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. |