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CHICAGO, IL -- Initiating low-dose beta-blockers prior to
discharge in heart failure patients hospitalized for worsening
symptoms significantly improves the use of a drug that has been
shown in previous studies to reduce death and morbidity by more
than 35 percent.

This finding is significant, said researchers from Duke
University Medical Center and Northwestern University, because
standard heart failure practice guidelines suggest waiting a
period of two to four weeks after discharge prior to initiating
beta-blocker therapy. This recommendation was based on a
concern that beta-blocker initiation too soon after a
hospitalization for heart failure may worsen heart failure
symptoms, said the researchers.

Beta-blockers block the stimulatory effects of the
neurohormones epinephrine and norepinephrine, the so-called
"fight-or-flight" hormones. By blocking these hormones,
beta-blockers reduce the stress on the heart and reverse
myocardial remodeling. Most importantly, they have been shown
to improve survival and reduce the need for hospitalization by
35 percent in several large-scale, prospective, randomized
clinical trials. Despite these beneficial effects, it is
estimated that nationally still only 30 to 40 percent of
eligible patients receive beta-blocker therapy.

Such low usage led the researchers to initiate a trial to
determine whether starting beta-blocker therapy in the hospital
setting would improve usage. The results of that trial,
reported today (Nov. 18, 2002) at the 75th annual scientific
session of the American Heart Association, show that beginning
beta-blocker therapy in-hospital can achieve a 91 percent usage
rate 60 days after discharge.

"If we can dramatically improve the rate of beta-blocker
usage by initiating therapy in-hospital, that would make a
major impact these patients' lives," said Duke cardiologist
Christopher O'Connor, M.D., who along with Duke?s Wendy Gattis,
Pharm.D., and Northwestern's Mihai Gheorghiade, M.D., directed
the trial.

"Strategies like this are extremely important as the death
and disability of this group of patients continues to be
alarmingly high despite the availability of life-saving
therapies," O'Connor said.

Heart failure is marked by the inability of the heart
muscles to pump enough oxygen and nutrients in the blood to the
body's tissues. Also known as congestive heart failure, its
many causes include coronary artery disease, high blood
pressure, previous heart attack and valve problems.

An estimated 4.7 million Americans suffer from heart
failure, with 500,000 new cases reported each year, and
according to the researchers, it is the only cardiovascular
disease that is rising in incidence. Once diagnosed with heart
failure, about 50 percent of patients will die within five
years.

For the trial, the researchers randomized 363 heart failure
patients to one of two groups: one received the beta-blocker
carvedilol prior to hospital discharge, while the other group
could receive a beta-blocker at their physician?s discretion,
but it could not be started until at least two weeks after
discharge, according to current standard practice. After 60
days, 91 percent of patients who were started on carvedilol
prior to hospital discharge were still taking a beta-blocker,
while 73 percent of physician-discretion group were taking
them, a difference that was highly statistically
significant.

In addition, patients initiated on carvedilol pre-discharge
were closer to reaching the target beta-blocker dose at 60-days
as compared to the patients in the post-discharge physician
discretion arm, a finding that was also statistically
significant.

"Not only was the usage rate higher, but we showed that
early beta-blocker treatment was safe," Gattis said. "The
patients initiated on carvedilol prior to discharge did not
have a higher rate of serious adverse events including
worsening heart failure, hypotension, or bradycardia as
compared to the patients initiated post-discharge. Other
important clinical events such as death or rehospitalizations
were also less frequent at 60 days in the early treatment
group, but because of small patient numbers and the short
duration of follow-up did not reach statistical
significance."

The safety issue is important, the researchers said, because
until recently, initiation of beta-blockers was not recommended
in patients with a recent episode of heart failure worsening.
These new data should help encourage physicians to change
long-held prescribing habits. The researchers said that many
physicians, upon seeing their heart failure patients stabilized
in-hospital, are hesitant to add another medication to the mix
out of concern that patients' symptoms may worsen.

"We hope to change physicians' minds and get them to look at
in-hospital beta-blocker use as a method to increase the
overall use of beta-blockers in this population. Increased use
of this evidence-based therapy will likely translate into
improved outcomes for patients based on data from previous
randomized trials," Gattis said.

O'Connor sees a similarity between the low rate of usage of
beta-blockers for heart failure and another class of heart
medications known as statins, which have been proven to lower
cholesterol levels and, more importantly, to reduce the risk of
death and myocardial infarction in patients with coronary heart
disease.

"For a long time, the usage rate of statins was about 20
percent, even though clinical trials clearly demonstrated their
effectiveness," O'Connor. "Then, later trials showed that it
was not only safe to start statins in heart attack patients
while still in the hospital, but that this early initiation of
therapy led to a higher rate of use after discharge."

Heart failure often leaves patients exhausted and
breathless, and the normal activities of these patients can be
severely restricted. Although there is no cure for the
disorder, a variety of drugs are often used in the treatment of
heart failure, including ACE-inhibitors, beta-blockers,
diuretics and digoxin.

Patients with heart failure can be a difficult group to
treat, said the researchers. They are frequently admitted to
the hospital to care for the symptoms of the disease, and
almost one-third will be re-admitted to the hospital within the
first three months after discharge.

"It is hoped that implementing beta-blocker therapy early
will ensure that patients are actually treated with
evidence-based therapies, which indirectly should also
contribute to improving outcomes for heart failure patients,"
Gattis said.

The current trial, dubbed Initiation Management Predischarge
Process for Assessment of Carvedilol Therapy for Heart Failure
(IMPACT-HF), was funded by GlaxoSmithKline, Philadelphia, the
maker of carvedilol. O'Connor, Gattis, and Gheorghiade receive
research support from and are consultants to
GlaxoSmithKline.

The Duke researchers and colleagues from Northwestern
University, UCLA, UCSD, Cleveland Clinic, and University of
Texas Southwestern are rolling out OPTIMIZE-HF (Organized
Program To Improve Treatment of Hospitalized Patients with
Heart Failure), a hospital- and web-based registry program that
hopes to enroll up to 50,000 heart failure patients at
approximately 500 hospitals across the United States. The goal
of this initiative is to improve the management of heart
failure patients.

OPTIMIZE-HF will determine whether or not physicians are
taking advantage of the latest findings from clinical trials
and incorporating them into patient care. Hospitals will
receive feedback on how they are performing compared to other
hospitals.