Antimicrobial Therapy for Coronary Artery Disease
Antimicrobial Therapy for Coronary Artery Disease
ABSTRACT & COMMENTARY
Synopsis: Treatment with roxithromycin was associated with improved outcome in patients with non-Q-wave myocardial infarction or unstable angina.
Source: Gurfinkel E, et al. Randomized trial of roxithro-mycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet 1997;350:404-407.
Gurfinkel and colleagues randomized 202 eligible patients with either unstable angina or non-Q-wave myocardial infarction to receive either roxithromycin, 150 mg bid, or placebo for 30 days. Among the 193 patients who received treatment for at least 72 hours, almost two-thirds of each group completed 30 days; the mean duration of treatment in each group was 24 (±11) days. The two treatment groups were similar at baseline. Approximately one-tenth of each group had non-Q-wave myocardial infarction.
In the intention-to-treat analysis, the occurrence of a "double end point" (death plus myocardial infarction) was 0% in the roxithromycin group and 4% in the placebo group (P = 0.058). The occurrence of a "triple end point" (death, myocardial infarction, and recurrent angina) was 2% in the antibiotic recipients and 9% in those receiving placebo (P = 0.032).
COMMENT BY STAN DERESINSKI, MD, FACP
The issue of the Lancet in which the study by Gurfinkel et appears also contains a review entitled "Chronic infections and coronary heart disease: Is there a link?" (Danesh J, et al. Lancet 1997;350:430-436) and an editorial entitled "Can we treat coronary artery disease with antibiotics?" (Lip GYH, Beevers DG. Lancet 1997;350:378-379). As pointed out in the former article, three organisms in particular have been epidemiologically associated, with greater or lesser robustness, to the occurrence of coronary artery disease: Helicobacter pylori, cytomegalovirus (CMV), and Chlamydia pneumoniae. The story is weakest with Helicobacter, while that of CMV is perhaps the most complete, at least in some settings.
A case-control study has identified CMV seropositivity as a modest risk factor for carotid atherosclerosis (Sorlie PD, et al. J Med Virol 1994;42:33-37; Nieto FJ, et al. Circulation 1996;94:922-927). CMV DNA is present in a high proportion of atherosclerotic plaque, as well as in uninvolved aortic tissue obtained from the same patients (Melnick JL, et al. J Med Virol 1994;42:170-174). CMV has been found to be present in lesions of a subset of patients who develop restenosis after coronary angioplasty. In this setting, an immediate early protein (IE84) produced by CMV binds to and inactivates the tumor suppressor protein (p53) in vascular smooth muscle cells, resulting in excessive proliferation of these cells (Speir E, at al. Science 1994;265:391-394).
The potential role of C. pneumoniae in the pathogenesis of atherosclerotic disease is especially intriguing since this organism is exquisitely susceptible in vitro to a variety of antibiotics, in particular, tetracyclines, quinolones, and macrolides.
C. pneumoniae can replicate in human endothelial cells and aortic smooth muscle cells in vitro (Gaydos CA, et al. Infect Immun 1996;64:1614-1620). C. pneumoniae has been found, by either immunocytochemistry or PCR, in coronary lesions in young adults, but not in their normal-appearing coronary arteries (Kuo CC, et al. Proc Natl Acad Sci USA 1995;92:6911-6914). It has also been identified in carotid artery plaque and in coronary artery plaques and has been recovered in culture from the latter (Jackson LA, et al. J Infect Dis 1997;176:292-295; Grayston JT, et al. Circulation 1995;92:3397-3400; Ramirez JA, et al. Ann Intern Med 1996;125:979-982).
C. pneumoniae has also been identified by immunohistochemical staining in aortic valve tissue of patients with non-rheumatic aortic stenosis (Juvonen J, et al. J Am Coll Cardiol 1997;29:1054-1059).
Thus, although additional evidence is needed before causality can be accepted, both CMV and C. pneumoniae are potential therapeutic targets in patients with arterial disease in the context of clinical trials. The study reviewed here demonstrates an apparent benefit of macrolide therapy in the management of patients with non-Q-wave myocardial infarction or unstable angina. Perhaps the major defect in the study is that the results were not analyzed separately by the presence or absence of seropositivity to C. pneumoniae. Thus, even if roxithromycin is effective in this setting, it is possible that its efficacy has nothing to do with an antimicrobial effect, but rather to the anti-inflammatory effects of macrolides (Agen C, et al. Agents and Actions 1993;38:85-90). Further studies are warranted and are, I am certain, already in progress.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.