title: Allopurinol as a therapeutic option in cardiovascular disease.
abstract: Epidemiological studies indicate that hyperuricaemia is an independent risk factor for cardiovascular disease. Alongside uric acid formation, increased xanthine oxidase activity also results in the formation of oxidative free radicals and superoxide particles. Oxidative stress significantly contributes to the development of cardiovascular disease, including endothelial cell dysfunction, atherosclerosis, vascular calcification and impaired myocardial energetics. Allopurinol, a competitive xanthine oxidase inhibitor, in addition to reducing serum uric acid levels, can act as a free radical scavenger. Although traditionally used for the management of gout, there has been renewed interest in the role of allopurinol in the management of cardiovascular disease. In this review, we summarise the role of the xanthine oxidase pathway in the generation of oxidative stress and evaluate the current body of evidence assessing the clinical effects of allopurinol in patients with cardiovascular disease. A number of small clinical studies have shown a beneficial effect of allopurinol in reducing ischemia-reperfusion injury in the setting of bypass surgery and coronary angioplasty. Additionally, studies in heart failure indicate a potential favourable effect of allopurinol on endothelial dysfunction, LV function and haemodynamic indices, particularly in those with raised serum uric acid levels. Whilst this cheap and readily available pharmacological option may offer a very cost effective therapeutic option, large-scale prospective studies are required to better delineate its role in reducing hard clinical end-points.
authors.affiliation: Heart of England NHS Foundation Trust, Birmingham, United Kingdom.
authors.forename: Osita N
authors.initials: ON
authors.lastname: Okafor
authors.affiliation: East & North Hertfordshire NHS Trust, Hertfordshire, United Kingdom; University of Hertfordshire, Hertfordshire, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Farrington
authors.affiliation: East & North Hertfordshire NHS Trust, Hertfordshire, United Kingdom; University of Hertfordshire, Hertfordshire, United Kingdom; Imperial College, London, United Kingdom. Electronic address: d.gorog@imperial.ac.uk.
authors.forename: Diana A
authors.initials: DA
authors.lastname: Gorog
mesh_terms: D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D033461:Hyperuricemia / Q000150:complications / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase