Thrombolytic Therapy for Acute Stroke

372 Pages·2005·3.81 MB·English

by  Gregory J. del Zoppo MD

Thrombolytic Therapy
for Acute Stroke
C C N
U R R E N T L I N I C A L E U RO LO G Y
Daniel Tarsy, , S E
MD ERIES DITOR
Thrombolytic Therapy for Acute Stroke, Second Edition, edited by Patrick D. Lyden,
2005
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Thrombolytic Therapy
for Acute Stroke
Second Edition
Edited by
Patrick D. Lyden,
MD
USCD Stroke Center, University of California, San Diego
and Veteran’s Affairs Medical Center
San Diego, CA
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Library of Congress Cataloging-in-Publication Data
Thrombolytic therapy for acute stroke / edited by Patrick D. Lyden.-- 2nd ed.
p. cm. -- (Current clinical neurology)
Includes bibliographical references and index.
ISBN 1-58829-398-X (alk. paper)
1. Cerebrovascular disease--Chemotherapy. 2. Thrombolytic therapy.
I. Lyden, Patrick D. II. Series.
RC388.5.T476 2005
616.8'10651--dc22
2005000628
Dedication
This book is again dedicated to our families, who daily cope with the vagaries,
inconveniences, and turmoil surrounding our involvement in a Stroke Team. It is
also dedicated to the patients who volunteered to participate in the placebo-con-
trolled trials of thrombolytic stroke therapy: a more courageous and selfless group
activity, on such a scale, may not be seen again in medical research.
v
Series Editor’s Introduction
It often takes time for a new therapeutic modality to mature into an accepted
treatment option. After initial approval, new drugs, devices, and procedures all go
through this process until they become “vetted” by the scientific community as
well as the medical community at large. Thrombolysis for treatment of stroke is no
exception.Thrombolytic Therapy for Acute Stroke, Second Edition comes four years
after the first edition and provides a very comprehensive, updated perspective on
the use of intravenous rt-TPA in acute stroke. The authors provide longer term
follow-up on the pivotal clinical trials that led to Food and Drug Administration
approval, data concerning phase 4 trials in larger numbers of patients, and, most
importantly, the community experience that has accumulated since its release. They
add to this the latest promising information concerning intra-arterial thrombolysis,
which is still under investigation and more speculative sections concerning
possible new avenues of clinical research such as combining intravenous throm-
bolysis with neuroprotective therapies or intra-arterial thrombolysis. A wealth of
factual information is supplemented by chapters containing sage opinion from Drs.
Lyden and Caplan concerning the logistical, economic, and procedural issues that
have been generated since the advent of this technology. Importantly, diagnosis
does not take a back seat to therapeutics as illustrated by sections devoted to evalu-
ation of the stroke patient, very useful illustrative cases and clinical comments,
and chapters on the latest in imaging as applied to this field. Practical chapters
concerning how to run a stroke code and hospital acute stroke protocols are espe-
cially helpful and are must reading for anyone contemplating this therapy for their
institution.
As pointed out by Dr. Lyden, the implementation of thrombolytic therapy has
been an uphill battle from the start. It is sobering to read about the disappointing
results of early clinical trials, many of which startlingly were carried out without
modern imaging. The pivotal NINDS trial for intravenous rt-TPA in stroke required
unusual dedication and effort to succeed. Even after thrombolysis was demonstrated
to be effective, concerns for its safety and skepticism regarding the logistics of
speedy patient evaluation created some inertia and reluctance among clinicians.
For example, neurologists on the front line were expected to provide more than
“diagnose and adios” if this treatment was going to have an impact on stroke
morbidity. In fact, however, this book makes it clear that the opposite has occurred.
Neurologists and other health care providers, emergency room medical and nursing
staffs, hospital administrators, health care officials on the local and national level
and many others have been energized to create and nourish acute stroke teams
vii
viii Series Editor’s Introduction
throughout the country that have revolutionized the treatment of stroke.
Presently, however, the proportion of acute stroke patients eligible to receive throm-
bolytic therapy who are actually treated remains very small. The wisdom and
knowledge provided in this volume needs to be spread throughout the medical com-
munity and the public so as to maximize its benefit and fulfill its promise.
Daniel Tarsy, MD
Department of Neurology
Beth Israel Deaconess Medical Center
Harvard Medical School
Boston, MA
Preface
Thrombolytic Therapy for Acute Stroke, Second Edition remains intended for
any physician seeking to learn to use thrombolytic therapy for acute stroke. As in
the first edition, we present facts and data for the reader to consider; opinion is
clearly segregated and labeled (see the debate chapters provided by Dr. Lou Caplan
and myself.) We updated many chapters extensively, and added sections pertaining
to new technology. Notably, some of the leading developers of stroke-magnetic
resonance imaging contributed a key new chapter that hopefully will set the stage
for improved patient selection. Yet, computed tomography will remain the most
widely available imaging procedure for at least another decade, and Professor
Rudiger von Kummer extensively revised this important chapter as well.
Patient selection remains the trick, and all chapters describing the background,
use, and nuance of thrombolytic therapy were revised extensively. Everything one
needs to know, and then some, is provided: rationale, preclinical trials, early trials,
and pivotal trials. Practical how-to chapters will guide the reader in treating acute
stroke patients, both with and without thrombolytic therapy. To enable the reader to
practice the knowledge gained, we replaced all the case scenarios with new,
detailed practice cases. Unique, I think, among stroke therapy books, this case
section will allow the reader to put into play all of the facts and advice contained in
the remainder of the book. Practicing these scenarios will enable practitioners to be
as ready as possible for their first case.
The history of thrombolytic therapy for stroke makes for remarkable reading; as
evidenced by the series of pilot experiments described in Chapter 6. The first uses of
thrombolysis in humans were disasters, but no one knew going in that the risks were so
high. Following those horrible results, nearly 20 years passed before the medical
community again attempted thrombolytic therapy in stroke. That Greg del Zoppo,
Justin Zivin, and especially John Marler were able to inspire the large, randomized
trials of the early 1990s, based on critical animal experiments, is impressive.
As predicted in the preface to the first edition, to this day there remains no
medical experiment of comparable size, complexity, or courage from patients and
families as the NINDS rt-PA for Acute Stroke Trial. It is said, even now almost a
decade after the landmark trial, that thrombolytic therapy can be used only in
specialized centers full of “commandos” willing to take call and respond to Code
Stroke calls on a moment’s notice. As the case scenarios demonstrate, the com-
mando model is certainly on the wane. Stroke patients now receive thrombolytic
therapy in a variety of venues, and from a wide range of physicians, including emer-
gency, internal, and family medicine practitioners. There is no doubt, however, that
expertise and dedication to learning the protocol is required, as elegantly docu-
ix
x Preface
mented by the Cleveland Area survey, among other studies: a new chapter has been
added that surveys the community implementation of thrombolytic stroke therapy.
The personal toll the original NINDS trial exacted from the authors—my friends
and colleagues—is now nearly the stuff of legend in clinical neurology. In some
ways, the legends both underplay and overstate the struggle we endured, but that is
another story. The important point, to me, is that in many centers thrombolytic
stroke therapy is now routine, as integrated in the daily functions of the medical
center as Code Blue or cardiac transplantation. Getting us to this point required
creativity, sacrifice, extreme effort, and in some cases heroism. The hard job is
done now, and the task remains to diffuse the knowledge throughout the medical
profession and in public: too few patients receive good stroke care, and during the
time it took to read this preface, two more patients in the United States suffered
disabling strokes. Thrombolytic therapy for stroke reduces disability; time is brain
my friends, and the clock is ticking.
Patrick D. Lyden, MD