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

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.

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.

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 (Δurate_mean), and reduction rate in urate to the lowest post-exposure levels (Δurate_lowest/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], Δurate_mean (HR 1.188, CI, 1.033-1.366, p = 0.015), and Δurate_lowest/day (HR 6.963, CI, 2.215-21.886, p = 0.001) were associated with cardiovascular events.

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.