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ANAHEIM, CA. -- While clot-busting drugs known as
thrombolytics have shown great effectiveness in treating heart
attack patients in hospital emergency rooms, a new Duke
University Medical Center analysis provides additional evidence
that great care must be taken in deciding which patients should
receive this life-saving therapy.

Many patients brought to emergency rooms with symptoms of
heart attacks are given thrombolytic drugs to open blocked
arteries and keep the heart from being starved of oxygen-rich
blood. Nearly 1 percent of the patients, however, suffer from
potentially lethal bleeding in the brain known as intracranial
hemorrhage (ICH).

The Duke researchers looked at data collected in a recent
large multi-center trial and found that 2 percent of the
patients treated with thrombolytics were later found to be
inappropriate candidates and, furthermore, that these patients
had significantly worse outcomes than the other 98 percent.
While this finding was not unexpected, the researchers say the
results provide a cautionary note to physicians practicing in
the community who may not follow the same strict screening
protocols used when enrolling patients in formal clinical
trials.

Cardiologist Dr. John Alexander of the Duke Clinical
Research Institute (DCRI) prepared the results of the Duke
analysis for presentation during the 74th annual scientific
sessions of the American Heart Association in Anaheim,
Calif.

"For physicians, the risk of ICH is the No. 1 limiting
factor in the use of thrombolytic drugs," Alexander said. "If 2
percent of patients in the very controlled setting of a
clinical trial were getting a drug that they shouldn't, it is
highly likely that a higher percentage of patients are getting
thrombolytics inappropriately in the real world of clinical
practice.

"While we don't want to alarm people unnecessarily, the
results of this study should make doctors pay extra attention
before using these drugs," he said.

In his analysis, Alexander looked at the data collected
during a 16,949-patient trial known as ASSENT-2 that compared
the effectiveness of two different thrombolytic agents ? t-PA
or TNK, a genetically altered version of t-PA. Alexander found
that 324 patients (2 percent) received thrombolytics but were
later found to have medical conditions that should have ruled
them out.

These patients with medical contraindications were three
times more likely to die 30 days after treatment (15.3 percent
vs. 5.7 percent) and were more than eight times as likely (6.7
percent vs. 0.8 percent) to have an episode of ICH. There was
no difference in adverse outcomes between the two different
thrombolytics.

"When a patient comes to the emergency room with symptoms of
a heart attack, doctors must act quickly in deciding whether or
not to treat the patient with thrombolytics," Alexander said.
"On average, if thrombolytics were used in the trial, they were
started within 40 minutes of arrival in the emergency
room."

The challenge facing these doctors, Alexander explained, is
that it can be difficult to determine if a patient should be
excluded within the short period of time necessary for the
thrombolytic therapy to be effective.

The five major criteria that would exclude enrollment were:
a history of stroke or transient ischemic attack (TIA), 175
patients; hypertension, 65 patients; any minor head trauma, 39
patients; current use of anti-coagulation therapy (coumadin),
35 patients; or damage to central nervous system, 27
patients.

While all of these criteria increase the risk of a bleeding
episode, it is not always possible in the fast-moving
environment of an emergency room to be absolutely certain that
a patient doesn't have one or more of these factors, Alexander
said.

"It can be challenging in the emergency room to get a
complete medical history, but the bottom line is that the
utmost care must be taken in trying to find out as much about
these patients as possible," Alexander said.

Dr. Cecelia Bahit, until recently a cardiology fellow at the
DCRI, played an important role in the DCRI analysis.

Genentech, South San Francisco, Calif., and Boehringer
Ingelheim, Germany, funded the original ASSENT-2 trial.
Alexander's team analysis of the ASSENT-2 data was supported by
the DCRI.

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