The Effect of Intensive Urate Lowering Therapy (ULT) With Febuxostat in Comparison With Allopurinol on Cardiovascular Risk in Patients With Gout Using Surrogate Markers: a Randomized, Controlled Trial

Detailed Summary

There is a mounting and clear association between hyperuricaemia, gout and the presence of traditional cardiovascular (CV) risk factors and CV event-equivalent conditions such as chronic kidney disease, metabolic syndrome, and diabetes. Gout is associated with increased risk of CV events such as myocardial infarction and CV death. Furthermore hyperuricaemia is clearly associated with an increased arterial stiffness, a marker of pre-clinical atherosclerosis. Carotid-femoral pulse wave velocity (PWV) is the "gold standard" measurement of arterial stiffness and it is considered, in this trial, as a valid surrogate endpoint with clearly established relevance to predict cardiovascular disease (CVD) clinical outcome In this randomised trial conducted on adult subjects with a history of gout, we use surrogate endpoints to investigate the efficacy of febuxostat compared with allopurinol to predict (CVD) clinical outcome. Eligible subjects were randomised in a 1:1 ratio to the following treatment groups: * Test product: febuxostat 80 mg or 120 mg once daily (120 mg daily, if serum urate was \>6 mg/dL after 2 weeks of treatment at 80 mg daily). * Active comparator: allopurinol 100 mg once daily (up to a maximum dose of 600 mg daily escalated in 100 mg increments every 2 weeks, if serum urate acid (sUA) was \>6 mg/dL after 2 weeks of treatment at the previous dose). The study duration was 39 weeks, which included the: * Run-in/screening period: 1 week (extendable up to a maximum of 30 days according to variability of sUA levels); * Treatment period: 36 weeks; * Safety follow-up period: 2 weeks.

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