HPE Grunenthal handbook - Page 18

CVD were increased by approximately 30% among subjects with gout compared with healthy controls (10.3 per 1000 person-years vs 8.0 per 1000 person- years). The results from the MRFIT study have been confirmed by those of another large observational survey, the Third National Health and Nutrition Examination Survey (NHANES III), 9 which assessed the association between gout and cardiovascular mortality in the US population. The multivariable risk of CV mortality was increased by 46% in those with gout compared with those without gout (95% CI 1.07–2.00). A further large-scale observational study investigated the relation between a self- reported history of gout and the risk of death and MI in 51,297 males with and without history of CHD and participants of the Health Professionals Follow-Up for CVD (1.38; 95% CI 1.15–1.66) and CHD (1.55; 95% CI 1.24–1.93) despite an extensive adjustment including almost all the possible confounding risk and dietary factors. The relative risk of cardiovascular events was largely comparable and highly significant in patients regardless of the history of CHD. Finally, comparable results have been reported by another study where a 39% increase in the relative risk of MI was also reported in women with gout (95% CI 1.20–1.61) compared with controls. 19 The evidence reported by of all these studies suggest the generalisability of the observational data to a large population of patients with gout that must be considered at a very high- risk and subject to a careful evaluation of early CV involvement in addition to control of serum urate levels and well-known CV risk factors. The association between gout and cardiovascular mortality and morbidity has been specifically investigated in the Asian population, and reports very similar results. Teng and colleagues 20 assessed the link between gout and CHD mortality in a prospective cohort of the Singapore Chinese Health Study. In agreement with previous observations, subjects with gout had a higher risk of CHD death (hazard ratio (HR) 1.38; 95% CI 1.10–1.73) compared with subjects without gout. The association was significant in males and females, but the risk estimates for women were higher (HR 1.71; 95% CI 1.12–2.60), probably because of the age range of the population (45–74 years) including pre-menopausal subjects. A significant increase in the relative risk of CVD mortality was also observed in a large sample of the gout population of Taiwan compared with normo-uricaemic controls (HR 1.97; 95% CI 1.08–3.59). 21 Another study of individuals in Taiwan 22 found similar results in terms of CVD mortality among the individuals with gout (HR 1.10: 95% CI 1.07–1.13) with a large relative risk (RR) in patients with normal renal function, thereby excluding the involvement of renal disease in the association between hyperuricemia and cardiovascular disease. Gout and heart failure Heart failure is a growing global epidemic but particularly in industrialised countries. Prevention and treatment of heart failure is one of the most important targets of CV treatment and this implies the correct management of all the possible risk factors including serum uric acid and gout. Heart failure is typically associated with an over-expression of xanthine oxidase that could be responsible for an increased production of uric acid that can largely contribute to the prevalence of hyperuricaemia and gout in patients with left ventricular dysfunction regardless of deterioration of renal function. 23 An association between high levels of urate and heart Table 1 Summary of randomised clinical trials in the field of urate-lowering treatment and cardiovascular disease CV field Intervention Primary outcomes ClinicalTrials.gov/status Blood pressure (BP) control Febuxostat vs allopurinol Clinic BP and ambulatory blood pressure monitoring (ABPM) NCT0171622; terminated (unable to enroll participants) Coronary endothelial dysfunction Febuxostat vs placebo Coronary flow NCT01763996; completed BP control Febuxostat vs placebo ABPM NCT01496469; completed Exercise tolerance in chronic angina Febuxostat vs placebo Exercise tolerance testing (ETT) NCT01549977; terminated Vascular structure and function (FORWARD) Febuxostat vs allopurinol Carotid–femoral pulse wave velocity EudraCT 2014-5567-33 enrollment closed New-onset metabolic syndrome (FAST) Febuxostat vs placebo Insulin resistance and features of metabolic syndrome NCT01654276; ongoing BP and cardiovascular (CV) complications (CARES) Febuxostat vs allopurinol MACE NCT01101035; ongoing Treatment of coronary heart disease (ALL-HEARTY) Allopurinol vs placebo MACE EudraCT 2013-003559-39 Cerebrovascular protection (XILO-FIST) Allopurinol vs placebo White matter protection NCT0212218; starting recruitment Major CV disease (FREED) Febuxostat vs placebo MACE NCT01984749; ongoing 18 | 2018 | hospitalpharmacyeurope.com