ACE Inhibitors Not Needed for Many Heart Disease Patients, According to New Study
New Orleans, Louisiana 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,
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.