Impact of Allopurinol on Risk of Myocardial Infarction
Impact of Allopurinol on Risk of Myocardial Infarction
Background Gout therapy includes xanthine oxidase inhibitors (XOI) and colchicine, which have both been associated with decreased cardiovascular risk. However, their effects on major cardiac events, such as myocardial infarction (MI), need to be investigated further.
Objectives To investigate whether XOIs and colchicine are associated with decreased risk of MI.
Methods This case-control study compared patients with first-ever MI and matched controls. Cases were recruited from the Pharmacoepidemiological General Research on MI registry. Controls were selected from a referent population (n=8444) from general practice settings.
Results The study sample consisted of 2277 MI patients and 4849 matched controls. Use of allopurinol was reported by 3.1% of cases and 3.8 of controls, and 1.1% of cases and controls used colchicine. The adjusted OR (95% CI) for MI with allopurinol use was 0.80 (0.59 to 1.09). When using less stringent matching criteria that allowed for inclusion of 2593 cases and 5185 controls, the adjusted OR was 0.73 (0.54 to 0.99). Similar results were found on analysis by sex and hypertension status. Colchicine used was not associated with a decreased risk of MI (aOR=1.17 (0.70 to 1.93)).
Conclusions Allopurinol may be associated with a reduced risk of MI. No decreased risk of MI was found in colchicine users. Besides its urate-lowering property, allopurinol might have a cardioprotective effect.
Gout is caused by deposition of monosodium urate crystals in joints after chronic hyperuricaemia. Recent epidemiologic studies have shown an increased prevalence of gout that may be attributed to shifts in diet and lifestyle, improved medical care, and increased longevity.
The disease is strongly associated with several comorbidities and particularly traditional vascular risk factors. Indeed, recent estimates indicate that among individuals with gout, about two-thirds have hypertension, half are obese, one-half have diabetes. Cardiovascular diseases are the greatest threat for patients with gout. Evidence from prospective and interventional studies of various populations suggests that gout and hyperuricaemia are independent risk factors for cardiovascular diseases. Hyperuricaemia and gout are associated with increased risk of myocardial infarction (MI), peripheral artery disease and death primarily due to elevated risk of cardiovascular diseases. The mechanisms linking hyperuricaemia and gout with cardiovascular events are unclear but may include oxidative stress generated by xanthine oxidase (XO), the enzyme that catalyses the formation of urate. Other explanations are a direct contribution to endothelial dysfunction and low-grade inflammation associated with increased urate levels and tophi.
In addition to requiring symptomatic treatment of acute gout attacks, nearly all gout require long-term urate-lowering therapy (ULT). Therefore, knowledge of the effects of these drugs on the cardiovascular system is of major interest. Allopurinol, and the most recent introduced drug, febuxostat, are the sole available XO inhibitors (XOI). In addition to their urate-lowering effects, XOIs may have a beneficial effect on the cardiovascular system by decreasing oxidative stress in the vasculature. Interestingly, colchicine use, for treating acute gout attacks, has been associated with decreased prevalence of MI. To further investigate the impact of ULT and colchicine on MI, we conducted a large case-control study to assess the association of use of these drugs and risk of MI.
Abstract and Introduction
Abstract
Background Gout therapy includes xanthine oxidase inhibitors (XOI) and colchicine, which have both been associated with decreased cardiovascular risk. However, their effects on major cardiac events, such as myocardial infarction (MI), need to be investigated further.
Objectives To investigate whether XOIs and colchicine are associated with decreased risk of MI.
Methods This case-control study compared patients with first-ever MI and matched controls. Cases were recruited from the Pharmacoepidemiological General Research on MI registry. Controls were selected from a referent population (n=8444) from general practice settings.
Results The study sample consisted of 2277 MI patients and 4849 matched controls. Use of allopurinol was reported by 3.1% of cases and 3.8 of controls, and 1.1% of cases and controls used colchicine. The adjusted OR (95% CI) for MI with allopurinol use was 0.80 (0.59 to 1.09). When using less stringent matching criteria that allowed for inclusion of 2593 cases and 5185 controls, the adjusted OR was 0.73 (0.54 to 0.99). Similar results were found on analysis by sex and hypertension status. Colchicine used was not associated with a decreased risk of MI (aOR=1.17 (0.70 to 1.93)).
Conclusions Allopurinol may be associated with a reduced risk of MI. No decreased risk of MI was found in colchicine users. Besides its urate-lowering property, allopurinol might have a cardioprotective effect.
Introduction
Gout is caused by deposition of monosodium urate crystals in joints after chronic hyperuricaemia. Recent epidemiologic studies have shown an increased prevalence of gout that may be attributed to shifts in diet and lifestyle, improved medical care, and increased longevity.
The disease is strongly associated with several comorbidities and particularly traditional vascular risk factors. Indeed, recent estimates indicate that among individuals with gout, about two-thirds have hypertension, half are obese, one-half have diabetes. Cardiovascular diseases are the greatest threat for patients with gout. Evidence from prospective and interventional studies of various populations suggests that gout and hyperuricaemia are independent risk factors for cardiovascular diseases. Hyperuricaemia and gout are associated with increased risk of myocardial infarction (MI), peripheral artery disease and death primarily due to elevated risk of cardiovascular diseases. The mechanisms linking hyperuricaemia and gout with cardiovascular events are unclear but may include oxidative stress generated by xanthine oxidase (XO), the enzyme that catalyses the formation of urate. Other explanations are a direct contribution to endothelial dysfunction and low-grade inflammation associated with increased urate levels and tophi.
In addition to requiring symptomatic treatment of acute gout attacks, nearly all gout require long-term urate-lowering therapy (ULT). Therefore, knowledge of the effects of these drugs on the cardiovascular system is of major interest. Allopurinol, and the most recent introduced drug, febuxostat, are the sole available XO inhibitors (XOI). In addition to their urate-lowering effects, XOIs may have a beneficial effect on the cardiovascular system by decreasing oxidative stress in the vasculature. Interestingly, colchicine use, for treating acute gout attacks, has been associated with decreased prevalence of MI. To further investigate the impact of ULT and colchicine on MI, we conducted a large case-control study to assess the association of use of these drugs and risk of MI.
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