ACE Inhibitors Not Needed for Many Heart Disease Patients,
According to New Study
New Orleans, LA, Nov. 7, 2004 -- Many heart disease patients who
are already receiving state-of-the-art therapy do not benefit from
additional treatment with angiotensin converting enzyme (ACE) inhibitors,
according to results of a new study funded by the National Heart,
Lung, and Blood Institute (NHLBI), part of the National Institutes
of Health. The study provides the most definitive evidence to date
of the effect of the drug in stable heart disease patients whose
heart function was shown to be at normal or near-normal levels, and
whose heart disease was already well managed. Researchers found that
ACE inhibitors do not lower the risk of cardiovascular death, heart
attack, or the need for coronary revascularization (bypass surgery
or angioplasty to restore blood flow to clogged arteries) in these
patients.
Results of the Prevention of Events with Angiotensin Converting
Enzyme Inhibition (PEACE) are being presented November 7 at
the American
Heart Association Scientific Sessions in New Orleans. They will
also be published online concurrently by the New England Journal
of Medicine
and in the journal’s November 11 printed issue.* An editorial
accompanies the article.
The American Heart Association currently recommends ACE inhibitors
for all patients who have had a heart attack and others with
coronary or other vascular disease. ACE inhibitors are a type
of drug called
vasodilators, meaning they cause blood vessel walls to widen
or relax, thereby lowering blood pressure; they are one of
several
classes
of drugs that are recommended for treating high blood pressure.
Clinical studies have also found that ACE inhibitors improve
survival and
reduce the risk of heart attack among patients with heart failure,
a condition in which the heart muscle is no longer pumping enough
blood throughout the body. In addition, the drug has been shown
to help prevent heart failure in some patients with moderate
to severe
ventricular dysfunction, or abnormalities in the lower chambers
of the heart.
“Although ACE inhibitors have been proven to help patients
with heart failure, until now it wasn’t clear whether
all patients with coronary heart disease benefit from this
class of drugs,” said
NHLBI Acting Director Barbara Alving, M.D. “These results
could significantly change clinical care of perhaps millions
of Americans
with heart disease.”
“This study indicates that many patients with coronary
heart disease whose heart muscle is in good shape and who receive
intense treatment
including revascularization and lipid-lowering drugs do not gain
extra cardiovascular protection from ACE inhibitors,” added
Eugene Braunwald, M.D., who co-chaired the study with colleague
Marc Pfeffer, M.D. Both are in the Cardiovascular Division of
Brigham and Women's Hospital in Boston.
“These lower-risk patients can avoid side effects and the added
expense of ACE inhibitors without putting themselves at additional
risk for
cardiovascular complications,” Dr. Braunwald said. The
drug’s
side effects include cough, fainting spells, and a rare but serious
allergic reaction known as angioedema.
Heart disease is the single leading cause of death in the
United States. More than 13 million adults have coronary heart
disease,
putting them at increased risk for heart attack, sudden death,
angina, heart failure, and stroke. Most patients with coronary
heart disease,
including heart attack survivors, however, do not have heart
failure or ventricular dysfunction. PEACE was designed to test
whether ACE
inhibitors provide added benefits to this group of heart disease
patients with relatively good heart function.
The PEACE trial involved nearly 8300 participants who did
not have heart failure, and who had normal or near normal left
ventricular
function, as evidenced by left ventricular ejection fraction
of greater
than 40 percent. (The ejection fraction is an indication of the
amount of blood that is pumped out of a filled ventricle; a normal
rate
is 50 percent or more.) The average age of participants when
they started the trial was 64 years. The study was conducted
at 180 clinical
sites in the United States, Canada, Puerto Rico, and Italy.
All of the participants followed recommended treatments for
heart disease as warranted. For example, 70 percent were on
lipid-lowering
medications (drugs to lower the level of LDL or “bad” cholesterol
in the blood) and 72 percent had previously had coronary revascularization
when they enrolled in the trial. Participants were then randomized
to either take the standard dosage (4 mg/day) of the ACE inhibitor
trandolapril (Mavik), or an inactive placebo. The drug was provided
by Abbott Labs/Knoll.
After an average follow-up of 4.8 years, the same proportion
(about 22 percent) of participants in each group died from cardiovascular
disease (CVD), had a heart attack, or needed revascularization.
The results did not differ when the researchers adjusted for
the
participants’ age,
gender, or history of heart attack, transient ischemic attack, diabetes,
or high blood cholesterol. Similarly, there were no differences based
on which heart disease therapies participants followed during the
study. Although trandolapril lowered systolic blood pressure (the
top number in a blood pressure reading) by an average of 4.4 mm Hg,
the reduction did not have a significant effect on the patients’ outcomes.
“PEACE tells us that patients with coronary disease
and normal or only mildly reduced heart function do not benefit
from ACE inhibitors
unless the drug is being used to treat another condition, such
as high blood pressure,” noted Michael Domanski, M.D.,
head of the NHLBI Clinical Trials Scientific Research Group,
and a project
officer of the study. “The entry criteria in PEACE can
be used to help physicians decide which patients do not need
ACE inhibitors.”
PEACE was the final in a series of three large clinical trials
worldwide to test whether ACE inhibitors benefit heart disease
patients who
do not have heart failure. The participants in the PEACE trial
were at lower risk both at baseline and after treatment compared
to participants
in the two earlier studies. Furthermore, although all three trials
enrolled only patients who had no known heart failure or ventricular
dysfunction, only PEACE used an ejection fraction found to be
normal or slightly below normal using standard imaging tests
as a key
criterion for enrollment. The two earlier trials did not document
the participants’ ejection
fractions; thus, these participants could have had moderate to
severe ventricular dysfunction.
“While the results from the PEACE study demonstrate
that many patients with heart disease who are already receiving
state-of-the-art therapy
may not also need ACE inhibitors, it is important to remember
that these drugs continue to be recommended for patients with
heart failure
or ventricular dysfunction,” said Yves Rosenberg, M.D.
of NHLBI. Dr. Rosenberg is co-project officer of PEACE.
Approximately 5 million Americans have heart failure. Common
causes of heart failure include coronary heart disease and high
blood
pressure. Based on the NHLBI’s Framingham Heart Study,
approximately 22 percent of men and 46 percent of women who survive
a heart attack
will be disabled by heart failure within six years.
To interview Drs. Domanski or Rosenberg, please contact the
NHLBI Communications Office at (301) 496-4236. To interview
Dr. Braunwald
or Dr. Marc Pfeffer, co-chairs of the PEACE writing group, please
contact Amy Dayton Smith at 617-534-1600.
NHLBI is part of the National Institutes of Health (NIH),
the Federal Government's primary agency for biomedical and
behavioral
research.
NIH is a component of the U.S. Department of Health and Human
Services. NHLBI press releases, fact sheets, and resources on
heart disease
can be found online at www.nhlbi.nih.gov. For more information
about PEACE, visit http://www.bsc.gwu.edu/peace/.
* The PEACE Trial Investigators. Angiotensin-converting–enzyme
inhibition in stable coronary artery disease. N Engl J Med 2004;351:2058-68.
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