Inflammation mediated by intracellular pathogens such as Chlamydia pneumoniae has been thought to contribute to the atherosclerotic process. Antigens to C. pneumoniae and other immunohistologic evidence have been found in connection with coronary disease. The Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders (WIZARD) study was designed to assess the effect of 12 weeks of treatment with azithromycin compared with placebo on a stable population of patients with previous myocardial infarction (MI) and evidence of C. pneumoniae infection.

Eligible patients had documented MI more than six weeks before the study, with evidence of C. pneumoniae infection. Patients meeting eligibility criteria were randomly assigned to receive azithromycin in a dosage of 600 mg once daily for three days, then once weekly for the subsequent 11 weeks, or matching placebo. Primary events included death by any cause, recurrent MI, coronary revascularization procedure (coronary artery bypass graft surgery or percutaneous coronary intervention), or hospitalization for angina, whichever came first. Secondary events included a non-coronary atherosclerotic event, such as stroke, cardiovascular death, or hospitalization for congestive heart failure.

Patients were randomized in two phases, with 3,538 participants in the first group and 4,209 in the second group; more than 90 percent completed the study treatment. Mean and median follow-up times were 25 months in the first group and 14 months in the second group.

The annualized primary event rate in the placebo group was 8.02 percent. Azithromycin treatment was associated with a 7 percent nonsignificant reduction in risk of a primary event, with no significant risk reduction for any primary event component. No significant association between C. pneumoniae titers and treatment effect was observed. A trend toward differences in risk reduction was observed in subgroups of patients. In the subgroup of patients with diabetes who also smoked, the annualized primary event rate for the primary end point was 14.6 percent with azithromycin versus 53 percent with placebo.

A 12-week course of azithromycin was not found to lower rates of death, nonfatal reinfarction, hospitalization for angina, or coronary revascularization in patients with previous MI and evidence of exposure to C. pneumoniae. Some effect of azithromycin treatment might occur in some high-risk populations; further studies are needed to confirm these observations. C. pneumoniae titers were not predictive of the development of an event during the study. The authors do not recommend instituting azithromycin treatment for prevention of recurrent coronary heart disease in patients with previous MI.