WIZARD Results Published
By Mike Upchurch

Results from a landmark DCRI study have cast a shadow over the theory that a particular bacterial infection significantly contributes to heart disease. The analysis, published in this week's issue of the Journal of the American Medical Association, showed no benefit of weekly antibiotic therapy in patients who had suffered a heart attack and showed evidence of bacterial infection.

A few small trials of antibiotic therapy have shown reduced rates of coronary events in patients with a previous heart attack or other acute coronary syndromes. But a larger trial, ACADEMIC, showed no difference in event rates between patients taking a placebo and those taking azithromycin, the same antibiotic studied in the DCRI's study, WIZARD (Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders).

WIZARD enrolled over 7000 patients who had suffered a heart attack and who showed elevated antibody levels for a particularly infectious bacteria called C. pneumoniae. Those patients were randomized to either placebo or azithromycin at a dose of 600 mg 4 times daily for 3 days and then 600 mg weekly for 11 weeks. Investigators followed the patients for 2 years, and then measured a composite end point of death from any cause, repeat heart attack, need for surgical intervention, and hospitalization for angina.

Analysis of the data found no connection between azithromycin use and a reduction in this endpoint, even after adjustment for the patients' baseline levels of infection. The news was not completely negative however, according to lead author, the DCRI's Dr. Chris O'Connor.

"We did see a trend [in favor of azithromycin] in men, patients with diabetes, and smokers. In addition, a preliminary post hoc analysis appeared to show an early benefit shortly after azithromycin treatment but this was not sustained over the observation period [of 2 years]," he said.

Dr. O'Connor went on to add that "no conclusions can be drawn on the efficacy of this drug in other patient populations, nor on the possible efficacy of other antibiotics."

While some doctors have begun prescribing antibiotics to their heart patients based on the previous, small studies that were positive, Dr. O'Connor said that this practice was premature.

In an accompanying editorial, Dr. Sorin Pislaru of the Mayo Clinic and Dr. Frans Van de Werf of the University of Leuven in Belgium speculated that studies of larger doses of antibiotics or different treatment schedules may still provide some cardiovascular benefit.

Drs. Rowena Dolor and Mitch Krucoff from the DCRI also contributed to WIZARD. Kathi Lucas was the DCRI Project Lead for the study. The trial was sponsored by Pfizer Global Research and Development.