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Long-Term Antibiotic Treatment of Chlamydia pneumoniae After Acute Coronary Syndrome Shows No Reduction in Cardiovascular Events

April 21, 2005

Boston, MA- While many previous animal studies have shown the association of Chlamydia pneumoniae with atherosclerotic plaques, a study done by Christopher P. Cannon, M.D. et al from Brigham and Women’s Hospital and Harvard Medical School has shown otherwise. Their study, published in the April 21, 2005 issue of The New England Journal of Medicine, showed that despite long-term treatment with a bactericidal antibiotic effective against C. pneumoniae, there was no reduction in the rate of cardiovascular events. This indicates that therapy after acute coronary syndrome should be directed away from antibiotic therapy.

Infection with various pathogens has been implicated in the development of coronary artery disease. C. pneumoniae has been proposed as a possible etiological agent for atherosclerotic plaques. Some studies with animal models suggested that long-term treatment with antibiotics might be effective in the prevention of cardiovascular events. Other studies have not shown these strong clinical indications. Thus, a trial was set up to compare the long-term treatment with gatifloxacin with that of placebo for the prevention of cardiovascular events associated with acute coronary syndrome.  Gatifloxacin is a quinolone antibiotic with bactericidal activity against C. pneumoniae.

In a double-blind, randomized, placebo-controlled study, 4162 patients were enrolled. The patients had been previously hospitalized for an acute coronary syndrome, having either acute myocardial infarction (with or without ST-segment elevation) or high-risk unstable angina within the preceding 10 days. The protocol included standard medical intervention for acute coronary syndromes plus 400 mg of gatifloxacin daily or placebo. Subjects received an initial 2-week course of therapy beginning the visit on day 15, followed by a 10-day course every month. The mean duration of the trial was two years. Blood samples for the measurement of antibodies to C. pneumoniae were obtained at baseline and at 4 months. The primary end point of the trial was death, myocardial infarction, documented unstable angina that required hospitalization, revascularization or stroke.

A Kaplan-Meier analysis revealed that the rates of primary-end point events at two years were 23.7 percent in the gatifloxacin group and 25.1 percent in the placebo group (hazard ratio, 0.95, 95 percent confidence interval, 0.84 to 1.08; P=0.41). Testing of baseline IgG antibody titers to C. pneumoniae did not identify a subgroup of patients who benefited from antibiotic treatment, including the 5 percent who had the highest baseline titers. Additionally, there were significant side effects associated with the antibiotic such as diarrhea and nausea or vomiting.

Although there has been evidence to suggest that c. pneumoniae has a role in the development of atherosclerosis, the study was not able to detect a benefit from long-term antibiotic therapy in patients who had recently been hospitalized for an acute coronary syndrome.

Co-authors: Eugene Brauwald, M.D., Carolyn H. McCabe, B.S., J. Thomas Grayston, M.D., Brent Muhlestein, M.D., Robert P. Giugliano, M.D., Richard Cairns, M.Sc., and Allan M. Skene, PhD.


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