Mass general Hospital. US: Tissue plasminogen activator (tPA) is the only approved drug for
ischemic stroke, those 85 percent of strokes caused by thrombosis in the
brain. After four and a half hours from stroke onset, the risk of brain
hemorrhaging in response to tPA increases. Guidelines recommend that
patients entering the hospital should receive tPA within 4.5 hours from
the time they were last known to be well, and that it should be given
within 60 minutes of arriving at the hospital (the “door-to-needle,” or
DTN, time), but many patients do not arrive in time and many emergency
departments cannot marshal resources quickly enough.
Community hospitals
also often lack rapid access to a neurologist and will not administer
tPA without one.
As a result, less than a third of eligible stroke patients receive
tPA within the recommended DTN time1, almost 20 years after its
introduction and despite strong evidence that rapid treatment with tPA
translates into better patient outcomes.2 At Massachusetts General
Hospital, Lee Schwamm, MD, Director of the Mass General Stroke Services
within the Institute for Heart, Vascular and Stroke Care, Director of
the Partners Telestroke Center and Vice Chairman of the Department of
Neurology, aims to increase the number of patients treated with tPA,
accelerate the DTN time, and promote telestroke programs that connect
neurologists with community hospitals, effectively converting them into
high-performance stroke centers.
Target: Stroke Interventions Improve Clinical Outcomes
Mass General was one of 1,030 Get With the Guidelines-Stroke
(GWTG-Stroke) hospitals across the United States participating in
Target: Stroke, a quality improvement program based on the rationale
that rapid treatment with tPA translates into better patient outcomes.3
The primary goal of the quality improvement program was to ensure that
at least 50 percent of patients receiving tPA in the U.S. were receiving
it within 60 minutes of hospital arrival. The study, published in JAMA
in April 2013,4 followed 27,319 ischemic stroke patients who received
tPA during a pre-intervention period between 2003 and 2009, and 43,850
during a post-intervention period from 2010 to 2013.
The intervention entailed implementing 10 evidence-based strategies,
which included pre-notification of hospitals by EMTs to activate the
stroke team; rapid acquisition and interpretation of brain imaging;
premixing tPA for high-likelihood candidates; and a stroke team-based
approach. The proportion of patients receiving tPA in 60 minutes or less
increased by 1.36 percent per year in the pre-intervention period and
by 6.2 percent in the post-intervention period, and clinical outcomes
(mortality, discharge to home, ambulatory status, symptomatic
intracranial hemorrhage) all improved post-intervention. Importantly,
the accelerated pace of improvement in the post-intervention period
shortened the projected time to reach the objective of the intervention
by 10 years. By the fourth quarter of 2013, the objective had been
surpassed, with 53.3 percent of tPA patients being treated in 60 minutes
or less, a significant rise from the 26.5 percent who met the time
target goal in early 2003.
To determine whether clinical improvements were attributable to
earlier tPA administration or to general improvements in care for all
stroke patients, the study compared outcomes of stroke patients at the
same GWTG-Stroke hospitals who did not receive tPA. In one example,
reduction of in-hospital mortality improved for non-tPA patients by 4
percent, but improved 11 percent for tPA patients. “This is the first
study to show that in real-world practice, tPA works best the faster you
give it, and that faster treatment saves lives and reduces bleeding
complications,” Dr. Schwamm said.
Distinguishing Stroke Mimics From Strokes
One unintended consequence of the effort to improve DTN time for tPA
might be an increase in false positives, given the rush to diagnose and
treat patients. Seizures, epilepsy, migraines, cardiovascular
morbidities and diabetes can all mimic classic stroke symptoms: facial
weakness, limb weakness, speech difficulty and altered level of
consciousness. While treating such stroke mimics (SMs) with tPA
generally does not harm patients, unless they have damaged tissue that
could hemorrhage, Dr. Schwamm’s team saw this as a costly and avoidable
drain on resources. In connection with telestroke programs that use
telecommunication technologies to evaluate stroke patients remotely, Dr.
Schwamm determined that SM patients were approximately 10 years younger
than patients with true stroke syndromes and were less likely to have a
history of hypertension, atrial fibrillation and heart failure. Two
striking indicators of SM are an absence of facial weakness and presence
of a seizure disorder. His team developed a prediction rule based on
six variables (age, history of atrial fibrillation, hypertension,
seizure, facial weakness on exam and moderate to severe stroke as
measured by the NIH Stroke Scale) that help telestroke consults
differentiate between SMs and patients with probable ischemic stroke.5
Dr. Schwamm’s ultimate goal is to have the model for stroke medicine
emulate more closely that of cardiac emergencies, with its coordinated
and specialized teams. Despite the absence of new drugs, better stroke
treatment and outcomes are achievable with existing medications. It does
not require a new invention, a new paradigm or new costs, but rather an
intensive effort to prioritize more rapid tPA administration.
References
1 Jauch, E.C., J. L. Save, H. P. Adams Jr., et al. American Heart
Association Stroke Council; Council on Cardiovascular Nursing; Council
on Peripheral Vascular Disease; Council on Clinical Cardiology.
”Guidelines for the early management of patients with acute ischemic
stroke: a guideline for healthcare professionals from the American Heart
Association/American Stroke Association.” Stroke. 2013;44(3):870-947.
2 Ibid
3 Fonarow, G. C., E. E. Smith, J. L. Saver, 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(7):750-758.
4 Fonarow, G. C., X. Zhao, E. E. Smith et al. 2014. “Door-to-Needle
Times for Tissue Plasminogen Activator Administration and Clinical
Outcomes in Acute Ischemic Stroke before and after a Quality Improvement
Initiative.” JAMA 311 (16): 1632–40. doi:10.1001/jama.2014.3203. 5 Ali,
Syed F., Anand Viswanathan, Aneesh B. Singhal, Natalia S. Rost, Pamela
G. Forducey, Lawrence W. Davis, Joseph Schindler, et al. 2014. “The
TeleStroke Mimic (TM)-Score: A Prediction Rule for Identifying Stroke
Mimics Evaluated in a Telestroke Network.” Journal of the American Heart
Association 3 (3): e000838. doi:10.1161/JAHA.114.000838.
Contributor
Lee H. Schwamm, MD
- Executive Vice Chairman, Neurology
- Director, Stroke Services and Partners TeleStroke Center