicit in approving this horrible flyer.  As you can now see, this seemingly trivial document has since catastrophically mutated into the terrifying basis of giving tPA without informed consent.

“Testing the Presumption of Consent to Emergency Treatment for Acute Ischemic Stroke”
http://jama.jamanetwork.com/article.aspx?articleid=1861784

There’s Been A Drive-By Lysing!

If you’ve been keeping up, a couple weeks ago JAMA had a theme issue for Neurology – which nowadays, apparently, is mostly tPA.  And, the latest and greatest – concierge Neurology!  In which they come to your house to give you lytics.

This is the Prehospital Acute Neurological Treatmentand Optimization of Medical care in Stroke Study (PHANTOM-S), conducted in Berlin, Germany, using the Stroke Emergency Mobile (STEMO) vehicle.  They compared time-to-thrombolysis during 46 weeks of standard care with 46 weeks of STEMO period – and, within STEMO period, operation of the vehicle was a week-on/week-off deployment.  Unsurprisingly, driving the tPA to the patient shaves 25 minutes off the alarm to tPA time.  Success!

MedPage Today, with it’s usual insightful analysis, breaks out a table of glowing secondary outcomes – improvements in in-hospital all-cause mortality, discharge to home, symptomatic intracranial hemorrhage, and overall tPA complications …

… before acknowledging all these improvements occurred even when the STEMO wasn’t deployed, and it was rather general stroke care improvements over the study period reflected in these secondary outcomes.  Additional praise is provided by James Grotta, who has started his own mobile stroke unit in Houston.  And, finally, Associated Editor Jeff Saver, of endless tPA conflict-of-interest disclosures, chimes in for the Editor’s audio summary.

I think it’s clear, between this and its preceding pilot study, that it is possible to drive a bus around with a stroke neurologist and a CT scanner and rule out intracranial hemorrhage.  The main concern might be over-treatment of stroke mimics, but these authors state the same number of patients treated in all observation windows ultimately received non-stroke diagnoses.  However, they report a baseline stroke mimic treatment rate of 2.2% – which is line with other literature describing institutions that don’t go looking very hard for non-stroke diagnoses after tPA.  Other institutions that require MRI signs of ischemic lesions have stroke mimic rates up to 15.5%, so I wouldn’t place much stock in this specific statistic as a measure of quality.

The last issue – a reasonable case can be made for safety as long as there’s a neurologist riding shotgun in the ambulance.  However, you’ll have to find neurologists willing to take such emergency call and support their salaries while they wait for deployment, which will end up being logistically and financially unworkable.  The next step, I presume, will be pre-hospital telestroke where paramedics are supervised by a remote neurologist.  A bright, or dim, future, depending on your view of tPA.

“Effect of the Use of Ambulance-Based Thrombolysis on Time to Thrombolysis in Acute Ischemic Stroke”
http://jama.jamanetwork.com/article.aspx?articleid=1861800