Secondary prevention of coronary artery disease with antimicrobials: current status and future directions

Over the past several decades, coronary artery disease (CAD) has become the major health problem in the Western world with more than 50% of deaths attributed to its complications. The exact causes of atherosclerosis are not clearly known, although multiple risk factors (e.g. hypertension, hyperlipidemia, diabetes mellitus, family history, and smoking) have been well described. However, these risk factors account for only about 50% of the total risk of CAD. Consequently, an ongoing search is under way to discover new risk factors for atherosclerosis as well as the basic underlying causes of progression. Although the evidence is not yet definitive, recent studies have shown that chronic infection by such bacterial organisms as Chlamydia pneumoniae, Helicobacter pylori, and a variety of dental pathogens may play a causative role in atherosclerosis. If this is true, then antimicrobial therapy may be helpful in the secondary prevention of CAD. Indeed, several small studies have already been completed testing this hypothesis. This article reviews the evidence associating these bacterial pathogens to CAD and presently available information regarding the use of antibiotics in the setting. At present, most studies evaluating the potential efficacy antimicrobials in the secondary prevention of CAD have tested the use of macrolide antibodies. Although several small preliminary studies have reported promising results favoring a clinical benefit from even short (<3 months) courses of antimicrobial therapy, the first large clinical trial, the Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders (WIZARD) study, did not show a statistically significant beneficial effect of a 3 month course of azithromycin over placebo by the end of up to 4 years follow-up. However, a statistically significant (p = 0.03) 33% reduction in death and myocardial infarction was found at 6 months, 3 months after the discontinuation of antibiotics. This robust clinical benefit, however, was not sustained over the ensuing 3.5 years of follow-up. These disappointing long-term outcomes of short-term therapy with antimicrobials may be explained by the recently discovered difficulty found in eradicating chronic vascular infections such as C. pneumoniae. It remains possible that longer term antimicrobial therapy or short-term use of more potent single agents or combinations, capable of effectively eradicating the offending organisms might provide added clinical benefit in the fight against CAD. Further studies are ongoing or planned to evaluate this potential. In the meantime, it is not presently recommended that antimicrobials be routinely prescribed for the secondary prevention of CAD.