Rapid reduction in uric acid by a urate-lowering agent is associated with recurrent cardiovascular events.

<bold>Objectives: </bold>Results from a recent study showed that the risk of cardiovascular and all-cause mortality was higher in patients who received febuxostat, a potent urate-lowering agent, than that in patients who received allopurinol. Therefore, we hypothesized that an abrupt change in serum urate levels caused by urate-lowering agents would influence the risk of cardiovascular events.<bold>Methods: </bold>We included patients with a history of cardiovascular disease (CVD) who received allopurinol or febuxostat. Cardiovascular events were defined as follows: nonfatal myocardial infarction, nonfatal stroke, unstable angina, heart failure, and cardiovascular death. The change in serum urate levels was determined by the difference or reduction rate in urate within 6 months after exposure to allopurinol or febuxostat. The factors associated with cardiovascular events were evaluated by Cox regression analysis.<bold>Results: </bold>In total, 207 patients with CVD who were exposed to allopurinol or febuxostat were included. Cardiovascular events occurred in 38 patients (18.4%). In univariate analysis, age, diabetes mellitus, baseline urate levels, difference in mean urate levels between baseline and post-exposure (Δuratemean), and reduction rate in urate to the lowest post-exposure levels (Δuratelowest/day) were associated with cardiovascular events. Further, results from the multivariate analysis revealed that age [hazard ratio (HR) 1.036, 95% confidence interval (CI), 1.001-1.072, p = 0.042], Δuratemean (HR 1.188, CI, 1.033-1.366, p = 0.015), and Δuratelowest/day (HR 6.963, CI, 2.215-21.886, p = 0.001) were associated with cardiovascular events.<bold>Conclusion: </bold>Rapid reduction in serum urate levels was associated with a higher risk of cardiovascular events. Thus, careful attention should be paid to abruptly changing serum urate levels after treating urate-lowering agent in high-risk CVD patients. [ABSTRACT FROM AUTHOR]