Wednesday, April 23, 2014

Target: Stroke – “Success!”

The use of tPA has evolved rapidly over the last decade.  However, despite its increasing use, proponents have been dismayed to see eligible patients were still receiving tPA within 60 minutes of ED arrival only one-third of the time.  Thus, “Target: Stroke”, a set of key strategies to improve door-to-needle time introduced in 2010.

The initiative, described in this retrospective analysis of the Get With the Guidelines-Stroke registry, is very clearly successful.  Even taking into account the limitations in data quality, there is a clear inflection point in late 2010 or early 2011 at which participating hospitals began generally improving their door-to-needle time.  By mid-2013, over 50% of eligible patients were receiving their tPA within 60 minutes.

If the authors stop there, we have a respectable paper describing a successful quality intervention.

However, they also go one step further and try to link the door-to-needle improvements to outcomes.  They observe decreases in mortality, symptomatic intracranial hemorrhage, and tPA complications, and heavily associate these observations with faster tPA use – without seriously acknowledging any alternative explanation.

But, we know there have been many changes in stroke care over the last decade.  Stroke units, swallow evaluations, temperature management, and many other advances in post-stroke care have reduced mortality and complications.  However, the authors state:
“The in-hospital mortality benefit associated with the post-intervention vs preintervention periods for patients with acute ischemic stroke treated with tPA was of greater magnitude than the improvement observed for those not treated with tPA and for patients with hemorrhagic stroke cared for during the same time frame in these hospitals, suggesting this finding was the result of more than just general improvements in stroke care and outcomes.”
… but, despite claiming this – and having clearly done the analysis – they do not provide us with this data to inspect and compare.

They also dangerously assert:
“Although there have been concerns that attempting to achieve shorter door-to-needle times may lead to rushed assessments, inappropriate patient selection, dosing errors, and greater likelihood of complications, our findings suggest that more rapid reperfusion therapy in acute ischemic stroke is feasible … with actual reductions in complications.”
… when it has been clearly observed in multiple reviews of stroke mimics, the baseline rate of intracranial hemorrhage in patients without stroke is less than 1%.  Therefore, it is entirely consistent with the existing evidence that rushing to therapy – and treating mimics – will ultimately reduce overall intracranial hemorrhage.

Regardless, it’s the expected interpretation from a group of authors with a conflicts-of-interest statement so long it’s almost comedic:
Dr Fonarow reported serving as a member of the Get With The Guidelines (GWTG) steering committee; receiving significant research support from the National Institutes of Health; and being an employee of the University of California, which holds a patent on retriever devices for stroke. Dr Smith reported serving as a member of the GWTG steering subcommittee. Dr Saver reported serving as a member of the GWTG science subcommittee; the University of California, his employer, receives funding in exchange for his services as a scientific consultant for CoAxia, Grifols, Brainsgate, Lundbeck, Ev3, and Stryker regarding trial design and conduct; and the University of California holds a patent on retriever devices for stroke. Dr Reeves reported receiving salary support from the Michigan Stroke Registry and serving as a member of several American Heart Association (AHA) GWTG subcommittees. Dr Bhatt reported serving on advisory boards for Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; serving on the board of directors for Boston VA Research Institute and the Society of Cardiovascular Patient Care; serving as chair of the AHA GWTG steering committee; being a member of data and safety monitoring committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and the Population Health Research Institute; receiving honoraria from the American College of Cardiology (editor, Clinical Trials, Cardiosource), Belvoir Publications (editor in chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), WebMD (continuing medical education steering committees); serving as associate editor for Clinical Cardiology, section editor (pharmacology) for the Journal of the American College of Cardiology; receiving research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Roche, sanofi-aventis, The Medicines Company; and performing unfunded research for FlowCo, PLx Pharma, Takeda. Dr Hernandez reported receiving AHA pharmaceutical roundtable grant 0675060N and a research grant from Johnson & Johnson; and receiving honoraria from AstraZeneca and Amgen. Dr Peterson reported receiving research grants from Lilly, Johnson & Johnson, Bristol-Myers Squibb, sanofi-aventis, and Merck-Schering Plough partnership; and serving as principal investigator of the data analytic center for the AHA/American Stroke Association’s (ASA) GWTG. Dr Schwamm reported being the principal investigator of an investigator-initiated study of extended-window intravenous thrombolysis funded by the National Institute of Neurological Disorders and Stroke (clinicaltrials.gov/show/NCT01282242) for which Genentech provides alteplase free of charge to Massachusetts General Hospital as well as supplemental per-patient payments to participating sites; serving as chair of the AHA/ASA GWTG stroke clinical work group; serving as a stroke systems consultant to the Massachusetts Department of Public Health; and serving as a scientific consultant regarding trial design and conduct to Lundbeck (international steering committee, DIAS3, 4 trial) and Penumbra (data and safety monitoring committee, Separator 3D trial). Mr Zhao and Dr Xian reported not having any disclosures.
Target: Stroke is an initiative provided by the American Heart Association/ American Stroke Association (AHA/ASA). The GWTG-Stroke program also is provided by the AHA/ASA. The GWTG-Stroke program is currently supported in part by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. The GWTG-Stroke program has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/sanofi pharmaceutical partnership and the AHA pharmaceutical roundtable.
“Door-to-Needle Times for Tissue Plasminogen Activator Administration and Clinical Outcomes in Acute Ischemic Stroke Before and After a Quality Improvement Initiative”
http://jama.jamanetwork.com/article.aspx?articleid=1861802

2 comments:

  1. The ambulance-based thrombolysis article in that same issue was also a little scary. I thought we've been through this whole stay-and-play vs scoop and go thing in the prehospital world over and over again. Then there was there whole earlier tPA=better outcomes leap of faith issue there as well... I understand this is a study that was meant to pilot further research, and that studies on clinical outcomes will come out as they are able to recruit more patients and adequately power things, but I can't help but be afraid that by reading the abstract alone, there will be folks that believe that some sort of patient-oriented outcome measure was studied and will push for more of this. And I can also imagine that if the study turns out to be negative when they look at actual clinical outcomes that it will just disappear into the wind.

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  2. It's getting embarrasing to see my peers burying their heads in the sand. So, I guess if we work for and edpm group we have a conflict of interest? Give me a break.

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