Antibiotic treatment of atherosclerosis.
OBJECTIVE
Several lines of evidence have demonstrated an association between a variety of chronic bacterial infections and atherosclerotic cardiovascular disease. This has led to the proposal that antibiotic therapy might be helpful in the secondary prevention of atherosclerosis. A variety of smaller pilot studies have been reported testing this hypothesis and several large multicenter trials are also underway. The purpose of this review is to summarize the results of these studies and comment on their implications for the treatment of atherosclerosis.


RESULTS
Most of the antibiotic studies to date have been secondary prevention studies that have targeted patients exposed to Chlamydia pneumoniae. Most have used either azithromycin or roxithromycin with treatment courses ranging from a few days to 3 months. Several small studies of coronary artery disease patients have shown significant promise for reducing cardiovascular events such as death, myocardial infarction, or admission for unstable angina. However, other studies have not been so positive. Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders, WIZARD, the largest study to date, in which stable post-myocardial infarction patients were randomized to receive a 3-month course of azithromycin or placebo, demonstrated a significant reduction in death and myocardial infarction by 6 months, but this benefit was not sustained throughout the remaining course of follow-up. The Azithromycin and Coronary Events (ACES) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) trials are ongoing and are testing the effect of more prolonged treatment duration.


CONCLUSIONS
A variety of antibiotic trials for the secondary prevention of atherosclerosis have been performed. Several pilot studies have shown significant positive clinical effects, but, thus far, no large randomized trial has confirmed those findings. Some concerns over the antibiotics chosen and the duration of treatment have been raised. Other trials are underway to address some of those concerns. In the meantime, no recommendation for the use of antibiotic therapy for the secondary prevention of atherosclerosis can yet be made.
Muhlestein
Joseph B
JB
Division of Cardiology, LDS Hospital, 8th Avenue & C Street, Salt Lake City, Utah 84143, USA. ldbmuhle@ihc.com
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D017963:Azithromycin / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control; D023521:Chlamydophila Infections / Q000150:complications; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity; D017291:Clarithromycin / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D023903:Coronary Restenosis / Q000517:prevention & control; D004036:Diet, Atherogenic; D024841:Fluoroquinolones / Q000627:therapeutic use; D000077734:Gatifloxacin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000150:complications / Q000517:prevention & control; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic; D015575:Roxithromycin / Q000627:therapeutic use; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015575:Roxithromycin; D017963:Azithromycin; D002097:C-Reactive Protein; D017291:Clarithromycin; D000077734:Gatifloxacin