2000

DOI: 10.1086/315597

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Collaborative Multidisciplinary Workshop Report: Clinical Antimicrobial Trials for Primary and Secondary Prevention of Atherosclerotic Cardiovascular Disease

Joseph B Muhlestein²,

John G. Bartlett³

et al.

Abstract: The task assigned to the working group on Clinical Antimicrobial Trials for Primary and/or Secondary Prevention of Atherosclerotic Cardiovascular Disease was to evaluate the need for additional clinical antibiotic trials of a primary or secondary nature for the treatment of atherosclerotic heart disease and to suggest possible designs for future trials. In addition, the working group was to define the role of collaboration in answering research questions.

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Infection and Atherosclerosis Therapeutic Implications1

Infektion Und Inflammation1

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Cited by 6 publications

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“…However, much more information is required before any recommendation can be made for the standard use of antimicrobial treatment for the treatment of atherosclerosis. [133] The appropriate use of anti-infectives or vaccines in the primary prevention of atherosclerosis has yet to be addressed.…”

Section: Resultsmentioning

confidence: 99%

Secondary Prevention of Coronary Artery Disease with Antimicrobials

¹

2002

American Journal of Cardiovascular Drugs

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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.

“…However, much more information is required before any recommendation can be made for the standard use of antimicrobial treatment for the treatment of atherosclerosis. [133] The appropriate use of anti-infectives or vaccines in the primary prevention of atherosclerosis has yet to be addressed.…”

Section: Resultsmentioning

confidence: 99%

Secondary Prevention of Coronary Artery Disease with Antimicrobials

¹

2002

American Journal of Cardiovascular Drugs

View full text Add to dashboard Cite

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.

“…26,27 Ongoing work is aimed at defining groups of individuals who may benefit from antibiotic therapy, and several large-scale prospective treatment trials are currently underway to determine if antibiotics may help in some patients with coronary artery disease. 28 Since ARMD involves inflammation, with features similar to atherogenesis, the current study examined if ARMD is associated with C pneumoniae infection.…”

Section: Clinical Sciencesmentioning

confidence: 99%

Serological Association Between Chlamydia pneumoniae Infection and Age-Related Macular Degeneration

¹

,

et al. 2003

Arch Ophthalmol

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Background: Age-related macular degeneration (ARMD) is a leading cause of blindness in the United States, but the mechanisms that initiate and promote the disease remain ill defined. There are several risk factors that ARMD shares with atherosclerosis, and these diseases may have similar pathogenic mechanisms that involve inflammation. Chlamydia pneumoniae, a prokaryotic pathogen that causes chronic inflammation is now emerging as a risk factor in the development of cardiovascular diseases. It is therefore plausible that this microorganism also contributes to the pathogenesis of ARMD. Methods: To examine if C pneumoniae infection is associated with ARMD, serum samples from 25 consecutive patients with ARMD and from 18 without the disease were collected and assayed for the presence of the antibodies to C pneumoniae elementary bodies, Chla-mydia trachomatis heat shock protein 60 (cHsp60), C trachomatis heat shock protein 10 (cHsp10), Escherichia coli GroEL, and E coli GroES. Results: A serological association was found between ARMD and anti-C pneumoniae antibodies (P =.047) but not between ARMD and the anti-C trachomatis or anti-E coli heat shock protein antibodies. The association remained statistically significant after adjusting for age and smoking, both established risk factors for ARMD. Conclusions: These data indicate that C pneumoniae infection may be associated with ARMD. Further studies on larger cohorts of individuals are necessary to determine if this pathogen plays a role in the pathogenesis of ARMD.

“…At 6 months, the secondary endpoint of death/MI was reduced and the reduction in the full composite endpoint was almost significant, but the differences between treatment groups gradually diminished. The Azithromycin and Coronary Events Study (ACES), sponsored by the National Institute of Health, studied 4012 adults with documented stable coronary artery disease [165]. Patients were recruited from 256 clinical centers in United States between 1999 and 2000 and were randomised to treatment with oral azithromycin 600mg once a week for a year.…”

Section: Infection and Atherosclerosis Therapeutic Implicationsmentioning

confidence: 99%

Infections and Atheromatous Plaque: Current Therapeutic Implications

2013

Current Pharmaceutical Design

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Infections are the most common inflammatory triggers and acute and chronic infections have been associated with the development and progression of atherosclerotic disease raising interest in the infectious hypothesis of atherosclerosis. Pathogens have been identified in atherosclerotic plaques and large epidemiological studies have documented conflicting associations between serological evidence of infection and cardiovascular events. Influenza A was mostly studied as a trigger for cardiovascular events during winter months, whilst cytomegalovirus, Chlamydia pneumoniae, helicobacter pylori and porphyromonas ginigivalis were the most studied chronic pathogens which had been associated with the development and progression of cardiovascular disease. Infectious agents can contribute to atherosclerosis by having a direct effect on the vascular wall or via indirect effects including inflammatory responses and molecular mimicry. Efforts to prevent infection with vaccination or treat specific infectious agents with antibiotics have provided mostly negative results, thereby challenging the validity of the infectious hypothesis of atherosclerosis.

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