Risk of secondary cardiac events not reduced by antibiotic treatment

Taking antibiotics weekly for a year does not reduce the risk of a heart attack or other cardiac event for patients with stable coronary artery disease, according to a University of Washington study published in a recent edition of the New England Journal of Medicine (NEJM).

Previous studies have found the bacteria Chlamydia pneumoniae in the arterial plaque of patients with coronary artery disease. Some doctors have reasoned that removal of C. pneumoniae from the system could reduce the risk of subsequent cardiac events. Prescription of antibiotics for this purpose had not been tested through a randomized clinical trial.

All US adults have been exposed to C. pneumoniae, which spreads through the air and causes pneumonia or mild repiratory disease, at some point in their lives.
This study, called the Azithromycin coronary events study, or ACES, found no benefit from treating the C. pneumoniae bacteria with an antibiotic in order to reduce the risk of heart attack or improve overall cardiac outcomes.

The investigation of whether antibiotics could be used to treat the bacteria, and therefore reduce the risk of cardiac events, was conducted at 27 different sites in the United States.
The National Heart, Lung, and Blood Institute (NHLBI) and the Pfizer Co. funded the study. NHLBI is part of the National Institutes of Health (NIH), the federal government’s primary agency for biomedical and behavioral research.

ACES researchers randomly assigned 4,012 men and women to receive either once-weekly doses of Azithromycin or a placebo for one year, starting in 1999. After an average follow-up of 3.9 years, there was no significant reduction of cardiac events, defined as death, heart attack, unstable angina, angioplasty or cardiac surgery, among participants receiving antibiotic compared to those given placebo. This lack of antibiotic effect was shown for all participants, regardless of age, gender, smoking status, or presence of C. pneumoniae antibody. The antibiotic treatment also had no effect on total mortality or on incidence of stroke.

Men and women were included in the study if they had stable coronary artery disease following a previous cardiac event such as a heart attack, angioplasty or cardiac bypass surgery. Azithromycin was selected because of its proven effectiveness against the C. pneumoniae bacteria and for its once-weekly dosing.

“This is conclusive evidence against using antibiotics to treat late stages of cardiovascular disease, but since the trial was not designed to study the role of C. pneumoniae in causing coronary heart disease, the ACES results do not tell us anything about a possible role of C. pneumoniae in the early development or acceleration of disease in the coronary arteries,” said the study’s principal investigator, Dr. J. Thomas Grayston, professor of epidemiology in the U-W School of Public Health and Community Medicine. “More study is needed to determine the role of C. pneumoniae in heart disease.”

The ACES results are confirmed and extended by the similar negative findings of the PROVE-IT trial published in the same issue of the NEJM. PROVE-IT tested a different antibiotic, a fluoroquinolone, and used a different treatment schedule with participants who were somewhat younger than those in ACES and who had an acute cardiac event at the time of their enrollment in the study.

SOURCE: “Azithromycin for the Secondary Prevention of Coronary Events.” Grayston JT, Kronmal RA, Jackson LA, Parisi AF, Muhlestein JB, Cohen JD, Rogers WJ, Crouse JR, Borrowdale SL, Schron E, Knirsch C, the ACES Investigators. N Engl J Med 2005; 352:1637-1645, Apr 21, 2005.