Embargoed for Release: November 7, 2004
Embargoed for Release: November 7, 2004
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.
* The PEACE Trial Investigators. Angiotensin-converting enzyme inhibition in stable coronary artery disease. N Engl J Med 2004;351:2058-68.