Doxycycline Inhibition of Abdominal Aortic Aneurysm Growth - A Systematic Review of the Literature

Benjamin      R. Dodd; Roy      A. Spence

Abstract

Abdominal aortic aneurysm (AAA) is a common disease and a major cause of death through rupture, the risk of which increases with aneurysm size. There is approximately a 5 year interval from when aneurysmal dilatation develops until it reaches a size where surgery is indicated. Slowing, or arresting, aneurysm growth during this period would be beneficial. Aneurysmal aortic wall degeneration is a multifactorial, chronic inflammatory process resulting via activation of matrix metalloproteinases (MMPs), in destruction of mural connective tissue. Doxycycline, a tetracycline antibiotic, is a known inhibitor of MMPs. Animal studies of doxcycline for AAA provide significant evidence of a beneficial effect. However, the human studies, comprising 6 controlled trials and 2 cohort studies, provide conflicting evidence. They are generally of poor methodological quality with small numbers (just 255 subjects analyzed), lack of adjustment for confounding variables, short term doxycycline exposure and a lack of long term follow up. Standardization of dose (per unit weight) and confirmation of compliance remain other systemic failings. The safety of long-term doxycycline use is yet to be proved. The evidence for any beneficial effect of doxycycline as a treatment for AAA, therefore, remains weak. Further studies are required and will ideally be multicentre, involve large subject numbers and be of high quality randomization and blinding with longer periods of doxycycline exposure, confirmation of compliance, standardization of confounding variables and prolonged follow up.

Keywords: Abdominal aortic aneurysm, doxycycline, matrix metalloproteinase, inflammation, angiogenesis, apoptosis, metal chelation, bone metabolism, randomized controlled trial, reverse transcriptase polymerase chain reaction