Pharmacotherapy of abdominal aortic aneurysms.
Aortic aneurysms account for 10,000 deaths annually in the UK, due to rupture. At present the only effective therapeutic strategy to treat abdominal aortic aneurysms is to surgically repair them; this carries an elective mortality of up to 10%. Recent advances in vascular biology have led to a greater understanding of the pathophysiological process that causes aortic aneurysms to expand and rupture. Key pathological processes include widespread aortic inflammation, proteolytic degradation of the extracellular matrix, neovascularisation and generation of reactive oxygen species. Identification of these processes has lead to pharmacological strategies to prevent aneurysm expansion and rupture. Many of these strategies have undergone proof of concept in animal models and some have now entered clinical trials. This review outlines current thinking regarding the molecular events leading to aneurysm expansion and explains how these processes may be inhibited. Experimental data on agents retarding aneurysm expansion in animal models are discussed. A significant proportion of the review details pharmacological agents that have undergone or are undergoing clinical trials. Pharmacological treatment for abdominal aneurysms is urgently required given the number of small aneurysms being diagnosed by screening programmes. This is a rapidly evolving field and one in which translation from experimental research to clinical practice is anticipated within 5 years.
Dawson
Joe
J
Department of Vascular Surgery, St. George's, University of London, St. George's Hospital, UK.
Choke
Edward
E
Sayed
Saiqa
S
Cockerill
Gillian
G
Loftus
Ian
I
Thompson
Matt M
MM
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D011480:Protease Inhibitors / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D020533:Angiogenesis Inhibitors; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D011480:Protease Inhibitors