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The WIZARD Study: A Randomized Controlled Trial

Christopher M. O'Connor, MD; Michael W. Dunne, MD; Marc A. Pfeffer, MD, PhD; Joseph B. Muhlestein, MD; Louis Yao, MD; Sandeep Gupta, MD; Rebecca J. Benner, PhD; Marian R. Fisher, PhD; Thomas D. Cook, PhD; for the Investigators in the WIZARD Study

JAMA. 2003;290:1459-1466.

Context  Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis.

Objective  To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure.

Design, Setting, and Participants  Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001.

Intervention  The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868).

Main Outcome Measures  The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued.

Results  After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P = .23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo.

Conclusion  Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.

Author Affiliations: Duke University, Durham NC (Dr O'Connor); Pfizer Global Research and Development, New London, Conn (Drs Dunne and Benner); Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (Dr Pfeffer); University of Utah, LDS Hospital, Salt Lake City (Dr Muhlestein); Weston, Ontario (Dr Yao); Whipps Cross and St Bartholomew's Hospital, London, England (Dr Gupta); University of Wisconsin, Madison (Drs Fisher and Cook).

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Antibiotics and Coronary Heart Disease
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